Melanoma

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In the fall of 2020, Hassane M. Zarour, MD, and colleagues began to pore over raw data from their phase 1 clinical trial designed to determine if fecal microbiota transplantation (FMT) could reprogram the gut microbiome in advanced melanoma patients who failed to respond to anti–programmed death 1immunotherapy.

Preclinical mouse studies have demonstrated that the gut microbiota could influence the response of tumors to anti–PD-1 immunotherapy, but FMT had not been previously evaluated in human patients with malignant melanoma whose disease persisted or progressed after medical therapy. Only 30%-40% of melanoma patients respond to anti–PD-1 immunotherapy, so the researchers’ sense of anticipation was palpable. “It’s a high-risk, high-reward study, so you never know,” Dr. Zarour, a dermatologist and immunologist who is coleader of the melanoma program at the University of Pittsburgh Medical Center’s Hillman Cancer Center, said in an interview.

For the study, which was funded by the National Institutes of Health and published in Science, Dr. Zarour and a team of colleagues, including Diwakar Davar, MD, a medical oncologist/hematologist at UPMC and Giorgio Trinchieri, MD, head of the cancer immunology section at the National Cancer Institute, enrolled 16 patients with advanced melanoma whose disease had persisted or progressed with anti-PD-1 drugs; donors were 7 patients with advanced melanoma who had responded to pembrolizumab, 4 with a complete response and 3 with a partial response, with a median progression-free survival of 56 months.

After donors and patients underwent serial stool sampling and studies to stamp out the potential for transmitting infectious agents, the researchers administered the donor-derived FMT to patients via colonoscopy every 14 days for 3 weeks, followed by pembrolizumab. To their delight, 6 of the 15 evaluable recipients responded to treatment, with a reduction in tumor or long-term disease stabilization. Moreover, responders also showed increased abundance of taxa that were previously associated with response to immunotherapy, increased activation of CD8+ T cells, and decreased frequency of interleukin-8–expressing myeloid cells.

“This opens new doors for the future,” Dr. Zarour said. “It’s very encouraging, but I don’t want to overstate the data. It’s a small, nonrandomized trial, but one has to keep in mind that people were skeptical about this work; they didn’t think FMT would work. Now we see many people coming into the field to investigate the role of the microbiome as a therapeutic tool, which is great.”

Teri Greiling, MD, characterized the finding as a key development in understanding the microbiome’s potential to influence the course of melanoma and other diseases. “What’s emerging over the last decade of research is that our immune system has a close, back-and-forth relationship with our microbiota,” said Dr. Greiling, associate professor of dermatology at Oregon Health & Science University, Portland. “From day 1 of birth, we’re colonized by microbes that train our immune system how to function. In response, your immune system keeps those microbes in check and shapes which ones are allowed to colonize, and which ones are a target for attack. Thus, inflammatory responses are generated. Similarly, the goal of immunotherapy is to activate the immune system to fight cancer. This study shows that the immune system continues to need the colonizing microbes in our body to function optimally.”

Immunotherapy with checkpoint inhibitors was not an option for malignant melanoma patients until 2011, she noted, so the potential for FMT to further improve outcomes is welcome news for patients and their families. “We went from a less than 5% chance of survival with metastatic melanoma to now, with the right combination of checkpoint inhibitors, we’re up over 50%, which is amazing in a decade,” Dr. Greiling said. “Still, we’re losing half of our patients. If [FMT provides] a 30% improvement over that, that would be great, but it’s hard to extrapolate from such small numbers.”
 

Positive results in an Israeli study

Results from a similar, smaller phase 1 trial of 2 FMT donors and 10 recipients with metastatic melanoma who had progressed on anti-PD-1 therapy, from the Ella Lemelbaum Institute for Immuno-Oncology at Sheba Medical Center in Tel HaShomer, Israel, yielded similar results. The FMT protocol in this study included colonoscopy and oral stool capsules, followed by the reintroduction of anti–PD-1 therapy with nivolumab. The two FMT donors had previously been treated with anti–PD-1 monotherapy for metastatic melanoma and had achieved a clinical response for at least 1 year. Of the 10 FMT recipients, 1 had a complete response and 2 had a partial response.

“We expected changes in the immune system but did not expect that 3 out of the 10 patients in our study would be turned from nonresponders to responders,” the study’s lead author, Erez N. Baruch, MD, PhD, told this news organization. “Since this was a first-in-human study, we were aiming to assess safety and not clinical responses. [We found] that microbiota modulation can change the immune infiltration within melanoma tumors and by this affect response to immunotherapy.”

Dr. Baruch, an internal medicine resident in the physician-scientist track program at the University of Texas, Houston, said that the findings create a potential new therapeutic paradigm, or a new “playing ground” for drug development that can support existing immunotherapies. “It is important for dermatologists to understand that disruptions of the gut microbiota, mainly by antibiotics, may be harmful to melanoma patients,” he said. “Antibiotics in cancer patients should be used judiciously but of course should not be avoided when there’s an indication.”

As for next steps, Dr. Zarour and colleagues are recruiting more patients to boost their sample size and conducting sequential analysis of the microbiome of study participants “to better determine what the good and bad bugs are,” he said. “There are so many variables, including diet and geography. We need more data.” The hope is to develop a “microbiome signature” to identify patients likely to respond to FMT, and maybe one day, a probiotic capsule that patients take to optimize their response to immunotherapy.

“We don’t want to say that the microbiome is responsible for everything, but it’s responsible for some of the response and some of the resistance to treatment,” Dr. Zarour said. “So, we want to identify what candidate nonresponders are more likely to respond to FMT and be able to stick the right stool in the donor. This goes to better education of the microbiome signature. We are working hard on that.”

Dr. Baruch added that performing FMT for melanoma patients requires tight collaborations between oncologists, dermatologists, GI, and infectious disease experts. “These usually can be done in the setting of large cancer centers and will probably not be available in any hospital,” he said. “This is why understanding the mechanisms and developing an FMT-like drug is important. We are focusing on studying the mechanisms behind the clinical effect in order to develop a drug with an FMT-like effect without the safety and logistic issues related to FMTs.”

Studies raise more questions

In the opinion of Dr. Greiling, results from these two studies raise more questions than they answer. “The big question ... is why and how does FMT work, and how can we make the response better?” she said. “Is there one particular gene product from one microbe that is the key magic ingredient, and we can harness this as a drug? More likely it’s a complex interplay between multiple bacterial species needed to direct the immune response. Is there a group of microbes that is the same from person to person, or is it more complex?”

Then there are pending regulatory concerns. “We know that FMT works for [Clostridioides] difficile colitis but it’s not officially [Food and Drug Administration] approved,” Dr. Greiling said. “The FDA is really struggling with how to approve or regulate using bacteria as a drug. Where is that crossover? That inhibits things moving forward, for good reason. You want to balance safety with live microbes.”

The UPMC clinical trial was supported by Merck. Dr. Zarour disclosed that he is supported by grants from the National Cancer Institute and the James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research at UPMC. The Israeli study was funded by the Ella Lemelbaum Institute for Immuno-Oncology. Dr. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research. Dr. Greiling and Dr. Harris-Tryon reported having no relevant financial disclosures.

dbrunk@mdedge.com

In the fall of 2020, Hassane M. Zarour, MD, and colleagues began to pore over raw data from their phase 1 clinical trial designed to determine if fecal microbiota transplantation (FMT) could reprogram the gut microbiome in advanced melanoma patients who failed to respond to anti–programmed death 1immunotherapy.

Preclinical mouse studies have demonstrated that the gut microbiota could influence the response of tumors to anti–PD-1 immunotherapy, but FMT had not been previously evaluated in human patients with malignant melanoma whose disease persisted or progressed after medical therapy. Only 30%-40% of melanoma patients respond to anti–PD-1 immunotherapy, so the researchers’ sense of anticipation was palpable. “It’s a high-risk, high-reward study, so you never know,” Dr. Zarour, a dermatologist and immunologist who is coleader of the melanoma program at the University of Pittsburgh Medical Center’s Hillman Cancer Center, said in an interview.

For the study, which was funded by the National Institutes of Health and published in Science, Dr. Zarour and a team of colleagues, including Diwakar Davar, MD, a medical oncologist/hematologist at UPMC and Giorgio Trinchieri, MD, head of the cancer immunology section at the National Cancer Institute, enrolled 16 patients with advanced melanoma whose disease had persisted or progressed with anti-PD-1 drugs; donors were 7 patients with advanced melanoma who had responded to pembrolizumab, 4 with a complete response and 3 with a partial response, with a median progression-free survival of 56 months.

After donors and patients underwent serial stool sampling and studies to stamp out the potential for transmitting infectious agents, the researchers administered the donor-derived FMT to patients via colonoscopy every 14 days for 3 weeks, followed by pembrolizumab. To their delight, 6 of the 15 evaluable recipients responded to treatment, with a reduction in tumor or long-term disease stabilization. Moreover, responders also showed increased abundance of taxa that were previously associated with response to immunotherapy, increased activation of CD8+ T cells, and decreased frequency of interleukin-8–expressing myeloid cells.

“This opens new doors for the future,” Dr. Zarour said. “It’s very encouraging, but I don’t want to overstate the data. It’s a small, nonrandomized trial, but one has to keep in mind that people were skeptical about this work; they didn’t think FMT would work. Now we see many people coming into the field to investigate the role of the microbiome as a therapeutic tool, which is great.”

Teri Greiling, MD, characterized the finding as a key development in understanding the microbiome’s potential to influence the course of melanoma and other diseases. “What’s emerging over the last decade of research is that our immune system has a close, back-and-forth relationship with our microbiota,” said Dr. Greiling, associate professor of dermatology at Oregon Health & Science University, Portland. “From day 1 of birth, we’re colonized by microbes that train our immune system how to function. In response, your immune system keeps those microbes in check and shapes which ones are allowed to colonize, and which ones are a target for attack. Thus, inflammatory responses are generated. Similarly, the goal of immunotherapy is to activate the immune system to fight cancer. This study shows that the immune system continues to need the colonizing microbes in our body to function optimally.”

Immunotherapy with checkpoint inhibitors was not an option for malignant melanoma patients until 2011, she noted, so the potential for FMT to further improve outcomes is welcome news for patients and their families. “We went from a less than 5% chance of survival with metastatic melanoma to now, with the right combination of checkpoint inhibitors, we’re up over 50%, which is amazing in a decade,” Dr. Greiling said. “Still, we’re losing half of our patients. If [FMT provides] a 30% improvement over that, that would be great, but it’s hard to extrapolate from such small numbers.”
 

Positive results in an Israeli study

Results from a similar, smaller phase 1 trial of 2 FMT donors and 10 recipients with metastatic melanoma who had progressed on anti-PD-1 therapy, from the Ella Lemelbaum Institute for Immuno-Oncology at Sheba Medical Center in Tel HaShomer, Israel, yielded similar results. The FMT protocol in this study included colonoscopy and oral stool capsules, followed by the reintroduction of anti–PD-1 therapy with nivolumab. The two FMT donors had previously been treated with anti–PD-1 monotherapy for metastatic melanoma and had achieved a clinical response for at least 1 year. Of the 10 FMT recipients, 1 had a complete response and 2 had a partial response.

“We expected changes in the immune system but did not expect that 3 out of the 10 patients in our study would be turned from nonresponders to responders,” the study’s lead author, Erez N. Baruch, MD, PhD, told this news organization. “Since this was a first-in-human study, we were aiming to assess safety and not clinical responses. [We found] that microbiota modulation can change the immune infiltration within melanoma tumors and by this affect response to immunotherapy.”

Dr. Baruch, an internal medicine resident in the physician-scientist track program at the University of Texas, Houston, said that the findings create a potential new therapeutic paradigm, or a new “playing ground” for drug development that can support existing immunotherapies. “It is important for dermatologists to understand that disruptions of the gut microbiota, mainly by antibiotics, may be harmful to melanoma patients,” he said. “Antibiotics in cancer patients should be used judiciously but of course should not be avoided when there’s an indication.”

As for next steps, Dr. Zarour and colleagues are recruiting more patients to boost their sample size and conducting sequential analysis of the microbiome of study participants “to better determine what the good and bad bugs are,” he said. “There are so many variables, including diet and geography. We need more data.” The hope is to develop a “microbiome signature” to identify patients likely to respond to FMT, and maybe one day, a probiotic capsule that patients take to optimize their response to immunotherapy.

“We don’t want to say that the microbiome is responsible for everything, but it’s responsible for some of the response and some of the resistance to treatment,” Dr. Zarour said. “So, we want to identify what candidate nonresponders are more likely to respond to FMT and be able to stick the right stool in the donor. This goes to better education of the microbiome signature. We are working hard on that.”

Dr. Baruch added that performing FMT for melanoma patients requires tight collaborations between oncologists, dermatologists, GI, and infectious disease experts. “These usually can be done in the setting of large cancer centers and will probably not be available in any hospital,” he said. “This is why understanding the mechanisms and developing an FMT-like drug is important. We are focusing on studying the mechanisms behind the clinical effect in order to develop a drug with an FMT-like effect without the safety and logistic issues related to FMTs.”

Studies raise more questions

In the opinion of Dr. Greiling, results from these two studies raise more questions than they answer. “The big question ... is why and how does FMT work, and how can we make the response better?” she said. “Is there one particular gene product from one microbe that is the key magic ingredient, and we can harness this as a drug? More likely it’s a complex interplay between multiple bacterial species needed to direct the immune response. Is there a group of microbes that is the same from person to person, or is it more complex?”

Then there are pending regulatory concerns. “We know that FMT works for [Clostridioides] difficile colitis but it’s not officially [Food and Drug Administration] approved,” Dr. Greiling said. “The FDA is really struggling with how to approve or regulate using bacteria as a drug. Where is that crossover? That inhibits things moving forward, for good reason. You want to balance safety with live microbes.”

The UPMC clinical trial was supported by Merck. Dr. Zarour disclosed that he is supported by grants from the National Cancer Institute and the James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research at UPMC. The Israeli study was funded by the Ella Lemelbaum Institute for Immuno-Oncology. Dr. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research. Dr. Greiling and Dr. Harris-Tryon reported having no relevant financial disclosures.

dbrunk@mdedge.com

In the fall of 2020, Hassane M. Zarour, MD, and colleagues began to pore over raw data from their phase 1 clinical trial designed to determine if fecal microbiota transplantation (FMT) could reprogram the gut microbiome in advanced melanoma patients who failed to respond to anti–programmed death 1immunotherapy.

Preclinical mouse studies have demonstrated that the gut microbiota could influence the response of tumors to anti–PD-1 immunotherapy, but FMT had not been previously evaluated in human patients with malignant melanoma whose disease persisted or progressed after medical therapy. Only 30%-40% of melanoma patients respond to anti–PD-1 immunotherapy, so the researchers’ sense of anticipation was palpable. “It’s a high-risk, high-reward study, so you never know,” Dr. Zarour, a dermatologist and immunologist who is coleader of the melanoma program at the University of Pittsburgh Medical Center’s Hillman Cancer Center, said in an interview.

For the study, which was funded by the National Institutes of Health and published in Science, Dr. Zarour and a team of colleagues, including Diwakar Davar, MD, a medical oncologist/hematologist at UPMC and Giorgio Trinchieri, MD, head of the cancer immunology section at the National Cancer Institute, enrolled 16 patients with advanced melanoma whose disease had persisted or progressed with anti-PD-1 drugs; donors were 7 patients with advanced melanoma who had responded to pembrolizumab, 4 with a complete response and 3 with a partial response, with a median progression-free survival of 56 months.

After donors and patients underwent serial stool sampling and studies to stamp out the potential for transmitting infectious agents, the researchers administered the donor-derived FMT to patients via colonoscopy every 14 days for 3 weeks, followed by pembrolizumab. To their delight, 6 of the 15 evaluable recipients responded to treatment, with a reduction in tumor or long-term disease stabilization. Moreover, responders also showed increased abundance of taxa that were previously associated with response to immunotherapy, increased activation of CD8+ T cells, and decreased frequency of interleukin-8–expressing myeloid cells.

“This opens new doors for the future,” Dr. Zarour said. “It’s very encouraging, but I don’t want to overstate the data. It’s a small, nonrandomized trial, but one has to keep in mind that people were skeptical about this work; they didn’t think FMT would work. Now we see many people coming into the field to investigate the role of the microbiome as a therapeutic tool, which is great.”

Teri Greiling, MD, characterized the finding as a key development in understanding the microbiome’s potential to influence the course of melanoma and other diseases. “What’s emerging over the last decade of research is that our immune system has a close, back-and-forth relationship with our microbiota,” said Dr. Greiling, associate professor of dermatology at Oregon Health & Science University, Portland. “From day 1 of birth, we’re colonized by microbes that train our immune system how to function. In response, your immune system keeps those microbes in check and shapes which ones are allowed to colonize, and which ones are a target for attack. Thus, inflammatory responses are generated. Similarly, the goal of immunotherapy is to activate the immune system to fight cancer. This study shows that the immune system continues to need the colonizing microbes in our body to function optimally.”

Immunotherapy with checkpoint inhibitors was not an option for malignant melanoma patients until 2011, she noted, so the potential for FMT to further improve outcomes is welcome news for patients and their families. “We went from a less than 5% chance of survival with metastatic melanoma to now, with the right combination of checkpoint inhibitors, we’re up over 50%, which is amazing in a decade,” Dr. Greiling said. “Still, we’re losing half of our patients. If [FMT provides] a 30% improvement over that, that would be great, but it’s hard to extrapolate from such small numbers.”
 

Positive results in an Israeli study

Results from a similar, smaller phase 1 trial of 2 FMT donors and 10 recipients with metastatic melanoma who had progressed on anti-PD-1 therapy, from the Ella Lemelbaum Institute for Immuno-Oncology at Sheba Medical Center in Tel HaShomer, Israel, yielded similar results. The FMT protocol in this study included colonoscopy and oral stool capsules, followed by the reintroduction of anti–PD-1 therapy with nivolumab. The two FMT donors had previously been treated with anti–PD-1 monotherapy for metastatic melanoma and had achieved a clinical response for at least 1 year. Of the 10 FMT recipients, 1 had a complete response and 2 had a partial response.

“We expected changes in the immune system but did not expect that 3 out of the 10 patients in our study would be turned from nonresponders to responders,” the study’s lead author, Erez N. Baruch, MD, PhD, told this news organization. “Since this was a first-in-human study, we were aiming to assess safety and not clinical responses. [We found] that microbiota modulation can change the immune infiltration within melanoma tumors and by this affect response to immunotherapy.”

Dr. Baruch, an internal medicine resident in the physician-scientist track program at the University of Texas, Houston, said that the findings create a potential new therapeutic paradigm, or a new “playing ground” for drug development that can support existing immunotherapies. “It is important for dermatologists to understand that disruptions of the gut microbiota, mainly by antibiotics, may be harmful to melanoma patients,” he said. “Antibiotics in cancer patients should be used judiciously but of course should not be avoided when there’s an indication.”

As for next steps, Dr. Zarour and colleagues are recruiting more patients to boost their sample size and conducting sequential analysis of the microbiome of study participants “to better determine what the good and bad bugs are,” he said. “There are so many variables, including diet and geography. We need more data.” The hope is to develop a “microbiome signature” to identify patients likely to respond to FMT, and maybe one day, a probiotic capsule that patients take to optimize their response to immunotherapy.

“We don’t want to say that the microbiome is responsible for everything, but it’s responsible for some of the response and some of the resistance to treatment,” Dr. Zarour said. “So, we want to identify what candidate nonresponders are more likely to respond to FMT and be able to stick the right stool in the donor. This goes to better education of the microbiome signature. We are working hard on that.”

Dr. Baruch added that performing FMT for melanoma patients requires tight collaborations between oncologists, dermatologists, GI, and infectious disease experts. “These usually can be done in the setting of large cancer centers and will probably not be available in any hospital,” he said. “This is why understanding the mechanisms and developing an FMT-like drug is important. We are focusing on studying the mechanisms behind the clinical effect in order to develop a drug with an FMT-like effect without the safety and logistic issues related to FMTs.”

Studies raise more questions

In the opinion of Dr. Greiling, results from these two studies raise more questions than they answer. “The big question ... is why and how does FMT work, and how can we make the response better?” she said. “Is there one particular gene product from one microbe that is the key magic ingredient, and we can harness this as a drug? More likely it’s a complex interplay between multiple bacterial species needed to direct the immune response. Is there a group of microbes that is the same from person to person, or is it more complex?”

Then there are pending regulatory concerns. “We know that FMT works for [Clostridioides] difficile colitis but it’s not officially [Food and Drug Administration] approved,” Dr. Greiling said. “The FDA is really struggling with how to approve or regulate using bacteria as a drug. Where is that crossover? That inhibits things moving forward, for good reason. You want to balance safety with live microbes.”

The UPMC clinical trial was supported by Merck. Dr. Zarour disclosed that he is supported by grants from the National Cancer Institute and the James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research at UPMC. The Israeli study was funded by the Ella Lemelbaum Institute for Immuno-Oncology. Dr. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research. Dr. Greiling and Dr. Harris-Tryon reported having no relevant financial disclosures.

dbrunk@mdedge.com

A ccording to the US Census Bureau, more than half of all Americans are projected to belong to a minority group, defined as any group other than non-Hispanic White alone, by 2044. ¹ Consequently, the United States rapidly is becoming a country in which the majority of citizens will have skin of color. Individuals with skin of color are of diverse ethnic backgrounds and include people of African, Latin American, Native American, Pacific Islander, and Asian descent, as well as interethnic backgrounds. ² Throughout the country, dermatologists along with primary care practitioners may be confronted with certain cutaneous conditions that have varying disease presentations or processes in patients with skin of color. It also is important to note that racial categories are socially rather than biologically constructed, and the term skin of color includes a wide variety of diverse skin types. Nevertheless, the current literature thoroughly supports unique pathophysiologic differences in skin of color as well as variations in disease manifestation compared to White patients. ^3-5 For example, the increased lability of melanosomes in skin of color patients, which increases their risk for postinflammatory hyperpigmentation, has been well documented. ^5-7 There are various dermatologic conditions that also occur with higher frequency and manifest uniquely in people with darker, more pigmented skin, ^7-9 and dermatologists, along with primary care physicians, should feel prepared to recognize and address them.

Extensive evidence also indicates that there are unique aspects to consider while managing certain skin diseases in patients with skin of color.^8,10,11 Consequently, as noted on the Skin of Color Society (SOCS) website, “[a]n increase in the body of dermatological literature concerning skin of color as well as the advancement of both basic science and clinical investigational research is necessary to meet the needs of the expanding skin of color population.”² In the meantime, current knowledge regarding cutaneous conditions that diversely or disproportionately affect skin of color should be actively disseminated to physicians in training. Although patients with skin of color should always have access to comprehensive care and knowledgeable practitioners, the current changes in national and regional demographics further underscore the need for a more thorough understanding of skin of color with regard to disease pathogenesis, diagnosis, and treatment.

Several studies have found that medical students in the United States are minimally exposed to dermatology in general compared to other clinical specialties,^12-14 which can easily lead to the underrecognition of disorders that may uniquely or disproportionately affect individuals with pigmented skin. Recent data showed that medical schools typically required fewer than 10 hours of dermatology instruction,¹² and on average, dermatologic training made up less than 1% of a medical student’s undergraduate medical education.^13,15,16 Consequently, less than 40% of primary care residents felt that their medical school curriculum adequately prepared them to manage common skin conditions.¹⁴ Although not all physicians should be expected to fully grasp the complexities of skin of color and its diagnostic and therapeutic implications, both practicing and training dermatologists have acknowledged a lack of exposure to skin of color. In one study, approximately 47% of dermatologists and dermatology residents reported that their medical training (medical school and/or residency) was inadequate in training them on skin conditions in Black patients. Furthermore, many who felt their training was lacking in skin of color identified the need for greater exposure to Black patients and training materials.¹⁵ The absence of comprehensive medical education regarding skin of color ultimately can be a disadvantage for both practitioners and patients, resulting in poorer outcomes. Furthermore, underrepresentation of skin of color may persist beyond undergraduate and graduate medical education. There also is evidence to suggest that noninclusion of skin of color pervades foundational dermatologic educational resources, including commonly used textbooks as well as continuing medical education disseminated at national conferences and meetings.¹⁷ Taken together, these findings highlight the need for more diverse and representative exposure to skin of color throughout medical training, which begins with a diverse inclusive undergraduate medical education in dermatology.

The objective of this study was to determine if the preclinical dermatology curriculum at 3 US medical schools provided adequate representation of skin of color patients in their didactic presentation slides.

Methods

Participants—Three US medical schools, a blend of private and public medical schools located across different geographic boundaries, agreed to participate in the study. All 3 institutions were current members of the American Medical Association (AMA) Accelerating Change in Medical Education consortium, whose primary goal is to create the medical school of the future and transform physician training.¹⁸ All 32 member institutions of the AMA consortium were contacted to request their participation in the study. As part of the consortium, these institutions have vowed to collectively work to develop and share the best models for educational advancement to improve care for patients, populations, and communities¹⁸ and would expectedly provide a more racially and ethnically inclusive curriculum than an institution not accountable to a group dedicated to identifying the best ways to deliver care for increasingly diverse communities.

Data Collection—Lectures were included if they were presented during dermatology preclinical courses in the 2015 to 2016 academic year. An uninvolved third party removed the names and identities of instructors to preserve anonymity. Two independent coders from different institutions extracted the data—lecture title, total number of clinical and histologic images, and number of skin of color images—from each of the anonymized lectures using a standardized coding form. We documented differences in skin of color noted in lectures and the disease context for the discussed differences, such as variations in clinical presentation, disease process, epidemiology/risk, and treatment between different skin phenotypes or ethnic groups. Photographs in which the coders were unable to differentiate whether the patient had skin of color were designated as indeterminate or unclear. Photographs appearing to represent Fitzpatrick skin types IV, V, and VI¹⁹ were categorically designated as skin of color, and those appearing to represent Fitzpatrick skin types I and II were described as not skin of color; however, images appearing to represent Fitzpatrick skin type III often were classified as not skin of color or indeterminate and occasionally skin of color. The Figure shows examples of images classified as skin of color, indeterminate, and not skin of color. Photographs often were classified as indeterminate due to poor lighting, close-up view photographs, or highlighted pathology obscuring the surrounding skin. We excluded duplicate photographs and histologic images from the analyses.

We also reviewed 19 conditions previously highlighted by the SOCS as areas of importance to skin of color patients.²⁰ The coders tracked how many of these conditions were noted in each lecture. Duplicate discussion of these conditions was not included in the analyses. Any discrepancies between coders were resolved through additional slide review and discussion. The final coded data with the agreed upon changes were used for statistical analyses. Recent national demographic data from the US Census Bureau in 2019 describe approximately 39.9% of the population as belonging to racial/ethnic groups other than non-Hispanic/Latinx White.²¹ Consequently, the standard for adequate representation for skin of color photographs was set at 35% for the purpose of this study.

 

 

Results

Across all 3 institutions included in the study, the proportion of the total number of clinical photographs showing skin of color was 16% (290/1812). Eight percent of the total photographs (145/1812) were noted to be indeterminate (Table). For institution 1, 23.6% of photographs (155/658) showed skin of color, and 12.6% (83/658) were indeterminate. For institution 2, 13.1% (76/578) showed skin of color and 7.8% (45/578) were indeterminate. For institution 3, 10.2% (59/576) showed skin of color and 3% (17/576) were indeterminate.

Institutions 1, 2, and 3 had 18, 8, and 17 total dermatology lectures, respectively. Of the 19 conditions designated as areas of importance to skin of color patients by the SOCS, 16 (84.2%) were discussed by institution 1, 11 (57.9%) by institution 2, and 9 (47.4%) by institution 3 (eTable 1). Institution 3 did not include photographs of skin of color patients in its acne, psoriasis, or cutaneous malignancy lectures. Institution 1 also did not include any skin of color patients in its malignancy lecture. Lectures that focused on pigmentary disorders, atopic dermatitis, infectious conditions, and benign cutaneous neoplasms were more likely to display photographs of skin of color patients; for example, lectures that discussed infectious conditions, such as superficial mycoses, herpes viruses, human papillomavirus, syphilis, and atypical mycobacterial infections, were consistently among those with higher proportions of photographs of skin of color patients.

Throughout the entire preclinical dermatology course at all 3 institutions, of 2945 lecture slides, only 24 (0.8%) unique differences were noted between skin color and non–skin of color patients, with 10 total differences noted by institution 1, 6 by institution 2, and 8 by institution 3 (Table). The majority of these differences (19/24) were related to epidemiologic differences in prevalence among varying racial/ethnic groups, with only 5 instances highlighting differences in clinical presentation. There was only a single instance that elaborated on the underlying pathophysiologic mechanisms of the discussed difference. Of all 24 unique differences discussed, 8 were related to skin cancer, 3 were related to dermatitis, and 2 were related to the difference in manifestation of erythema in patients with darker skin (eTable 2).

Comment

The results of this study demonstrated that skin of color is underrepresented in the preclinical dermatology curriculum at these 3 institutions. Although only 16% of all included clinical photographs were of skin of color, individuals with skin of color will soon represent more than half of the total US population within the next 2 decades.¹ To increase representation of skin of color patients, teaching faculty should consciously and deliberately include more photographs of skin of color patients for a wider variety of common conditions, including atopic dermatitis and psoriasis, in addition to those that tend to disparately affect skin of color patients, such as pseudofolliculitis barbae or melasma. Furthermore, they also can incorporate more detailed discussions about important differences seen in skin of color patients.

More Skin of Color Photographs in Psoriasis Lectures—At institution 3, there were no skin of color patients included in the psoriasis lecture, even though there is considerable data in the literature indicating notable differences in the clinical presentation, quality-of-life impact, and treatment of psoriasis in skin of color patients.^11,22 There are multiple nuances in psoriasis manifestation in patients with skin of color, including less-conspicuous erythema in darker skin, higher degrees of dyspigmentation, and greater body surface area involvement. For Black patients with scalp psoriasis, the impact of hair texture, styling practices, and washing frequency are additional considerations that may impact disease severity and selection of topical therapy.¹¹ The lack of inclusion of any skin of color patients in the psoriasis lecture at one institution further underscores the pressing need to prioritize communities of color in medical education.

More Skin of Color Photographs in Cutaneous Malignancy Lectures—Similarly, while a lecturer at institution 2 noted that acral lentiginous melanoma accounts for a considerable proportion of melanoma among skin of color patients,²³ there was no mention of how melanoma generally is substantially more deadly in this population, potentially due to decreased awareness and inconsistent screening.²⁴ Furthermore, at institutions 1 and 3, there were no photographs or discussion of skin of color patients during the cutaneous malignancy lectures. Evidence shows that more emphasis is needed for melanoma screening and awareness in skin of color populations to improve survival outcomes,²⁴ and this begins with educating not only future dermatologists but all future physicians as well. The failure to include photographs of skin of color patients in discussions or lectures regarding cutaneous malignancies may serve to further perpetuate the harmful misperception that individuals with skin of color are unaffected by skin cancer.^25,26

Analysis of Skin of Color Photographs in Infectious Disease Lectures—In addition, lectures discussing infectious etiologies were among those with the highest proportion of skin of color photographs. This relatively disproportionate representation of skin of color compared to the other lectures may contribute to the development of harmful stereotypes or the stigmatization of skin of color patients. Although skin of color should continue to be represented in similar lectures, teaching faculty should remain mindful of the potential unintended impact from lectures including relatively disproportionate amounts of skin of color, particularly when other lectures may have sparse to absent representation of skin of color.

More Photographs Available for Education—Overall, our findings may help to inform changes to preclinical dermatology medical education at other institutions to create more inclusive and representative curricula for skin of color patients. The ability of instructors to provide visual representation of various dermatologic conditions may be limited by the photographs available in certain textbooks with few examples of patients with skin of color; however, concerns regarding the lack of skin of color representation in dermatology training is not a novel discussion.¹⁷ Although it is the responsibility of all dermatologists to advocate for the inclusion of skin of color, many dermatologists of color have been leading the way in this movement for decades, publishing several textbooks to document various skin conditions in those with darker skin types and discuss unique considerations for patients with skin of color.^27-29 Images from these textbooks can be utilized by programs to increase representation of skin of color in dermatology training. There also are multiple expanding online dermatologic databases, such as VisualDx, with an increasing focus on skin of color patients, some of which allow users to filter images by degree of skin pigmentation.³⁰ Moreover, instructors also can work to diversify their curricula by highlighting more of the SOCS conditions of importance to skin of color patients, which have since been renamed and highlighted on the Patient Dermatology Education section of the SOCS website.²⁰ These conditions, while not completely comprehensive, provide a useful starting point for medical educators to reevaluate for potential areas of improvement and inclusion.

There are several potential strategies that can be used to better represent skin of color in dermatologic preclinical medical education, including increasing awareness, especially among dermatology teaching faculty, of existing disparities in the representation of skin of color in the preclinical curricula. Additionally, all dermatology teaching materials could be reviewed at the department level prior to being disseminated to medical students to assess for instances in which skin of color could be prioritized for discussion or varying disease presentations in skin of color could be demonstrated. Finally, teaching faculty may consider photographing more clinical images of their skin of color patients to further develop a catalog of diverse images that can be used to teach students.

Study Limitations—Our study was unable to account for verbal discussion of skin of color not otherwise denoted or captured in lecture slides. Additional limitations include the utilization of Fitzpatrick skin types to describe and differentiate varying skin tones, as the Fitzpatrick scale originally was developed as a method to describe an individual’s response to UV exposure.¹⁹ The inability to further delineate the representation of darker skin types, such as those that may be classified as Fitzpatrick skin types V or VI,¹⁹ compared to those with lighter skin of color also was a limiting factor. This study was unable to assess for discussion of other common conditions affecting skin of color patients that were not listed as one of the priority conditions by SOCS. Photographs that were designated as indeterminate were difficult to elucidate as skin of color; however, it is possible that instructors may have verbally described these images as skin of color during lectures. Nonetheless, it may be beneficial for learners if teaching faculty were to clearly label instances where skin of color patients are shown or when notable differences are present.

 

 

Conclusion

Future studies would benefit from the inclusion of audio data from lectures, syllabi, and small group teaching materials from preclinical courses to more accurately assess representation of skin of color in dermatology training. Additionally, future studies also may expand to include images from lectures of overlapping clinical specialties, particularly infectious disease and rheumatology, to provide a broader assessment of skin of color exposure. Furthermore, repeat assessment may be beneficial to assess the longitudinal effectiveness of curricular changes at the institutions included in this study, comparing older lectures to more recent, updated lectures. This study also may be replicated at other medical schools to allow for wider comparison of curricula.

Acknowledgment—The authors wish to thank the institutions that offered and agreed to participate in this study with the hopes of improving medical education.

A ccording to the US Census Bureau, more than half of all Americans are projected to belong to a minority group, defined as any group other than non-Hispanic White alone, by 2044. ¹ Consequently, the United States rapidly is becoming a country in which the majority of citizens will have skin of color. Individuals with skin of color are of diverse ethnic backgrounds and include people of African, Latin American, Native American, Pacific Islander, and Asian descent, as well as interethnic backgrounds. ² Throughout the country, dermatologists along with primary care practitioners may be confronted with certain cutaneous conditions that have varying disease presentations or processes in patients with skin of color. It also is important to note that racial categories are socially rather than biologically constructed, and the term skin of color includes a wide variety of diverse skin types. Nevertheless, the current literature thoroughly supports unique pathophysiologic differences in skin of color as well as variations in disease manifestation compared to White patients. ^3-5 For example, the increased lability of melanosomes in skin of color patients, which increases their risk for postinflammatory hyperpigmentation, has been well documented. ^5-7 There are various dermatologic conditions that also occur with higher frequency and manifest uniquely in people with darker, more pigmented skin, ^7-9 and dermatologists, along with primary care physicians, should feel prepared to recognize and address them.

Extensive evidence also indicates that there are unique aspects to consider while managing certain skin diseases in patients with skin of color.^8,10,11 Consequently, as noted on the Skin of Color Society (SOCS) website, “[a]n increase in the body of dermatological literature concerning skin of color as well as the advancement of both basic science and clinical investigational research is necessary to meet the needs of the expanding skin of color population.”² In the meantime, current knowledge regarding cutaneous conditions that diversely or disproportionately affect skin of color should be actively disseminated to physicians in training. Although patients with skin of color should always have access to comprehensive care and knowledgeable practitioners, the current changes in national and regional demographics further underscore the need for a more thorough understanding of skin of color with regard to disease pathogenesis, diagnosis, and treatment.

Several studies have found that medical students in the United States are minimally exposed to dermatology in general compared to other clinical specialties,^12-14 which can easily lead to the underrecognition of disorders that may uniquely or disproportionately affect individuals with pigmented skin. Recent data showed that medical schools typically required fewer than 10 hours of dermatology instruction,¹² and on average, dermatologic training made up less than 1% of a medical student’s undergraduate medical education.^13,15,16 Consequently, less than 40% of primary care residents felt that their medical school curriculum adequately prepared them to manage common skin conditions.¹⁴ Although not all physicians should be expected to fully grasp the complexities of skin of color and its diagnostic and therapeutic implications, both practicing and training dermatologists have acknowledged a lack of exposure to skin of color. In one study, approximately 47% of dermatologists and dermatology residents reported that their medical training (medical school and/or residency) was inadequate in training them on skin conditions in Black patients. Furthermore, many who felt their training was lacking in skin of color identified the need for greater exposure to Black patients and training materials.¹⁵ The absence of comprehensive medical education regarding skin of color ultimately can be a disadvantage for both practitioners and patients, resulting in poorer outcomes. Furthermore, underrepresentation of skin of color may persist beyond undergraduate and graduate medical education. There also is evidence to suggest that noninclusion of skin of color pervades foundational dermatologic educational resources, including commonly used textbooks as well as continuing medical education disseminated at national conferences and meetings.¹⁷ Taken together, these findings highlight the need for more diverse and representative exposure to skin of color throughout medical training, which begins with a diverse inclusive undergraduate medical education in dermatology.

The objective of this study was to determine if the preclinical dermatology curriculum at 3 US medical schools provided adequate representation of skin of color patients in their didactic presentation slides.

Methods

Participants—Three US medical schools, a blend of private and public medical schools located across different geographic boundaries, agreed to participate in the study. All 3 institutions were current members of the American Medical Association (AMA) Accelerating Change in Medical Education consortium, whose primary goal is to create the medical school of the future and transform physician training.¹⁸ All 32 member institutions of the AMA consortium were contacted to request their participation in the study. As part of the consortium, these institutions have vowed to collectively work to develop and share the best models for educational advancement to improve care for patients, populations, and communities¹⁸ and would expectedly provide a more racially and ethnically inclusive curriculum than an institution not accountable to a group dedicated to identifying the best ways to deliver care for increasingly diverse communities.

Data Collection—Lectures were included if they were presented during dermatology preclinical courses in the 2015 to 2016 academic year. An uninvolved third party removed the names and identities of instructors to preserve anonymity. Two independent coders from different institutions extracted the data—lecture title, total number of clinical and histologic images, and number of skin of color images—from each of the anonymized lectures using a standardized coding form. We documented differences in skin of color noted in lectures and the disease context for the discussed differences, such as variations in clinical presentation, disease process, epidemiology/risk, and treatment between different skin phenotypes or ethnic groups. Photographs in which the coders were unable to differentiate whether the patient had skin of color were designated as indeterminate or unclear. Photographs appearing to represent Fitzpatrick skin types IV, V, and VI¹⁹ were categorically designated as skin of color, and those appearing to represent Fitzpatrick skin types I and II were described as not skin of color; however, images appearing to represent Fitzpatrick skin type III often were classified as not skin of color or indeterminate and occasionally skin of color. The Figure shows examples of images classified as skin of color, indeterminate, and not skin of color. Photographs often were classified as indeterminate due to poor lighting, close-up view photographs, or highlighted pathology obscuring the surrounding skin. We excluded duplicate photographs and histologic images from the analyses.

We also reviewed 19 conditions previously highlighted by the SOCS as areas of importance to skin of color patients.²⁰ The coders tracked how many of these conditions were noted in each lecture. Duplicate discussion of these conditions was not included in the analyses. Any discrepancies between coders were resolved through additional slide review and discussion. The final coded data with the agreed upon changes were used for statistical analyses. Recent national demographic data from the US Census Bureau in 2019 describe approximately 39.9% of the population as belonging to racial/ethnic groups other than non-Hispanic/Latinx White.²¹ Consequently, the standard for adequate representation for skin of color photographs was set at 35% for the purpose of this study.

 

 

Results

Across all 3 institutions included in the study, the proportion of the total number of clinical photographs showing skin of color was 16% (290/1812). Eight percent of the total photographs (145/1812) were noted to be indeterminate (Table). For institution 1, 23.6% of photographs (155/658) showed skin of color, and 12.6% (83/658) were indeterminate. For institution 2, 13.1% (76/578) showed skin of color and 7.8% (45/578) were indeterminate. For institution 3, 10.2% (59/576) showed skin of color and 3% (17/576) were indeterminate.

Institutions 1, 2, and 3 had 18, 8, and 17 total dermatology lectures, respectively. Of the 19 conditions designated as areas of importance to skin of color patients by the SOCS, 16 (84.2%) were discussed by institution 1, 11 (57.9%) by institution 2, and 9 (47.4%) by institution 3 (eTable 1). Institution 3 did not include photographs of skin of color patients in its acne, psoriasis, or cutaneous malignancy lectures. Institution 1 also did not include any skin of color patients in its malignancy lecture. Lectures that focused on pigmentary disorders, atopic dermatitis, infectious conditions, and benign cutaneous neoplasms were more likely to display photographs of skin of color patients; for example, lectures that discussed infectious conditions, such as superficial mycoses, herpes viruses, human papillomavirus, syphilis, and atypical mycobacterial infections, were consistently among those with higher proportions of photographs of skin of color patients.

Throughout the entire preclinical dermatology course at all 3 institutions, of 2945 lecture slides, only 24 (0.8%) unique differences were noted between skin color and non–skin of color patients, with 10 total differences noted by institution 1, 6 by institution 2, and 8 by institution 3 (Table). The majority of these differences (19/24) were related to epidemiologic differences in prevalence among varying racial/ethnic groups, with only 5 instances highlighting differences in clinical presentation. There was only a single instance that elaborated on the underlying pathophysiologic mechanisms of the discussed difference. Of all 24 unique differences discussed, 8 were related to skin cancer, 3 were related to dermatitis, and 2 were related to the difference in manifestation of erythema in patients with darker skin (eTable 2).

Comment

The results of this study demonstrated that skin of color is underrepresented in the preclinical dermatology curriculum at these 3 institutions. Although only 16% of all included clinical photographs were of skin of color, individuals with skin of color will soon represent more than half of the total US population within the next 2 decades.¹ To increase representation of skin of color patients, teaching faculty should consciously and deliberately include more photographs of skin of color patients for a wider variety of common conditions, including atopic dermatitis and psoriasis, in addition to those that tend to disparately affect skin of color patients, such as pseudofolliculitis barbae or melasma. Furthermore, they also can incorporate more detailed discussions about important differences seen in skin of color patients.

More Skin of Color Photographs in Psoriasis Lectures—At institution 3, there were no skin of color patients included in the psoriasis lecture, even though there is considerable data in the literature indicating notable differences in the clinical presentation, quality-of-life impact, and treatment of psoriasis in skin of color patients.^11,22 There are multiple nuances in psoriasis manifestation in patients with skin of color, including less-conspicuous erythema in darker skin, higher degrees of dyspigmentation, and greater body surface area involvement. For Black patients with scalp psoriasis, the impact of hair texture, styling practices, and washing frequency are additional considerations that may impact disease severity and selection of topical therapy.¹¹ The lack of inclusion of any skin of color patients in the psoriasis lecture at one institution further underscores the pressing need to prioritize communities of color in medical education.

More Skin of Color Photographs in Cutaneous Malignancy Lectures—Similarly, while a lecturer at institution 2 noted that acral lentiginous melanoma accounts for a considerable proportion of melanoma among skin of color patients,²³ there was no mention of how melanoma generally is substantially more deadly in this population, potentially due to decreased awareness and inconsistent screening.²⁴ Furthermore, at institutions 1 and 3, there were no photographs or discussion of skin of color patients during the cutaneous malignancy lectures. Evidence shows that more emphasis is needed for melanoma screening and awareness in skin of color populations to improve survival outcomes,²⁴ and this begins with educating not only future dermatologists but all future physicians as well. The failure to include photographs of skin of color patients in discussions or lectures regarding cutaneous malignancies may serve to further perpetuate the harmful misperception that individuals with skin of color are unaffected by skin cancer.^25,26

Analysis of Skin of Color Photographs in Infectious Disease Lectures—In addition, lectures discussing infectious etiologies were among those with the highest proportion of skin of color photographs. This relatively disproportionate representation of skin of color compared to the other lectures may contribute to the development of harmful stereotypes or the stigmatization of skin of color patients. Although skin of color should continue to be represented in similar lectures, teaching faculty should remain mindful of the potential unintended impact from lectures including relatively disproportionate amounts of skin of color, particularly when other lectures may have sparse to absent representation of skin of color.

More Photographs Available for Education—Overall, our findings may help to inform changes to preclinical dermatology medical education at other institutions to create more inclusive and representative curricula for skin of color patients. The ability of instructors to provide visual representation of various dermatologic conditions may be limited by the photographs available in certain textbooks with few examples of patients with skin of color; however, concerns regarding the lack of skin of color representation in dermatology training is not a novel discussion.¹⁷ Although it is the responsibility of all dermatologists to advocate for the inclusion of skin of color, many dermatologists of color have been leading the way in this movement for decades, publishing several textbooks to document various skin conditions in those with darker skin types and discuss unique considerations for patients with skin of color.^27-29 Images from these textbooks can be utilized by programs to increase representation of skin of color in dermatology training. There also are multiple expanding online dermatologic databases, such as VisualDx, with an increasing focus on skin of color patients, some of which allow users to filter images by degree of skin pigmentation.³⁰ Moreover, instructors also can work to diversify their curricula by highlighting more of the SOCS conditions of importance to skin of color patients, which have since been renamed and highlighted on the Patient Dermatology Education section of the SOCS website.²⁰ These conditions, while not completely comprehensive, provide a useful starting point for medical educators to reevaluate for potential areas of improvement and inclusion.

There are several potential strategies that can be used to better represent skin of color in dermatologic preclinical medical education, including increasing awareness, especially among dermatology teaching faculty, of existing disparities in the representation of skin of color in the preclinical curricula. Additionally, all dermatology teaching materials could be reviewed at the department level prior to being disseminated to medical students to assess for instances in which skin of color could be prioritized for discussion or varying disease presentations in skin of color could be demonstrated. Finally, teaching faculty may consider photographing more clinical images of their skin of color patients to further develop a catalog of diverse images that can be used to teach students.

Study Limitations—Our study was unable to account for verbal discussion of skin of color not otherwise denoted or captured in lecture slides. Additional limitations include the utilization of Fitzpatrick skin types to describe and differentiate varying skin tones, as the Fitzpatrick scale originally was developed as a method to describe an individual’s response to UV exposure.¹⁹ The inability to further delineate the representation of darker skin types, such as those that may be classified as Fitzpatrick skin types V or VI,¹⁹ compared to those with lighter skin of color also was a limiting factor. This study was unable to assess for discussion of other common conditions affecting skin of color patients that were not listed as one of the priority conditions by SOCS. Photographs that were designated as indeterminate were difficult to elucidate as skin of color; however, it is possible that instructors may have verbally described these images as skin of color during lectures. Nonetheless, it may be beneficial for learners if teaching faculty were to clearly label instances where skin of color patients are shown or when notable differences are present.

 

 

Conclusion

Future studies would benefit from the inclusion of audio data from lectures, syllabi, and small group teaching materials from preclinical courses to more accurately assess representation of skin of color in dermatology training. Additionally, future studies also may expand to include images from lectures of overlapping clinical specialties, particularly infectious disease and rheumatology, to provide a broader assessment of skin of color exposure. Furthermore, repeat assessment may be beneficial to assess the longitudinal effectiveness of curricular changes at the institutions included in this study, comparing older lectures to more recent, updated lectures. This study also may be replicated at other medical schools to allow for wider comparison of curricula.

Acknowledgment—The authors wish to thank the institutions that offered and agreed to participate in this study with the hopes of improving medical education.

A ccording to the US Census Bureau, more than half of all Americans are projected to belong to a minority group, defined as any group other than non-Hispanic White alone, by 2044. ¹ Consequently, the United States rapidly is becoming a country in which the majority of citizens will have skin of color. Individuals with skin of color are of diverse ethnic backgrounds and include people of African, Latin American, Native American, Pacific Islander, and Asian descent, as well as interethnic backgrounds. ² Throughout the country, dermatologists along with primary care practitioners may be confronted with certain cutaneous conditions that have varying disease presentations or processes in patients with skin of color. It also is important to note that racial categories are socially rather than biologically constructed, and the term skin of color includes a wide variety of diverse skin types. Nevertheless, the current literature thoroughly supports unique pathophysiologic differences in skin of color as well as variations in disease manifestation compared to White patients. ^3-5 For example, the increased lability of melanosomes in skin of color patients, which increases their risk for postinflammatory hyperpigmentation, has been well documented. ^5-7 There are various dermatologic conditions that also occur with higher frequency and manifest uniquely in people with darker, more pigmented skin, ^7-9 and dermatologists, along with primary care physicians, should feel prepared to recognize and address them.

Extensive evidence also indicates that there are unique aspects to consider while managing certain skin diseases in patients with skin of color.^8,10,11 Consequently, as noted on the Skin of Color Society (SOCS) website, “[a]n increase in the body of dermatological literature concerning skin of color as well as the advancement of both basic science and clinical investigational research is necessary to meet the needs of the expanding skin of color population.”² In the meantime, current knowledge regarding cutaneous conditions that diversely or disproportionately affect skin of color should be actively disseminated to physicians in training. Although patients with skin of color should always have access to comprehensive care and knowledgeable practitioners, the current changes in national and regional demographics further underscore the need for a more thorough understanding of skin of color with regard to disease pathogenesis, diagnosis, and treatment.

Several studies have found that medical students in the United States are minimally exposed to dermatology in general compared to other clinical specialties,^12-14 which can easily lead to the underrecognition of disorders that may uniquely or disproportionately affect individuals with pigmented skin. Recent data showed that medical schools typically required fewer than 10 hours of dermatology instruction,¹² and on average, dermatologic training made up less than 1% of a medical student’s undergraduate medical education.^13,15,16 Consequently, less than 40% of primary care residents felt that their medical school curriculum adequately prepared them to manage common skin conditions.¹⁴ Although not all physicians should be expected to fully grasp the complexities of skin of color and its diagnostic and therapeutic implications, both practicing and training dermatologists have acknowledged a lack of exposure to skin of color. In one study, approximately 47% of dermatologists and dermatology residents reported that their medical training (medical school and/or residency) was inadequate in training them on skin conditions in Black patients. Furthermore, many who felt their training was lacking in skin of color identified the need for greater exposure to Black patients and training materials.¹⁵ The absence of comprehensive medical education regarding skin of color ultimately can be a disadvantage for both practitioners and patients, resulting in poorer outcomes. Furthermore, underrepresentation of skin of color may persist beyond undergraduate and graduate medical education. There also is evidence to suggest that noninclusion of skin of color pervades foundational dermatologic educational resources, including commonly used textbooks as well as continuing medical education disseminated at national conferences and meetings.¹⁷ Taken together, these findings highlight the need for more diverse and representative exposure to skin of color throughout medical training, which begins with a diverse inclusive undergraduate medical education in dermatology.

The objective of this study was to determine if the preclinical dermatology curriculum at 3 US medical schools provided adequate representation of skin of color patients in their didactic presentation slides.

Methods

Participants—Three US medical schools, a blend of private and public medical schools located across different geographic boundaries, agreed to participate in the study. All 3 institutions were current members of the American Medical Association (AMA) Accelerating Change in Medical Education consortium, whose primary goal is to create the medical school of the future and transform physician training.¹⁸ All 32 member institutions of the AMA consortium were contacted to request their participation in the study. As part of the consortium, these institutions have vowed to collectively work to develop and share the best models for educational advancement to improve care for patients, populations, and communities¹⁸ and would expectedly provide a more racially and ethnically inclusive curriculum than an institution not accountable to a group dedicated to identifying the best ways to deliver care for increasingly diverse communities.

Data Collection—Lectures were included if they were presented during dermatology preclinical courses in the 2015 to 2016 academic year. An uninvolved third party removed the names and identities of instructors to preserve anonymity. Two independent coders from different institutions extracted the data—lecture title, total number of clinical and histologic images, and number of skin of color images—from each of the anonymized lectures using a standardized coding form. We documented differences in skin of color noted in lectures and the disease context for the discussed differences, such as variations in clinical presentation, disease process, epidemiology/risk, and treatment between different skin phenotypes or ethnic groups. Photographs in which the coders were unable to differentiate whether the patient had skin of color were designated as indeterminate or unclear. Photographs appearing to represent Fitzpatrick skin types IV, V, and VI¹⁹ were categorically designated as skin of color, and those appearing to represent Fitzpatrick skin types I and II were described as not skin of color; however, images appearing to represent Fitzpatrick skin type III often were classified as not skin of color or indeterminate and occasionally skin of color. The Figure shows examples of images classified as skin of color, indeterminate, and not skin of color. Photographs often were classified as indeterminate due to poor lighting, close-up view photographs, or highlighted pathology obscuring the surrounding skin. We excluded duplicate photographs and histologic images from the analyses.

We also reviewed 19 conditions previously highlighted by the SOCS as areas of importance to skin of color patients.²⁰ The coders tracked how many of these conditions were noted in each lecture. Duplicate discussion of these conditions was not included in the analyses. Any discrepancies between coders were resolved through additional slide review and discussion. The final coded data with the agreed upon changes were used for statistical analyses. Recent national demographic data from the US Census Bureau in 2019 describe approximately 39.9% of the population as belonging to racial/ethnic groups other than non-Hispanic/Latinx White.²¹ Consequently, the standard for adequate representation for skin of color photographs was set at 35% for the purpose of this study.

 

 

Results

Across all 3 institutions included in the study, the proportion of the total number of clinical photographs showing skin of color was 16% (290/1812). Eight percent of the total photographs (145/1812) were noted to be indeterminate (Table). For institution 1, 23.6% of photographs (155/658) showed skin of color, and 12.6% (83/658) were indeterminate. For institution 2, 13.1% (76/578) showed skin of color and 7.8% (45/578) were indeterminate. For institution 3, 10.2% (59/576) showed skin of color and 3% (17/576) were indeterminate.

Institutions 1, 2, and 3 had 18, 8, and 17 total dermatology lectures, respectively. Of the 19 conditions designated as areas of importance to skin of color patients by the SOCS, 16 (84.2%) were discussed by institution 1, 11 (57.9%) by institution 2, and 9 (47.4%) by institution 3 (eTable 1). Institution 3 did not include photographs of skin of color patients in its acne, psoriasis, or cutaneous malignancy lectures. Institution 1 also did not include any skin of color patients in its malignancy lecture. Lectures that focused on pigmentary disorders, atopic dermatitis, infectious conditions, and benign cutaneous neoplasms were more likely to display photographs of skin of color patients; for example, lectures that discussed infectious conditions, such as superficial mycoses, herpes viruses, human papillomavirus, syphilis, and atypical mycobacterial infections, were consistently among those with higher proportions of photographs of skin of color patients.

Throughout the entire preclinical dermatology course at all 3 institutions, of 2945 lecture slides, only 24 (0.8%) unique differences were noted between skin color and non–skin of color patients, with 10 total differences noted by institution 1, 6 by institution 2, and 8 by institution 3 (Table). The majority of these differences (19/24) were related to epidemiologic differences in prevalence among varying racial/ethnic groups, with only 5 instances highlighting differences in clinical presentation. There was only a single instance that elaborated on the underlying pathophysiologic mechanisms of the discussed difference. Of all 24 unique differences discussed, 8 were related to skin cancer, 3 were related to dermatitis, and 2 were related to the difference in manifestation of erythema in patients with darker skin (eTable 2).

Comment

The results of this study demonstrated that skin of color is underrepresented in the preclinical dermatology curriculum at these 3 institutions. Although only 16% of all included clinical photographs were of skin of color, individuals with skin of color will soon represent more than half of the total US population within the next 2 decades.¹ To increase representation of skin of color patients, teaching faculty should consciously and deliberately include more photographs of skin of color patients for a wider variety of common conditions, including atopic dermatitis and psoriasis, in addition to those that tend to disparately affect skin of color patients, such as pseudofolliculitis barbae or melasma. Furthermore, they also can incorporate more detailed discussions about important differences seen in skin of color patients.

More Skin of Color Photographs in Psoriasis Lectures—At institution 3, there were no skin of color patients included in the psoriasis lecture, even though there is considerable data in the literature indicating notable differences in the clinical presentation, quality-of-life impact, and treatment of psoriasis in skin of color patients.^11,22 There are multiple nuances in psoriasis manifestation in patients with skin of color, including less-conspicuous erythema in darker skin, higher degrees of dyspigmentation, and greater body surface area involvement. For Black patients with scalp psoriasis, the impact of hair texture, styling practices, and washing frequency are additional considerations that may impact disease severity and selection of topical therapy.¹¹ The lack of inclusion of any skin of color patients in the psoriasis lecture at one institution further underscores the pressing need to prioritize communities of color in medical education.

More Skin of Color Photographs in Cutaneous Malignancy Lectures—Similarly, while a lecturer at institution 2 noted that acral lentiginous melanoma accounts for a considerable proportion of melanoma among skin of color patients,²³ there was no mention of how melanoma generally is substantially more deadly in this population, potentially due to decreased awareness and inconsistent screening.²⁴ Furthermore, at institutions 1 and 3, there were no photographs or discussion of skin of color patients during the cutaneous malignancy lectures. Evidence shows that more emphasis is needed for melanoma screening and awareness in skin of color populations to improve survival outcomes,²⁴ and this begins with educating not only future dermatologists but all future physicians as well. The failure to include photographs of skin of color patients in discussions or lectures regarding cutaneous malignancies may serve to further perpetuate the harmful misperception that individuals with skin of color are unaffected by skin cancer.^25,26

Analysis of Skin of Color Photographs in Infectious Disease Lectures—In addition, lectures discussing infectious etiologies were among those with the highest proportion of skin of color photographs. This relatively disproportionate representation of skin of color compared to the other lectures may contribute to the development of harmful stereotypes or the stigmatization of skin of color patients. Although skin of color should continue to be represented in similar lectures, teaching faculty should remain mindful of the potential unintended impact from lectures including relatively disproportionate amounts of skin of color, particularly when other lectures may have sparse to absent representation of skin of color.

More Photographs Available for Education—Overall, our findings may help to inform changes to preclinical dermatology medical education at other institutions to create more inclusive and representative curricula for skin of color patients. The ability of instructors to provide visual representation of various dermatologic conditions may be limited by the photographs available in certain textbooks with few examples of patients with skin of color; however, concerns regarding the lack of skin of color representation in dermatology training is not a novel discussion.¹⁷ Although it is the responsibility of all dermatologists to advocate for the inclusion of skin of color, many dermatologists of color have been leading the way in this movement for decades, publishing several textbooks to document various skin conditions in those with darker skin types and discuss unique considerations for patients with skin of color.^27-29 Images from these textbooks can be utilized by programs to increase representation of skin of color in dermatology training. There also are multiple expanding online dermatologic databases, such as VisualDx, with an increasing focus on skin of color patients, some of which allow users to filter images by degree of skin pigmentation.³⁰ Moreover, instructors also can work to diversify their curricula by highlighting more of the SOCS conditions of importance to skin of color patients, which have since been renamed and highlighted on the Patient Dermatology Education section of the SOCS website.²⁰ These conditions, while not completely comprehensive, provide a useful starting point for medical educators to reevaluate for potential areas of improvement and inclusion.

There are several potential strategies that can be used to better represent skin of color in dermatologic preclinical medical education, including increasing awareness, especially among dermatology teaching faculty, of existing disparities in the representation of skin of color in the preclinical curricula. Additionally, all dermatology teaching materials could be reviewed at the department level prior to being disseminated to medical students to assess for instances in which skin of color could be prioritized for discussion or varying disease presentations in skin of color could be demonstrated. Finally, teaching faculty may consider photographing more clinical images of their skin of color patients to further develop a catalog of diverse images that can be used to teach students.

Study Limitations—Our study was unable to account for verbal discussion of skin of color not otherwise denoted or captured in lecture slides. Additional limitations include the utilization of Fitzpatrick skin types to describe and differentiate varying skin tones, as the Fitzpatrick scale originally was developed as a method to describe an individual’s response to UV exposure.¹⁹ The inability to further delineate the representation of darker skin types, such as those that may be classified as Fitzpatrick skin types V or VI,¹⁹ compared to those with lighter skin of color also was a limiting factor. This study was unable to assess for discussion of other common conditions affecting skin of color patients that were not listed as one of the priority conditions by SOCS. Photographs that were designated as indeterminate were difficult to elucidate as skin of color; however, it is possible that instructors may have verbally described these images as skin of color during lectures. Nonetheless, it may be beneficial for learners if teaching faculty were to clearly label instances where skin of color patients are shown or when notable differences are present.

 

 

Conclusion

Future studies would benefit from the inclusion of audio data from lectures, syllabi, and small group teaching materials from preclinical courses to more accurately assess representation of skin of color in dermatology training. Additionally, future studies also may expand to include images from lectures of overlapping clinical specialties, particularly infectious disease and rheumatology, to provide a broader assessment of skin of color exposure. Furthermore, repeat assessment may be beneficial to assess the longitudinal effectiveness of curricular changes at the institutions included in this study, comparing older lectures to more recent, updated lectures. This study also may be replicated at other medical schools to allow for wider comparison of curricula.

Acknowledgment—The authors wish to thank the institutions that offered and agreed to participate in this study with the hopes of improving medical education.

Many patients with cancer, as well as doctors in fields other than oncology, are unaware of just how much progress has been made in recent years in the treatment of cancer, particularly with immunotherapy.

This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.

The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.

When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.

Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.

“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.

After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”

Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.

Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.

He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.

“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.

That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.

For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
 

Findings from the patient survey

It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.

“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients

The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.

The survey asked them about how immunotherapy works, what it costs, and its side effects.

Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”

Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.

“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.

A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.

“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.

Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
 

Results of the doctor survey

The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.

Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).

Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.

Both groups of doctors had a hard time estimating the survival of common cancers.

Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.

However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.

“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.

A version of this article first appeared on Medscape.com.

Many patients with cancer, as well as doctors in fields other than oncology, are unaware of just how much progress has been made in recent years in the treatment of cancer, particularly with immunotherapy.

This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.

The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.

When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.

Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.

“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.

After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”

Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.

Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.

He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.

“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.

That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.

For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
 

Findings from the patient survey

It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.

“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients

The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.

The survey asked them about how immunotherapy works, what it costs, and its side effects.

Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”

Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.

“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.

A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.

“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.

Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
 

Results of the doctor survey

The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.

Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).

Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.

Both groups of doctors had a hard time estimating the survival of common cancers.

Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.

However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.

“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.

A version of this article first appeared on Medscape.com.

Many patients with cancer, as well as doctors in fields other than oncology, are unaware of just how much progress has been made in recent years in the treatment of cancer, particularly with immunotherapy.

This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.

The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.

When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.

Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.

“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.

After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”

Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.

Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.

He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.

“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.

That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.

For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
 

Findings from the patient survey

It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.

“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients

The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.

The survey asked them about how immunotherapy works, what it costs, and its side effects.

Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”

Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.

“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.

A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.

“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.

Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
 

Results of the doctor survey

The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.

Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).

Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.

Both groups of doctors had a hard time estimating the survival of common cancers.

Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.

However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.

“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.

A version of this article first appeared on Medscape.com.

The proportion of patients who obtained an opioid prescription for hydrocodone after Mohs micrographic surgery fell by 21.7% between 2011 and 2020, while the use of tramadol increased by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.

The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.

“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”

As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.

“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”

The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.

The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.

“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.

“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”

State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.

“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”

Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”

Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.

“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”

The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.

dbrunk@mdedge.com

The proportion of patients who obtained an opioid prescription for hydrocodone after Mohs micrographic surgery fell by 21.7% between 2011 and 2020, while the use of tramadol increased by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.

The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.

“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”

As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.

“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”

The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.

The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.

“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.

“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”

State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.

“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”

Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”

Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.

“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”

The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.

dbrunk@mdedge.com

The proportion of patients who obtained an opioid prescription for hydrocodone after Mohs micrographic surgery fell by 21.7% between 2011 and 2020, while the use of tramadol increased by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.

The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.

“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”

As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.

“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”

The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.

The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.

“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.

“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”

State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.

“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”

Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”

Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.

“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”

The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.

dbrunk@mdedge.com

Federal efforts to improve the quality, safety, and efficacy of over-the-counter sunscreens took a step forward today with the release of two orders aimed at updating regulatory requirements for most sunscreen products in the United States.

“We see it as a key public health priority and our regulatory obligation to make sure that marketed sunscreen products offer protection from the sun’s effects and that they deliver on those promises to consumers,” Theresa Michele, MD, director of the office of nonprescription drugs in the FDA’s Center for Drug Evaluation and Research, said during a media briefing.

When the Coronavirus Aid, Relief, and Economic Security (CARES) Act was passed in 2020, the FDA was in the middle of amending a sunscreen monograph through the previous rule-making process, and the agency had issued a proposed rule for sunscreens in February of 2019. The CARES Act provided the FDA with new authority related to OTC drugs including sunscreens.

It also established a deemed final order for sunscreens, which set the current requirements for OTC sunscreen products marketed without an application. The deemed final order, released on Sept. 24, “essentially preserves the pre-CARES Act status quo marketing conditions for these sunscreens,” Dr. Michele explained. “Before the CARES Act was passed, sunscreens were marketed according to nearly identical terms that were described in an FDA enforcement discretion policy. For this reason, the agency believes that most sunscreens on the market today are already in compliance with this order.”

The CARES Act also required the FDA to issue a proposed order by Sept. 27 to amend and revise the deemed final order. Dr. Michele described the proposed order, which was released on Sept. 24, as “a vehicle to effectively transition our ongoing consideration of the appropriate requirements for OTC sunscreens marketed without approved applications from the previous rule-making process to this new order process. The provisions in today’s proposed order are therefore substantively the same as those described in the FDA’s 2019 proposed rule on sunscreens. With this proposed order, we’re proposing new requirements to improve the quality, safety, and efficacy of sunscreens that Americans use every day.”

The order proposes to update the generally recognized as safe (GRASE) status for the 16 active ingredients listed in the deemed final order. It also proposes that dosage forms that are GRASE for use as sunscreens include oils, lotions, creams, gels, butters, pastes, ointments, and sticks, and proposes GRASE status for spray sunscreens, subject to testing and labeling requirements.

Adam Friedman, MD, FAAD, professor and chair of dermatology at George Washington University, Washington, emphasized that photoprotection “is important for everyone, regardless of skin tone,” in an interview. “Broad-spectrum sunscreens with an SPF of 15 and higher play an important role in this. This should not be lost amidst the proposed order.”

Changes between the deemed and proposed order that he highlighted include a maximum SPF of 60+ (though up to 80 might be allowed) and that zinc oxide and titanium dioxide are GRASE. “The FDA did not say that nanoparticle formulations of these, which are easier to use, are not GRASE; they are asking for community input,” he said.

Other changes between the deemed and proposed order are that PABA and trolamine salicylate are not GRASE and that broad-spectrum testing will be mandatory. In addition, Dr. Friedman said, “sprays will be considered for GRASE so long as properly tested, labeling should be clearer (and a warning will be applied to those sunscreens not shown to prevent all the bad stuff with UVR [ultraviolet radiation]), and bug spray–sunscreen combos are a no-go.”

The FDA will consider comments on the proposed order submitted during a 45-day public comment period before issuing a revised final order. “As part of this process, we’ll consider all timely comments submitted both in response to the February 2019 proposed rule and to the current proposed order,” Dr. Michele said.

Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies. He is also a speaker for Regeneron, Sanofi Genzyme, Abbvie, LRP, Janssen, Incyte, and Brickell Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, Incyte, Galderma, and Janssen.

dbrunk@mdedge.com

Federal efforts to improve the quality, safety, and efficacy of over-the-counter sunscreens took a step forward today with the release of two orders aimed at updating regulatory requirements for most sunscreen products in the United States.

“We see it as a key public health priority and our regulatory obligation to make sure that marketed sunscreen products offer protection from the sun’s effects and that they deliver on those promises to consumers,” Theresa Michele, MD, director of the office of nonprescription drugs in the FDA’s Center for Drug Evaluation and Research, said during a media briefing.

When the Coronavirus Aid, Relief, and Economic Security (CARES) Act was passed in 2020, the FDA was in the middle of amending a sunscreen monograph through the previous rule-making process, and the agency had issued a proposed rule for sunscreens in February of 2019. The CARES Act provided the FDA with new authority related to OTC drugs including sunscreens.

It also established a deemed final order for sunscreens, which set the current requirements for OTC sunscreen products marketed without an application. The deemed final order, released on Sept. 24, “essentially preserves the pre-CARES Act status quo marketing conditions for these sunscreens,” Dr. Michele explained. “Before the CARES Act was passed, sunscreens were marketed according to nearly identical terms that were described in an FDA enforcement discretion policy. For this reason, the agency believes that most sunscreens on the market today are already in compliance with this order.”

The CARES Act also required the FDA to issue a proposed order by Sept. 27 to amend and revise the deemed final order. Dr. Michele described the proposed order, which was released on Sept. 24, as “a vehicle to effectively transition our ongoing consideration of the appropriate requirements for OTC sunscreens marketed without approved applications from the previous rule-making process to this new order process. The provisions in today’s proposed order are therefore substantively the same as those described in the FDA’s 2019 proposed rule on sunscreens. With this proposed order, we’re proposing new requirements to improve the quality, safety, and efficacy of sunscreens that Americans use every day.”

The order proposes to update the generally recognized as safe (GRASE) status for the 16 active ingredients listed in the deemed final order. It also proposes that dosage forms that are GRASE for use as sunscreens include oils, lotions, creams, gels, butters, pastes, ointments, and sticks, and proposes GRASE status for spray sunscreens, subject to testing and labeling requirements.

Adam Friedman, MD, FAAD, professor and chair of dermatology at George Washington University, Washington, emphasized that photoprotection “is important for everyone, regardless of skin tone,” in an interview. “Broad-spectrum sunscreens with an SPF of 15 and higher play an important role in this. This should not be lost amidst the proposed order.”

Changes between the deemed and proposed order that he highlighted include a maximum SPF of 60+ (though up to 80 might be allowed) and that zinc oxide and titanium dioxide are GRASE. “The FDA did not say that nanoparticle formulations of these, which are easier to use, are not GRASE; they are asking for community input,” he said.

Other changes between the deemed and proposed order are that PABA and trolamine salicylate are not GRASE and that broad-spectrum testing will be mandatory. In addition, Dr. Friedman said, “sprays will be considered for GRASE so long as properly tested, labeling should be clearer (and a warning will be applied to those sunscreens not shown to prevent all the bad stuff with UVR [ultraviolet radiation]), and bug spray–sunscreen combos are a no-go.”

The FDA will consider comments on the proposed order submitted during a 45-day public comment period before issuing a revised final order. “As part of this process, we’ll consider all timely comments submitted both in response to the February 2019 proposed rule and to the current proposed order,” Dr. Michele said.

Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies. He is also a speaker for Regeneron, Sanofi Genzyme, Abbvie, LRP, Janssen, Incyte, and Brickell Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, Incyte, Galderma, and Janssen.

dbrunk@mdedge.com

Federal efforts to improve the quality, safety, and efficacy of over-the-counter sunscreens took a step forward today with the release of two orders aimed at updating regulatory requirements for most sunscreen products in the United States.

“We see it as a key public health priority and our regulatory obligation to make sure that marketed sunscreen products offer protection from the sun’s effects and that they deliver on those promises to consumers,” Theresa Michele, MD, director of the office of nonprescription drugs in the FDA’s Center for Drug Evaluation and Research, said during a media briefing.

When the Coronavirus Aid, Relief, and Economic Security (CARES) Act was passed in 2020, the FDA was in the middle of amending a sunscreen monograph through the previous rule-making process, and the agency had issued a proposed rule for sunscreens in February of 2019. The CARES Act provided the FDA with new authority related to OTC drugs including sunscreens.

It also established a deemed final order for sunscreens, which set the current requirements for OTC sunscreen products marketed without an application. The deemed final order, released on Sept. 24, “essentially preserves the pre-CARES Act status quo marketing conditions for these sunscreens,” Dr. Michele explained. “Before the CARES Act was passed, sunscreens were marketed according to nearly identical terms that were described in an FDA enforcement discretion policy. For this reason, the agency believes that most sunscreens on the market today are already in compliance with this order.”

The CARES Act also required the FDA to issue a proposed order by Sept. 27 to amend and revise the deemed final order. Dr. Michele described the proposed order, which was released on Sept. 24, as “a vehicle to effectively transition our ongoing consideration of the appropriate requirements for OTC sunscreens marketed without approved applications from the previous rule-making process to this new order process. The provisions in today’s proposed order are therefore substantively the same as those described in the FDA’s 2019 proposed rule on sunscreens. With this proposed order, we’re proposing new requirements to improve the quality, safety, and efficacy of sunscreens that Americans use every day.”

The order proposes to update the generally recognized as safe (GRASE) status for the 16 active ingredients listed in the deemed final order. It also proposes that dosage forms that are GRASE for use as sunscreens include oils, lotions, creams, gels, butters, pastes, ointments, and sticks, and proposes GRASE status for spray sunscreens, subject to testing and labeling requirements.

Adam Friedman, MD, FAAD, professor and chair of dermatology at George Washington University, Washington, emphasized that photoprotection “is important for everyone, regardless of skin tone,” in an interview. “Broad-spectrum sunscreens with an SPF of 15 and higher play an important role in this. This should not be lost amidst the proposed order.”

Changes between the deemed and proposed order that he highlighted include a maximum SPF of 60+ (though up to 80 might be allowed) and that zinc oxide and titanium dioxide are GRASE. “The FDA did not say that nanoparticle formulations of these, which are easier to use, are not GRASE; they are asking for community input,” he said.

Other changes between the deemed and proposed order are that PABA and trolamine salicylate are not GRASE and that broad-spectrum testing will be mandatory. In addition, Dr. Friedman said, “sprays will be considered for GRASE so long as properly tested, labeling should be clearer (and a warning will be applied to those sunscreens not shown to prevent all the bad stuff with UVR [ultraviolet radiation]), and bug spray–sunscreen combos are a no-go.”

The FDA will consider comments on the proposed order submitted during a 45-day public comment period before issuing a revised final order. “As part of this process, we’ll consider all timely comments submitted both in response to the February 2019 proposed rule and to the current proposed order,” Dr. Michele said.

Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies. He is also a speaker for Regeneron, Sanofi Genzyme, Abbvie, LRP, Janssen, Incyte, and Brickell Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, Incyte, Galderma, and Janssen.

dbrunk@mdedge.com

Among patients with uveal melanoma treated with tebentafusp, circulating tumor DNA (ctDNA) reduction may be a better surrogate of overall survival than RECIST response, according to Alexander Noor Shoushtari, MD, Memorial Sloan Kettering Cancer Center, New York.

Tebentafusp is the first therapy to demonstrate an overall survival (OS) benefit in uveal melanoma, Dr. Shoushtari noted in a 2021 European Society of Medical Oncology Congress virtual oral presentation Sept. 17 (abstract 17570). He noted further that, in prior research, OS was improved regardless of RECISTv1.1 best response, suggesting that better surrogate efficacy endpoints are needed.

Uveal melanoma is a rare melanoma type with low mutational burden, but frequent liver metastases. Benefit from immune checkpoint inhibitors is poor, and there is no established standard of care once the disease becomes metastatic. “Immune checkpoint inhibitors are not as good for treating this type of melanoma as they are for treating cutaneous disease, and traditionally preferred treatment is within clinical trials,” Dr. Shoushtari said. In frontline trials, 1-year survival has been in the 50% range. Tebentafusp is an investigational, first-in-class bispecific soluble T-cell receptor (TCR) therapeutic. It is designed to target gp100 (a melanoma-associated antigen) through a high-affinity TCR-binding domain and an anti-CD3 T-cell–engaging domain, which redirects T cells to kill gp100 positive melanocytic expressing tumor cells.

Prior research has demonstrated a disconnect between RECIST response classification and tebentafusp OS benefit. In the IMCgp100-202 study among patients treated first-line for metastatic uveal melanoma with tebentafusp or investigator choice, intent-to-treat analysis showed a survival probability benefit for tebentafusp (hazard ratio, 0.51; 95% CI, 0.37-0.71), with a best response of progressive disease population HR of 0.43 (95% CI, 0.27-0.68). While the RECIST response rate was only 9.1%, the HR for progression-free survival was 0.73 (95% CI, 0.58-0.94). “That suggests that RECIST is not a fantastic way to predict who will benefit from this drug,” Dr. Shoushtari stated.

Similarly in the IMCgp100-102 study of tebentafusp monotherapy in second-line metastatic uveal melanoma (n = 127), the RECIST response rate was 5%. Duration of response was 8.7 months and median OS was 16.8 months. Historical second-line OS has been reported at 7.8 months. The 1- and 2-year survival (62%/37%) compared favorably with historical rates (37%/15%), as well. Dr. Shoushtari noted that 92% of patients had detectable ctDNA with mutations in known uveal melanoma oncogenes. He pointed out that baseline ctDNA levels significantly correlated with tumor burden. Also, 70% of evaluable patients had any ctDNA reduction, with 0.5-3.2 log reduction in 99.9%, a 0.5 log reduction in 68% and 3 log reduction (cleared) in 14% of patients. ctDNA reduction, Dr. Shoushtari said, was associated with greater mean tumor shrinkage and with less tumor growth. Importantly, there was a linear correlation between ctDNA reduction and better OS (R2, 0.88, P < .0001).

Among all evaluable patients, comparing those with less than 0.5 log ctDNA reduction with those with at least a 0.5 log reduction showed a hazard ratio of 0.56 (95% CI, 0.32-0.95; P = .03). Among those whose best response was progressive disease, 35% had at least a 0.5 log reduction in ctDNA with an OS hazard ratio of 0.44 (95% CI, 0.2-0.94; P = .027), compared with less than a 0.5 log reduction. Among those whose best response was stable disease, 28% had at least 1 log reduction with a hazard ratio of 0.48 (95% CI 0.16-1.43; P = .16) for OS, compared with those with less than 1 log reduction. Dr. Shoushtari pointed out that “14% of patients cleared ctDNA, including some (n = 12) with best RECIST responses of stable or progressive disease. All patients with ctDNA clearance were alive beyond 1 year; with a hazard ratio, compared to those who had not cleared ctDNA, of 0.14 (95% CI, 0.03-0.57).

Summing up, Dr. Shoushtari said that ctDNA was detectable in more than 90% of second-line tebentafusp-treated patients with metastatic uveal melanoma and correlated with tumor burden. About 70% had ctDNA reduction versus 39% with tumor shrinkage and 5% RECIST response. The linear correlation between the magnitude of ctDNA reduction and improved OS on tebentafusp, was uncoupled from best RECIST response. “For tebentafusp, ctDNA reduction may be a better surrogate of overall survival than RECIST response.”

The ESMO-appointed discussant for the study, Christian Rolfo, MD, PhD, MBA, Icahan School of Medicine at Mount Sinai, New York, examined the tebentafusp study author’s claim that the radiographic assessment of tumors may underestimate the effect of tebentafusp, compared with ctDNA. The strengths of the study include, he said, that it is a drug- and tumor-specific evaluation of the role of ctDNA as a surrogate of response. “Its strength is that it shows an important correlation between ctDNA levels and overall survival, and that response rate is evaluated better with ctDNA.” A question that remains open, Dr. Rolfo added, is whether RECIST criteria are still a good comparator for biologic response.

The study was funded by Immunocore Dr. Shoushtari disclosed numerous pharmaceutical-related financial interests.

This article was updated Sept. 24, 2021.

Among patients with uveal melanoma treated with tebentafusp, circulating tumor DNA (ctDNA) reduction may be a better surrogate of overall survival than RECIST response, according to Alexander Noor Shoushtari, MD, Memorial Sloan Kettering Cancer Center, New York.

Tebentafusp is the first therapy to demonstrate an overall survival (OS) benefit in uveal melanoma, Dr. Shoushtari noted in a 2021 European Society of Medical Oncology Congress virtual oral presentation Sept. 17 (abstract 17570). He noted further that, in prior research, OS was improved regardless of RECISTv1.1 best response, suggesting that better surrogate efficacy endpoints are needed.

Uveal melanoma is a rare melanoma type with low mutational burden, but frequent liver metastases. Benefit from immune checkpoint inhibitors is poor, and there is no established standard of care once the disease becomes metastatic. “Immune checkpoint inhibitors are not as good for treating this type of melanoma as they are for treating cutaneous disease, and traditionally preferred treatment is within clinical trials,” Dr. Shoushtari said. In frontline trials, 1-year survival has been in the 50% range. Tebentafusp is an investigational, first-in-class bispecific soluble T-cell receptor (TCR) therapeutic. It is designed to target gp100 (a melanoma-associated antigen) through a high-affinity TCR-binding domain and an anti-CD3 T-cell–engaging domain, which redirects T cells to kill gp100 positive melanocytic expressing tumor cells.

Prior research has demonstrated a disconnect between RECIST response classification and tebentafusp OS benefit. In the IMCgp100-202 study among patients treated first-line for metastatic uveal melanoma with tebentafusp or investigator choice, intent-to-treat analysis showed a survival probability benefit for tebentafusp (hazard ratio, 0.51; 95% CI, 0.37-0.71), with a best response of progressive disease population HR of 0.43 (95% CI, 0.27-0.68). While the RECIST response rate was only 9.1%, the HR for progression-free survival was 0.73 (95% CI, 0.58-0.94). “That suggests that RECIST is not a fantastic way to predict who will benefit from this drug,” Dr. Shoushtari stated.

Similarly in the IMCgp100-102 study of tebentafusp monotherapy in second-line metastatic uveal melanoma (n = 127), the RECIST response rate was 5%. Duration of response was 8.7 months and median OS was 16.8 months. Historical second-line OS has been reported at 7.8 months. The 1- and 2-year survival (62%/37%) compared favorably with historical rates (37%/15%), as well. Dr. Shoushtari noted that 92% of patients had detectable ctDNA with mutations in known uveal melanoma oncogenes. He pointed out that baseline ctDNA levels significantly correlated with tumor burden. Also, 70% of evaluable patients had any ctDNA reduction, with 0.5-3.2 log reduction in 99.9%, a 0.5 log reduction in 68% and 3 log reduction (cleared) in 14% of patients. ctDNA reduction, Dr. Shoushtari said, was associated with greater mean tumor shrinkage and with less tumor growth. Importantly, there was a linear correlation between ctDNA reduction and better OS (R2, 0.88, P < .0001).

Among all evaluable patients, comparing those with less than 0.5 log ctDNA reduction with those with at least a 0.5 log reduction showed a hazard ratio of 0.56 (95% CI, 0.32-0.95; P = .03). Among those whose best response was progressive disease, 35% had at least a 0.5 log reduction in ctDNA with an OS hazard ratio of 0.44 (95% CI, 0.2-0.94; P = .027), compared with less than a 0.5 log reduction. Among those whose best response was stable disease, 28% had at least 1 log reduction with a hazard ratio of 0.48 (95% CI 0.16-1.43; P = .16) for OS, compared with those with less than 1 log reduction. Dr. Shoushtari pointed out that “14% of patients cleared ctDNA, including some (n = 12) with best RECIST responses of stable or progressive disease. All patients with ctDNA clearance were alive beyond 1 year; with a hazard ratio, compared to those who had not cleared ctDNA, of 0.14 (95% CI, 0.03-0.57).

Summing up, Dr. Shoushtari said that ctDNA was detectable in more than 90% of second-line tebentafusp-treated patients with metastatic uveal melanoma and correlated with tumor burden. About 70% had ctDNA reduction versus 39% with tumor shrinkage and 5% RECIST response. The linear correlation between the magnitude of ctDNA reduction and improved OS on tebentafusp, was uncoupled from best RECIST response. “For tebentafusp, ctDNA reduction may be a better surrogate of overall survival than RECIST response.”

The ESMO-appointed discussant for the study, Christian Rolfo, MD, PhD, MBA, Icahan School of Medicine at Mount Sinai, New York, examined the tebentafusp study author’s claim that the radiographic assessment of tumors may underestimate the effect of tebentafusp, compared with ctDNA. The strengths of the study include, he said, that it is a drug- and tumor-specific evaluation of the role of ctDNA as a surrogate of response. “Its strength is that it shows an important correlation between ctDNA levels and overall survival, and that response rate is evaluated better with ctDNA.” A question that remains open, Dr. Rolfo added, is whether RECIST criteria are still a good comparator for biologic response.

The study was funded by Immunocore Dr. Shoushtari disclosed numerous pharmaceutical-related financial interests.

This article was updated Sept. 24, 2021.

Among patients with uveal melanoma treated with tebentafusp, circulating tumor DNA (ctDNA) reduction may be a better surrogate of overall survival than RECIST response, according to Alexander Noor Shoushtari, MD, Memorial Sloan Kettering Cancer Center, New York.

Tebentafusp is the first therapy to demonstrate an overall survival (OS) benefit in uveal melanoma, Dr. Shoushtari noted in a 2021 European Society of Medical Oncology Congress virtual oral presentation Sept. 17 (abstract 17570). He noted further that, in prior research, OS was improved regardless of RECISTv1.1 best response, suggesting that better surrogate efficacy endpoints are needed.

Uveal melanoma is a rare melanoma type with low mutational burden, but frequent liver metastases. Benefit from immune checkpoint inhibitors is poor, and there is no established standard of care once the disease becomes metastatic. “Immune checkpoint inhibitors are not as good for treating this type of melanoma as they are for treating cutaneous disease, and traditionally preferred treatment is within clinical trials,” Dr. Shoushtari said. In frontline trials, 1-year survival has been in the 50% range. Tebentafusp is an investigational, first-in-class bispecific soluble T-cell receptor (TCR) therapeutic. It is designed to target gp100 (a melanoma-associated antigen) through a high-affinity TCR-binding domain and an anti-CD3 T-cell–engaging domain, which redirects T cells to kill gp100 positive melanocytic expressing tumor cells.

Prior research has demonstrated a disconnect between RECIST response classification and tebentafusp OS benefit. In the IMCgp100-202 study among patients treated first-line for metastatic uveal melanoma with tebentafusp or investigator choice, intent-to-treat analysis showed a survival probability benefit for tebentafusp (hazard ratio, 0.51; 95% CI, 0.37-0.71), with a best response of progressive disease population HR of 0.43 (95% CI, 0.27-0.68). While the RECIST response rate was only 9.1%, the HR for progression-free survival was 0.73 (95% CI, 0.58-0.94). “That suggests that RECIST is not a fantastic way to predict who will benefit from this drug,” Dr. Shoushtari stated.

Similarly in the IMCgp100-102 study of tebentafusp monotherapy in second-line metastatic uveal melanoma (n = 127), the RECIST response rate was 5%. Duration of response was 8.7 months and median OS was 16.8 months. Historical second-line OS has been reported at 7.8 months. The 1- and 2-year survival (62%/37%) compared favorably with historical rates (37%/15%), as well. Dr. Shoushtari noted that 92% of patients had detectable ctDNA with mutations in known uveal melanoma oncogenes. He pointed out that baseline ctDNA levels significantly correlated with tumor burden. Also, 70% of evaluable patients had any ctDNA reduction, with 0.5-3.2 log reduction in 99.9%, a 0.5 log reduction in 68% and 3 log reduction (cleared) in 14% of patients. ctDNA reduction, Dr. Shoushtari said, was associated with greater mean tumor shrinkage and with less tumor growth. Importantly, there was a linear correlation between ctDNA reduction and better OS (R2, 0.88, P < .0001).

Among all evaluable patients, comparing those with less than 0.5 log ctDNA reduction with those with at least a 0.5 log reduction showed a hazard ratio of 0.56 (95% CI, 0.32-0.95; P = .03). Among those whose best response was progressive disease, 35% had at least a 0.5 log reduction in ctDNA with an OS hazard ratio of 0.44 (95% CI, 0.2-0.94; P = .027), compared with less than a 0.5 log reduction. Among those whose best response was stable disease, 28% had at least 1 log reduction with a hazard ratio of 0.48 (95% CI 0.16-1.43; P = .16) for OS, compared with those with less than 1 log reduction. Dr. Shoushtari pointed out that “14% of patients cleared ctDNA, including some (n = 12) with best RECIST responses of stable or progressive disease. All patients with ctDNA clearance were alive beyond 1 year; with a hazard ratio, compared to those who had not cleared ctDNA, of 0.14 (95% CI, 0.03-0.57).

Summing up, Dr. Shoushtari said that ctDNA was detectable in more than 90% of second-line tebentafusp-treated patients with metastatic uveal melanoma and correlated with tumor burden. About 70% had ctDNA reduction versus 39% with tumor shrinkage and 5% RECIST response. The linear correlation between the magnitude of ctDNA reduction and improved OS on tebentafusp, was uncoupled from best RECIST response. “For tebentafusp, ctDNA reduction may be a better surrogate of overall survival than RECIST response.”

The ESMO-appointed discussant for the study, Christian Rolfo, MD, PhD, MBA, Icahan School of Medicine at Mount Sinai, New York, examined the tebentafusp study author’s claim that the radiographic assessment of tumors may underestimate the effect of tebentafusp, compared with ctDNA. The strengths of the study include, he said, that it is a drug- and tumor-specific evaluation of the role of ctDNA as a surrogate of response. “Its strength is that it shows an important correlation between ctDNA levels and overall survival, and that response rate is evaluated better with ctDNA.” A question that remains open, Dr. Rolfo added, is whether RECIST criteria are still a good comparator for biologic response.

The study was funded by Immunocore Dr. Shoushtari disclosed numerous pharmaceutical-related financial interests.

This article was updated Sept. 24, 2021.

A recent survey shows that fewer than half of community oncologists use biomarker testing to guide patient discussions about treatment, which compares with 73% of academic clinicians.

The findings, reported at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, highlight the potential for unequal application of the latest advances in cancer genomics and targeted therapies throughout the health care system, which could worsen existing disparities in underserved populations, according to Leigh Boehmer, PharmD, medical director for the Association of Community Cancer Centers, Rockville, Md.

The survey – a mixed-methods approach for assessing practice patterns, attitudes, barriers, and resource needs related to biomarker testing among clinicians – was developed by the ACCC in partnership with the LUNGevity Foundation and administered to clinicians caring for patients with non–small cell lung cancer who are uninsured or covered by Medicaid.

Of 99 respondents, more than 85% were physicians and 68% worked in a community setting. Only 40% indicated they were very familiar or extremely familiar with 2018 Molecular Testing Guidelines for Lung Cancer from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.

Clinicians were most confident about selecting appropriate tests to use, interpreting test results, and prognosticating based on test results, with 77%, 74%, and 74%, respectively, saying they are very confident or extremely confident in those areas. They were less confident about determining when to order testing and in coordinating care across the multidisciplinary team, with 59% and 64%, respectively, saying they were very confident or extremely confident in those areas, Dr. Boehmer reported at the conference.

The shortcomings with respect to communication across teams were echoed in two focus groups convened to further validate the survey results, he noted.

As for the reasons why clinicians ordered biomarker testing, 88% and 82% of community and academic clinicians, respectively, said they did so to help make targeted treatment decisions.

“Only 48% of community clinicians indicated that they use biomarker testing to guide patient discussions, compared to 73% of academic clinicians,” he said. “That finding was considered statistically significant.”

With respect to decision-making about biomarker testing, 41% said they prefer to share the responsibility with patients, whereas 52% said they prefer to make the final decision.

“Shedding further light on this situation, focus group participants expressed that patients lacked comprehension and interest about what testing entails and what testing means for their treatment options,” Dr. Boehmer noted.

In order to make more informed decisions about biomarker testing, respondents said they need more information on financial resources for patient assistance (26%) and education around both published guidelines and practical implications of the clinical data (21%).

When asked about patients’ information needs, 23% said their patients need psychosocial support, 22% said they need financial assistance, and 9% said their patients have no additional resource needs.

However, only 27% said they provide patients with resources related to psychosocial support services, and only 44% share financial assistance information, he said.

Further, the fact that 9% said their patients need no additional resources represents “a disconnect” from the findings of the survey and focus groups, he added.

“We believe that this study identifies key areas of ongoing clinician need related to biomarker testing, including things like increased guideline familiarity, practical applications of guideline-concordant testing, and … how to optimally coordinate multidisciplinary care delivery,” Dr. Boehmer said. “Professional organizations … in partnership with patient advocacy organizations or groups should focus on developing those patient education materials … and tools for improving patient-clinician discussions about biomarker testing.”

The ACCC will be working with the LUNGevity Foundation and the Center for Business Models in Healthcare to develop an intervention to ensure that such discussions are “easily integrated into the care process for every patient,” he noted.

Such efforts are important for ensuring that clinicians are informed about the value of biomarker testing and about guidelines for testing so that patients receive the best possible care, said invited discussant Joshua Sabari, MD, of New York University Langone Health’s Perlmutter Cancer Center.

“I know that, in clinic, when meeting a new patient with non–small cell lung cancer, it’s critical to understand the driver alteration, not only for prognosis, but also for goals-of-care discussion, as well as potential treatment option,” Dr. Sabari said.

Dr. Boehmer reported consulting for Pfizer. Dr. Sabari reported consulting and advisory board membership for multiple pharmaceutical companies.

sworcester@mdedge.com

A recent survey shows that fewer than half of community oncologists use biomarker testing to guide patient discussions about treatment, which compares with 73% of academic clinicians.

The findings, reported at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, highlight the potential for unequal application of the latest advances in cancer genomics and targeted therapies throughout the health care system, which could worsen existing disparities in underserved populations, according to Leigh Boehmer, PharmD, medical director for the Association of Community Cancer Centers, Rockville, Md.

The survey – a mixed-methods approach for assessing practice patterns, attitudes, barriers, and resource needs related to biomarker testing among clinicians – was developed by the ACCC in partnership with the LUNGevity Foundation and administered to clinicians caring for patients with non–small cell lung cancer who are uninsured or covered by Medicaid.

Of 99 respondents, more than 85% were physicians and 68% worked in a community setting. Only 40% indicated they were very familiar or extremely familiar with 2018 Molecular Testing Guidelines for Lung Cancer from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.

Clinicians were most confident about selecting appropriate tests to use, interpreting test results, and prognosticating based on test results, with 77%, 74%, and 74%, respectively, saying they are very confident or extremely confident in those areas. They were less confident about determining when to order testing and in coordinating care across the multidisciplinary team, with 59% and 64%, respectively, saying they were very confident or extremely confident in those areas, Dr. Boehmer reported at the conference.

The shortcomings with respect to communication across teams were echoed in two focus groups convened to further validate the survey results, he noted.

As for the reasons why clinicians ordered biomarker testing, 88% and 82% of community and academic clinicians, respectively, said they did so to help make targeted treatment decisions.

“Only 48% of community clinicians indicated that they use biomarker testing to guide patient discussions, compared to 73% of academic clinicians,” he said. “That finding was considered statistically significant.”

With respect to decision-making about biomarker testing, 41% said they prefer to share the responsibility with patients, whereas 52% said they prefer to make the final decision.

“Shedding further light on this situation, focus group participants expressed that patients lacked comprehension and interest about what testing entails and what testing means for their treatment options,” Dr. Boehmer noted.

In order to make more informed decisions about biomarker testing, respondents said they need more information on financial resources for patient assistance (26%) and education around both published guidelines and practical implications of the clinical data (21%).

When asked about patients’ information needs, 23% said their patients need psychosocial support, 22% said they need financial assistance, and 9% said their patients have no additional resource needs.

However, only 27% said they provide patients with resources related to psychosocial support services, and only 44% share financial assistance information, he said.

Further, the fact that 9% said their patients need no additional resources represents “a disconnect” from the findings of the survey and focus groups, he added.

“We believe that this study identifies key areas of ongoing clinician need related to biomarker testing, including things like increased guideline familiarity, practical applications of guideline-concordant testing, and … how to optimally coordinate multidisciplinary care delivery,” Dr. Boehmer said. “Professional organizations … in partnership with patient advocacy organizations or groups should focus on developing those patient education materials … and tools for improving patient-clinician discussions about biomarker testing.”

The ACCC will be working with the LUNGevity Foundation and the Center for Business Models in Healthcare to develop an intervention to ensure that such discussions are “easily integrated into the care process for every patient,” he noted.

Such efforts are important for ensuring that clinicians are informed about the value of biomarker testing and about guidelines for testing so that patients receive the best possible care, said invited discussant Joshua Sabari, MD, of New York University Langone Health’s Perlmutter Cancer Center.

“I know that, in clinic, when meeting a new patient with non–small cell lung cancer, it’s critical to understand the driver alteration, not only for prognosis, but also for goals-of-care discussion, as well as potential treatment option,” Dr. Sabari said.

Dr. Boehmer reported consulting for Pfizer. Dr. Sabari reported consulting and advisory board membership for multiple pharmaceutical companies.

sworcester@mdedge.com

A recent survey shows that fewer than half of community oncologists use biomarker testing to guide patient discussions about treatment, which compares with 73% of academic clinicians.

The findings, reported at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, highlight the potential for unequal application of the latest advances in cancer genomics and targeted therapies throughout the health care system, which could worsen existing disparities in underserved populations, according to Leigh Boehmer, PharmD, medical director for the Association of Community Cancer Centers, Rockville, Md.

The survey – a mixed-methods approach for assessing practice patterns, attitudes, barriers, and resource needs related to biomarker testing among clinicians – was developed by the ACCC in partnership with the LUNGevity Foundation and administered to clinicians caring for patients with non–small cell lung cancer who are uninsured or covered by Medicaid.

Of 99 respondents, more than 85% were physicians and 68% worked in a community setting. Only 40% indicated they were very familiar or extremely familiar with 2018 Molecular Testing Guidelines for Lung Cancer from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.

Clinicians were most confident about selecting appropriate tests to use, interpreting test results, and prognosticating based on test results, with 77%, 74%, and 74%, respectively, saying they are very confident or extremely confident in those areas. They were less confident about determining when to order testing and in coordinating care across the multidisciplinary team, with 59% and 64%, respectively, saying they were very confident or extremely confident in those areas, Dr. Boehmer reported at the conference.

The shortcomings with respect to communication across teams were echoed in two focus groups convened to further validate the survey results, he noted.

As for the reasons why clinicians ordered biomarker testing, 88% and 82% of community and academic clinicians, respectively, said they did so to help make targeted treatment decisions.

“Only 48% of community clinicians indicated that they use biomarker testing to guide patient discussions, compared to 73% of academic clinicians,” he said. “That finding was considered statistically significant.”

With respect to decision-making about biomarker testing, 41% said they prefer to share the responsibility with patients, whereas 52% said they prefer to make the final decision.

“Shedding further light on this situation, focus group participants expressed that patients lacked comprehension and interest about what testing entails and what testing means for their treatment options,” Dr. Boehmer noted.

In order to make more informed decisions about biomarker testing, respondents said they need more information on financial resources for patient assistance (26%) and education around both published guidelines and practical implications of the clinical data (21%).

When asked about patients’ information needs, 23% said their patients need psychosocial support, 22% said they need financial assistance, and 9% said their patients have no additional resource needs.

However, only 27% said they provide patients with resources related to psychosocial support services, and only 44% share financial assistance information, he said.

Further, the fact that 9% said their patients need no additional resources represents “a disconnect” from the findings of the survey and focus groups, he added.

“We believe that this study identifies key areas of ongoing clinician need related to biomarker testing, including things like increased guideline familiarity, practical applications of guideline-concordant testing, and … how to optimally coordinate multidisciplinary care delivery,” Dr. Boehmer said. “Professional organizations … in partnership with patient advocacy organizations or groups should focus on developing those patient education materials … and tools for improving patient-clinician discussions about biomarker testing.”

The ACCC will be working with the LUNGevity Foundation and the Center for Business Models in Healthcare to develop an intervention to ensure that such discussions are “easily integrated into the care process for every patient,” he noted.

Such efforts are important for ensuring that clinicians are informed about the value of biomarker testing and about guidelines for testing so that patients receive the best possible care, said invited discussant Joshua Sabari, MD, of New York University Langone Health’s Perlmutter Cancer Center.

“I know that, in clinic, when meeting a new patient with non–small cell lung cancer, it’s critical to understand the driver alteration, not only for prognosis, but also for goals-of-care discussion, as well as potential treatment option,” Dr. Sabari said.

Dr. Boehmer reported consulting for Pfizer. Dr. Sabari reported consulting and advisory board membership for multiple pharmaceutical companies.

sworcester@mdedge.com

A review of patients with advanced cancer and poor performance status (PS) has shown that objective responses to immunotherapy are rare and that overall survival (OS) is extremely limited. The findings have prompted an expert to argue against the use of immunotherapy for such patients, who may have little time left and very little chance of benefiting.

“It is quite clear from clinical practice that most patients with limited PS do very poorly and do not benefit from immune check point inhibitors (ICI),” Jason Luke, MD, UPMC Hillman Cancer Center and the University of Pittsburgh, said in an email.

“So, my strong opinion is that patients should not be getting an immunotherapy just because it might not cause as many side effects as chemotherapy,” he added.

“Instead of giving an immunotherapy with little chance of success, patients and families deserve to have a direct conversation about what realistic expectations [might be] and how we as the oncology community can support them to achieve whatever their personal goals are in the time that they have left,” he emphasized.

Dr. Luke was the lead author of an editorial in which he commented on the study. Both the study and the editorial were published online in JCO Oncology Practice.
 

Variety of cancers

The study was conducted by Mridula Krishnan, MD, Nebraska Medicine Fred and Pamela Buffett Cancer Center, Omaha, Nebraska, and colleagues.

The team reviewed 257 patients who had been treated with either a programmed cell death protein–1 inhibitor or programmed cell death–ligand-1 inhibitor for a variety of advanced cancers. The drugs included pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentique), durvalumab (Imfinzi), and avelumab (Bavencio).

Most of the patients (71%) had good PS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0-1 on initiation of immunotherapy; 29% of patients had poor PS, with an ECOG PS of greater than or equal to 2.

“The primary outcome was OS stratified by ECOG PS 0-1 versus ≥2,” note the authors. Across all tumor types, OS was superior for patients in the ECOG 0-1 PS group, the investigators note. The median OS was 12.6 months, compared with only 3.1 months for patients in the ECOG greater than or equal to 2 group (P < .001).

Moreover, overall response rates for patients with a poor PS were low. Only 8%, or 6 of 75 patients with an ECOG PS of greater than or equal to 2, achieved an objective response by RECIST criteria.

This compared to an overall response rate of 23% for patients with an ECOG PS of 0-1, the investigators note (P = .005).

Interestingly, the hospice referral rate for patients with a poor PS (67%) was similar to that of patients with a PS of 1-2 (61.9%), Dr. Krishnan and colleagues observe.

Those with a poor PS were more like to die in-hospital (28.6%) than were patients with a good PS (15.1%; P = .035). The authors point out that it is well known that outcomes with chemotherapy are worse among patients who experience a decline in functional reserve, owing to increased susceptibility to toxicity and complications.

“Regardless of age, patients with ECOG PS >2 usually have poor tolerability to chemotherapy, and this correlates with worse survival outcome,” they emphasize. There is as yet no clear guidance regarding the impact of PS on ICI treatment response, although “there should be,” Dr. Luke believes.

“In a patient with declining performance status, especially ECOG PS 3-4 but potentially 2 as well, there is little likelihood that the functional and immune reserve of the patient will be adequate to mount a robust antitumor response,” he elaborated.

“It’s not impossible, but trying for it should not come at the expense of engaging about end-of-life care and maximizing the palliative opportunities that many only have a short window of time in which to pursue,” he added.

Again, Dr. Luke strongly believes that just giving an ICI without engaging in a frank conversation with the patient and their families – which happens all too often, he feels – is absolutely not the way to go when treating patients with a poor PS and little time left.

“Patients and families might be better served by having a more direct and frank conversation about what the likelihood [is] that ICI therapy will actually do,” Dr. Luke stressed.

In their editorial, Dr. Luke and colleagues write: “Overall, we as an oncology community need to improve our communication with patients regarding goals of care and end-of-life considerations as opposed to reflexive treatment initiation,” he writes.

“Our duty, first and foremost, should focus on the person sitting in front of us – taking a step back may be the best way to move forward with compassionate care,” they add.

The authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A review of patients with advanced cancer and poor performance status (PS) has shown that objective responses to immunotherapy are rare and that overall survival (OS) is extremely limited. The findings have prompted an expert to argue against the use of immunotherapy for such patients, who may have little time left and very little chance of benefiting.

“It is quite clear from clinical practice that most patients with limited PS do very poorly and do not benefit from immune check point inhibitors (ICI),” Jason Luke, MD, UPMC Hillman Cancer Center and the University of Pittsburgh, said in an email.

“So, my strong opinion is that patients should not be getting an immunotherapy just because it might not cause as many side effects as chemotherapy,” he added.

“Instead of giving an immunotherapy with little chance of success, patients and families deserve to have a direct conversation about what realistic expectations [might be] and how we as the oncology community can support them to achieve whatever their personal goals are in the time that they have left,” he emphasized.

Dr. Luke was the lead author of an editorial in which he commented on the study. Both the study and the editorial were published online in JCO Oncology Practice.
 

Variety of cancers

The study was conducted by Mridula Krishnan, MD, Nebraska Medicine Fred and Pamela Buffett Cancer Center, Omaha, Nebraska, and colleagues.

The team reviewed 257 patients who had been treated with either a programmed cell death protein–1 inhibitor or programmed cell death–ligand-1 inhibitor for a variety of advanced cancers. The drugs included pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentique), durvalumab (Imfinzi), and avelumab (Bavencio).

Most of the patients (71%) had good PS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0-1 on initiation of immunotherapy; 29% of patients had poor PS, with an ECOG PS of greater than or equal to 2.

“The primary outcome was OS stratified by ECOG PS 0-1 versus ≥2,” note the authors. Across all tumor types, OS was superior for patients in the ECOG 0-1 PS group, the investigators note. The median OS was 12.6 months, compared with only 3.1 months for patients in the ECOG greater than or equal to 2 group (P < .001).

Moreover, overall response rates for patients with a poor PS were low. Only 8%, or 6 of 75 patients with an ECOG PS of greater than or equal to 2, achieved an objective response by RECIST criteria.

This compared to an overall response rate of 23% for patients with an ECOG PS of 0-1, the investigators note (P = .005).

Interestingly, the hospice referral rate for patients with a poor PS (67%) was similar to that of patients with a PS of 1-2 (61.9%), Dr. Krishnan and colleagues observe.

Those with a poor PS were more like to die in-hospital (28.6%) than were patients with a good PS (15.1%; P = .035). The authors point out that it is well known that outcomes with chemotherapy are worse among patients who experience a decline in functional reserve, owing to increased susceptibility to toxicity and complications.

“Regardless of age, patients with ECOG PS >2 usually have poor tolerability to chemotherapy, and this correlates with worse survival outcome,” they emphasize. There is as yet no clear guidance regarding the impact of PS on ICI treatment response, although “there should be,” Dr. Luke believes.

“In a patient with declining performance status, especially ECOG PS 3-4 but potentially 2 as well, there is little likelihood that the functional and immune reserve of the patient will be adequate to mount a robust antitumor response,” he elaborated.

“It’s not impossible, but trying for it should not come at the expense of engaging about end-of-life care and maximizing the palliative opportunities that many only have a short window of time in which to pursue,” he added.

Again, Dr. Luke strongly believes that just giving an ICI without engaging in a frank conversation with the patient and their families – which happens all too often, he feels – is absolutely not the way to go when treating patients with a poor PS and little time left.

“Patients and families might be better served by having a more direct and frank conversation about what the likelihood [is] that ICI therapy will actually do,” Dr. Luke stressed.

In their editorial, Dr. Luke and colleagues write: “Overall, we as an oncology community need to improve our communication with patients regarding goals of care and end-of-life considerations as opposed to reflexive treatment initiation,” he writes.

“Our duty, first and foremost, should focus on the person sitting in front of us – taking a step back may be the best way to move forward with compassionate care,” they add.

The authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A review of patients with advanced cancer and poor performance status (PS) has shown that objective responses to immunotherapy are rare and that overall survival (OS) is extremely limited. The findings have prompted an expert to argue against the use of immunotherapy for such patients, who may have little time left and very little chance of benefiting.

“It is quite clear from clinical practice that most patients with limited PS do very poorly and do not benefit from immune check point inhibitors (ICI),” Jason Luke, MD, UPMC Hillman Cancer Center and the University of Pittsburgh, said in an email.

“So, my strong opinion is that patients should not be getting an immunotherapy just because it might not cause as many side effects as chemotherapy,” he added.

“Instead of giving an immunotherapy with little chance of success, patients and families deserve to have a direct conversation about what realistic expectations [might be] and how we as the oncology community can support them to achieve whatever their personal goals are in the time that they have left,” he emphasized.

Dr. Luke was the lead author of an editorial in which he commented on the study. Both the study and the editorial were published online in JCO Oncology Practice.
 

Variety of cancers

The study was conducted by Mridula Krishnan, MD, Nebraska Medicine Fred and Pamela Buffett Cancer Center, Omaha, Nebraska, and colleagues.

The team reviewed 257 patients who had been treated with either a programmed cell death protein–1 inhibitor or programmed cell death–ligand-1 inhibitor for a variety of advanced cancers. The drugs included pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentique), durvalumab (Imfinzi), and avelumab (Bavencio).

Most of the patients (71%) had good PS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0-1 on initiation of immunotherapy; 29% of patients had poor PS, with an ECOG PS of greater than or equal to 2.

“The primary outcome was OS stratified by ECOG PS 0-1 versus ≥2,” note the authors. Across all tumor types, OS was superior for patients in the ECOG 0-1 PS group, the investigators note. The median OS was 12.6 months, compared with only 3.1 months for patients in the ECOG greater than or equal to 2 group (P < .001).

Moreover, overall response rates for patients with a poor PS were low. Only 8%, or 6 of 75 patients with an ECOG PS of greater than or equal to 2, achieved an objective response by RECIST criteria.

This compared to an overall response rate of 23% for patients with an ECOG PS of 0-1, the investigators note (P = .005).

Interestingly, the hospice referral rate for patients with a poor PS (67%) was similar to that of patients with a PS of 1-2 (61.9%), Dr. Krishnan and colleagues observe.

Those with a poor PS were more like to die in-hospital (28.6%) than were patients with a good PS (15.1%; P = .035). The authors point out that it is well known that outcomes with chemotherapy are worse among patients who experience a decline in functional reserve, owing to increased susceptibility to toxicity and complications.

“Regardless of age, patients with ECOG PS >2 usually have poor tolerability to chemotherapy, and this correlates with worse survival outcome,” they emphasize. There is as yet no clear guidance regarding the impact of PS on ICI treatment response, although “there should be,” Dr. Luke believes.

“In a patient with declining performance status, especially ECOG PS 3-4 but potentially 2 as well, there is little likelihood that the functional and immune reserve of the patient will be adequate to mount a robust antitumor response,” he elaborated.

“It’s not impossible, but trying for it should not come at the expense of engaging about end-of-life care and maximizing the palliative opportunities that many only have a short window of time in which to pursue,” he added.

Again, Dr. Luke strongly believes that just giving an ICI without engaging in a frank conversation with the patient and their families – which happens all too often, he feels – is absolutely not the way to go when treating patients with a poor PS and little time left.

“Patients and families might be better served by having a more direct and frank conversation about what the likelihood [is] that ICI therapy will actually do,” Dr. Luke stressed.

In their editorial, Dr. Luke and colleagues write: “Overall, we as an oncology community need to improve our communication with patients regarding goals of care and end-of-life considerations as opposed to reflexive treatment initiation,” he writes.

“Our duty, first and foremost, should focus on the person sitting in front of us – taking a step back may be the best way to move forward with compassionate care,” they add.

The authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adjuvant pembrolizumab (Keytruda) following complete melanoma resection could soon move to an earlier stage in the management of high-risk disease, suggest results from KEYNOTE-716. However, the results raise many questions, says an expert invited to discuss the new data.

Adjuvant pembrolizumab is already approved in the United States for use in patients with melanoma with lymph node involvement following complete resection, having been shown to prolong both recurrence-free and distant metastasis-free survival (DMFS) in stage 3 melanoma.

This latest trial involved patients with slightly earlier disease, those with resected stage 2B and 2C melanoma. These patients are at “high risk” of disease recurrence and have similar outcomes to stage 3A and 3B melanoma patients, explained study presenter Jason J. Luke, MD, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, Pittsburgh.

Results from the KEYNOTE-716 trial showed that adjuvant pembrolizumab is also beneficial in this earlier stage disease: it improved recurrence-free survival (RFS) by 35% and improved distant metastasis-free survival by 40% compared with placebo.

Adjuvant pembrolizumab is an “effective treatment option with a favorable benefit-risk profile for patients with high-risk stage 2 melanoma,” Dr. Luke concluded.

The manufacturer, Merck, has said that these new results have already been accepted for priority review by the U.S. Food and Drug Administration, making it likely that the indication will be extended to include patients with earlier disease.  

Dr. Luke presented the results at the European Society of Medical Oncology 2021 annual meeting.

Invited discussant Omid Hamid, MD, chief of research/immuno-oncology, the Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, said that Dr. Luke’s presentation was “amazing.”

However, these new results have “sabotaged how we think about how we treat our patients and how we’re going to think about what we do in the future.”

Dr. Hamid noted that the incidence of stage 2B and 2C melanoma is “equal” to that of stage 3 disease, “so with a proposed approval” of pembrolizumab in this earlier setting, “we will have a lot more patients” to treat earlier in their disease course.

Of course, this raises the inevitable question of how to treat these patients when they relapse, and how to treat these patients in the metastatic setting “having already exhausted single-agent PD-1 therapy,” he commented.

Dr. Hamid said that the current results also reveal the “current problem” with adjuvant therapy, which is that “we don’t know who benefits,” and there is a subset patients who “never recur” even if they are untreated.

So the questions are: “How come all get treated? What about the risks of toxicity? The costs? And where do we fit these patients into clinic?”

As with so many presentations of immunotherapy trial data, the need for biomarkers was raised, with Dr. Hamid emphasizing the need for predictive biomarkers that could exclude patients, and save them from toxicity.

He noted that there were data with another checkpoint inhibitor, nivolumab (Opdivo), in the adjuvant setting (from the CheckMate 238 trial) that suggested higher tumor mutation burden and tumor interferon-gamma levels could play a role, and he hopes that similar data may be available from this latest trial.

Also, there are ongoing and upcoming trials in patients with stage 2B and 2C melanoma that may answer some of the outstanding questions, including a study of neoadjuvant PD-1 blockade before resection, and the DETECTION trial, which is exploring circulating tumor DNA-guided therapy postsurgery.

Then there is the NivoMela trial that will look at nivolumab in stage 2A as well as 2B and 2C disease, while the REFINE trial will assess whether giving immunotherapy less often to patients with advanced cancer, including those with melanoma, results in fewer side effects while continuing to be effective.

The current results also raise the question of whether to go “earlier and earlier” with adjuvant immunotherapy into “poor risk” stage 1 melanoma, which is already being tried in the United States, although there is “no clear understanding of what to do for those patients.”

Overall, Dr. Hamid said that the results of KEYNOTE-716 have “created more questions than answers,” including its impact on the inclusion criteria for phase 3/4 clinical trials, “which now exclude patients who have received adjuvant therapy within 6 months.”

“That will have to change,” he suggested.

Some of the questions raised by Dr. Hamid were discussed on social media, sparking a lively Twitter debate on how best to take the results forward and into the clinic.

Florentia Dimitriou, MD, a dermatology consultant in the Skin Cancer Clinic, University Hospital Zurich, Switzerland, said the data were “great” but she was “still unclear” over who needs adjuvant immunotherapy in this setting.

She also emphasized that, for her, the greater RFS benefit seen in T3b than in T4b disease “doesn’t make sense,” and she also highlighted the finding of long-term toxicity in approximately 18% of patients.

Dr. Luke replied that he agrees that the T3b/T4b results are puzzling but he said the event rate was “low” and the data are “immature,” and that he hopes to have “more info soon.”

He acknowledged that around 18% of patients taking pembrolizumab went on to receive hormone therapy for adverse events, including 13.9% due to hypothyroidism, and others including hypophysitis, adrenal sufficiency, and type 1 diabetes. However, he also pointed out that about 5% of patients in this study had background thyroid issues. The risks and benefits of treatment need to be discussed with patients, he added.

Over a series of tweets, Rebecca J. Lee, PhD, NIHR clinical lecturer in medical oncology at the University of Manchester, United Kingdom, said, “we need to know more” about the distant metastasis-free survival results, and that results for overall survival are “really” needed.

She also emphasized the need for biomarkers to identify those patients who are likely to benefit, and whether benefit can be upfront or early on in treatment. Dr. Lee added that, as endocrine thyroid toxicity occurs after a median of 3.3 months, “pretreatment biomarkers will be more important than on-treatment biomarkers in this setting.”

Details of the results in earlier stage disease

The KEYNOTE-716 trial enrolled patients with newly diagnosed, resected, high-risk stage 2 melanoma aged ≥ 12 years and a good performance status. The majority (~64%) had stage 2B melanoma, and the rest had stage 2C. T3b disease was present in 41% of patients, 23% had T4a disease, and 35% had T4b disease.

Patients were randomized to receive pembrolizumab or placebo.

In a subsequent part of the study, patients with recurrence will be unblended, with either crossover from the placebo to active treatment group or rechallenge with pembrolizumab for up to 2 years.

Presenting the first part, Dr. Luke said that, of 487 patients assigned to pembrolizumab, 483 started treatment, of whom 206 have completed treatment, 133 are still on therapy, and 144 have discontinued.

In the placebo group, 489 patients were assigned and 486 began treatment. Of those, 229 completed treatment, 152 are still ongoing, and 105 discontinued.

The two groups were well balanced in terms of baseline characteristics. The median age was approximately 60 years, with only one patient enrolled who was aged 12-17 years.

At 12 months, the study met its primary endpoint.

Relapse-fee survival was 90.5% in patients treated with pembrolizumab versus 83.1% in the placebo group, at a hazard ratio for recurrence of 0.65 (P = .00658).

“Despite this trial hitting this primary endpoint very early, there are a number of patients who are censored later in the curves,” Dr. Luke said, adding that “we will continue to see these data mature.”

“In fact, it’s our full expectation that curves will continue to separate over time.”

When looking at key subgroups, Dr. Luke showed that the results favored pembrolizumab when stratifying patients by age, gender, race, and performance status.

Interestingly, patients with T3b disease did a lot better on pembrolizumab compared with those who had T4b disease, at a hazard ratio for recurrence of 0.44 versus 0.94.

Data on recurrence patterns revealed that 11.1% of patients taking pembrolizumab had an event, with 6.4% experiencing skin and/or lymph node regional recurrence and 4.7% distant recurrence.

In the placebo group, 16.8% of patients had a recurrence event, with 8.4% having a loco-regional recurrence and 7.8% a distant recurrence.

Dr. Luke explained that this equates to an approximate 40% reduction in distant recurrence with pembrolizumab over placebo.

Finally, the researchers examined change in global health status on the EORTC QLQ-C30 quality of life score. Examining mean change over time, they found that there were no clinically meaningful changes, and the scores in the pembrolizumab and placebo groups tracked each other during the course of follow-up.

Quality of life was, therefore, “only minimally changed,” Dr. Luke said.

The study was funded by MSD. Dr. Luke and Dr. Hamid have declared relationships with multiple companies.

A version of this article first appeared on Medscape.com.

Adjuvant pembrolizumab (Keytruda) following complete melanoma resection could soon move to an earlier stage in the management of high-risk disease, suggest results from KEYNOTE-716. However, the results raise many questions, says an expert invited to discuss the new data.

Adjuvant pembrolizumab is already approved in the United States for use in patients with melanoma with lymph node involvement following complete resection, having been shown to prolong both recurrence-free and distant metastasis-free survival (DMFS) in stage 3 melanoma.

This latest trial involved patients with slightly earlier disease, those with resected stage 2B and 2C melanoma. These patients are at “high risk” of disease recurrence and have similar outcomes to stage 3A and 3B melanoma patients, explained study presenter Jason J. Luke, MD, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, Pittsburgh.

Results from the KEYNOTE-716 trial showed that adjuvant pembrolizumab is also beneficial in this earlier stage disease: it improved recurrence-free survival (RFS) by 35% and improved distant metastasis-free survival by 40% compared with placebo.

Adjuvant pembrolizumab is an “effective treatment option with a favorable benefit-risk profile for patients with high-risk stage 2 melanoma,” Dr. Luke concluded.

The manufacturer, Merck, has said that these new results have already been accepted for priority review by the U.S. Food and Drug Administration, making it likely that the indication will be extended to include patients with earlier disease.  

Dr. Luke presented the results at the European Society of Medical Oncology 2021 annual meeting.

Invited discussant Omid Hamid, MD, chief of research/immuno-oncology, the Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, said that Dr. Luke’s presentation was “amazing.”

However, these new results have “sabotaged how we think about how we treat our patients and how we’re going to think about what we do in the future.”

Dr. Hamid noted that the incidence of stage 2B and 2C melanoma is “equal” to that of stage 3 disease, “so with a proposed approval” of pembrolizumab in this earlier setting, “we will have a lot more patients” to treat earlier in their disease course.

Of course, this raises the inevitable question of how to treat these patients when they relapse, and how to treat these patients in the metastatic setting “having already exhausted single-agent PD-1 therapy,” he commented.

Dr. Hamid said that the current results also reveal the “current problem” with adjuvant therapy, which is that “we don’t know who benefits,” and there is a subset patients who “never recur” even if they are untreated.

So the questions are: “How come all get treated? What about the risks of toxicity? The costs? And where do we fit these patients into clinic?”

As with so many presentations of immunotherapy trial data, the need for biomarkers was raised, with Dr. Hamid emphasizing the need for predictive biomarkers that could exclude patients, and save them from toxicity.

He noted that there were data with another checkpoint inhibitor, nivolumab (Opdivo), in the adjuvant setting (from the CheckMate 238 trial) that suggested higher tumor mutation burden and tumor interferon-gamma levels could play a role, and he hopes that similar data may be available from this latest trial.

Also, there are ongoing and upcoming trials in patients with stage 2B and 2C melanoma that may answer some of the outstanding questions, including a study of neoadjuvant PD-1 blockade before resection, and the DETECTION trial, which is exploring circulating tumor DNA-guided therapy postsurgery.

Then there is the NivoMela trial that will look at nivolumab in stage 2A as well as 2B and 2C disease, while the REFINE trial will assess whether giving immunotherapy less often to patients with advanced cancer, including those with melanoma, results in fewer side effects while continuing to be effective.

The current results also raise the question of whether to go “earlier and earlier” with adjuvant immunotherapy into “poor risk” stage 1 melanoma, which is already being tried in the United States, although there is “no clear understanding of what to do for those patients.”

Overall, Dr. Hamid said that the results of KEYNOTE-716 have “created more questions than answers,” including its impact on the inclusion criteria for phase 3/4 clinical trials, “which now exclude patients who have received adjuvant therapy within 6 months.”

“That will have to change,” he suggested.

Some of the questions raised by Dr. Hamid were discussed on social media, sparking a lively Twitter debate on how best to take the results forward and into the clinic.

Florentia Dimitriou, MD, a dermatology consultant in the Skin Cancer Clinic, University Hospital Zurich, Switzerland, said the data were “great” but she was “still unclear” over who needs adjuvant immunotherapy in this setting.

She also emphasized that, for her, the greater RFS benefit seen in T3b than in T4b disease “doesn’t make sense,” and she also highlighted the finding of long-term toxicity in approximately 18% of patients.

Dr. Luke replied that he agrees that the T3b/T4b results are puzzling but he said the event rate was “low” and the data are “immature,” and that he hopes to have “more info soon.”

He acknowledged that around 18% of patients taking pembrolizumab went on to receive hormone therapy for adverse events, including 13.9% due to hypothyroidism, and others including hypophysitis, adrenal sufficiency, and type 1 diabetes. However, he also pointed out that about 5% of patients in this study had background thyroid issues. The risks and benefits of treatment need to be discussed with patients, he added.

Over a series of tweets, Rebecca J. Lee, PhD, NIHR clinical lecturer in medical oncology at the University of Manchester, United Kingdom, said, “we need to know more” about the distant metastasis-free survival results, and that results for overall survival are “really” needed.

She also emphasized the need for biomarkers to identify those patients who are likely to benefit, and whether benefit can be upfront or early on in treatment. Dr. Lee added that, as endocrine thyroid toxicity occurs after a median of 3.3 months, “pretreatment biomarkers will be more important than on-treatment biomarkers in this setting.”

Details of the results in earlier stage disease

The KEYNOTE-716 trial enrolled patients with newly diagnosed, resected, high-risk stage 2 melanoma aged ≥ 12 years and a good performance status. The majority (~64%) had stage 2B melanoma, and the rest had stage 2C. T3b disease was present in 41% of patients, 23% had T4a disease, and 35% had T4b disease.

Patients were randomized to receive pembrolizumab or placebo.

In a subsequent part of the study, patients with recurrence will be unblended, with either crossover from the placebo to active treatment group or rechallenge with pembrolizumab for up to 2 years.

Presenting the first part, Dr. Luke said that, of 487 patients assigned to pembrolizumab, 483 started treatment, of whom 206 have completed treatment, 133 are still on therapy, and 144 have discontinued.

In the placebo group, 489 patients were assigned and 486 began treatment. Of those, 229 completed treatment, 152 are still ongoing, and 105 discontinued.

The two groups were well balanced in terms of baseline characteristics. The median age was approximately 60 years, with only one patient enrolled who was aged 12-17 years.

At 12 months, the study met its primary endpoint.

Relapse-fee survival was 90.5% in patients treated with pembrolizumab versus 83.1% in the placebo group, at a hazard ratio for recurrence of 0.65 (P = .00658).

“Despite this trial hitting this primary endpoint very early, there are a number of patients who are censored later in the curves,” Dr. Luke said, adding that “we will continue to see these data mature.”

“In fact, it’s our full expectation that curves will continue to separate over time.”

When looking at key subgroups, Dr. Luke showed that the results favored pembrolizumab when stratifying patients by age, gender, race, and performance status.

Interestingly, patients with T3b disease did a lot better on pembrolizumab compared with those who had T4b disease, at a hazard ratio for recurrence of 0.44 versus 0.94.

Data on recurrence patterns revealed that 11.1% of patients taking pembrolizumab had an event, with 6.4% experiencing skin and/or lymph node regional recurrence and 4.7% distant recurrence.

In the placebo group, 16.8% of patients had a recurrence event, with 8.4% having a loco-regional recurrence and 7.8% a distant recurrence.

Dr. Luke explained that this equates to an approximate 40% reduction in distant recurrence with pembrolizumab over placebo.

Finally, the researchers examined change in global health status on the EORTC QLQ-C30 quality of life score. Examining mean change over time, they found that there were no clinically meaningful changes, and the scores in the pembrolizumab and placebo groups tracked each other during the course of follow-up.

Quality of life was, therefore, “only minimally changed,” Dr. Luke said.

The study was funded by MSD. Dr. Luke and Dr. Hamid have declared relationships with multiple companies.

A version of this article first appeared on Medscape.com.

Adjuvant pembrolizumab (Keytruda) following complete melanoma resection could soon move to an earlier stage in the management of high-risk disease, suggest results from KEYNOTE-716. However, the results raise many questions, says an expert invited to discuss the new data.

Adjuvant pembrolizumab is already approved in the United States for use in patients with melanoma with lymph node involvement following complete resection, having been shown to prolong both recurrence-free and distant metastasis-free survival (DMFS) in stage 3 melanoma.

This latest trial involved patients with slightly earlier disease, those with resected stage 2B and 2C melanoma. These patients are at “high risk” of disease recurrence and have similar outcomes to stage 3A and 3B melanoma patients, explained study presenter Jason J. Luke, MD, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, Pittsburgh.

Results from the KEYNOTE-716 trial showed that adjuvant pembrolizumab is also beneficial in this earlier stage disease: it improved recurrence-free survival (RFS) by 35% and improved distant metastasis-free survival by 40% compared with placebo.

Adjuvant pembrolizumab is an “effective treatment option with a favorable benefit-risk profile for patients with high-risk stage 2 melanoma,” Dr. Luke concluded.

The manufacturer, Merck, has said that these new results have already been accepted for priority review by the U.S. Food and Drug Administration, making it likely that the indication will be extended to include patients with earlier disease.  

Dr. Luke presented the results at the European Society of Medical Oncology 2021 annual meeting.

Invited discussant Omid Hamid, MD, chief of research/immuno-oncology, the Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, said that Dr. Luke’s presentation was “amazing.”

However, these new results have “sabotaged how we think about how we treat our patients and how we’re going to think about what we do in the future.”

Dr. Hamid noted that the incidence of stage 2B and 2C melanoma is “equal” to that of stage 3 disease, “so with a proposed approval” of pembrolizumab in this earlier setting, “we will have a lot more patients” to treat earlier in their disease course.

Of course, this raises the inevitable question of how to treat these patients when they relapse, and how to treat these patients in the metastatic setting “having already exhausted single-agent PD-1 therapy,” he commented.

Dr. Hamid said that the current results also reveal the “current problem” with adjuvant therapy, which is that “we don’t know who benefits,” and there is a subset patients who “never recur” even if they are untreated.

So the questions are: “How come all get treated? What about the risks of toxicity? The costs? And where do we fit these patients into clinic?”

As with so many presentations of immunotherapy trial data, the need for biomarkers was raised, with Dr. Hamid emphasizing the need for predictive biomarkers that could exclude patients, and save them from toxicity.

He noted that there were data with another checkpoint inhibitor, nivolumab (Opdivo), in the adjuvant setting (from the CheckMate 238 trial) that suggested higher tumor mutation burden and tumor interferon-gamma levels could play a role, and he hopes that similar data may be available from this latest trial.

Also, there are ongoing and upcoming trials in patients with stage 2B and 2C melanoma that may answer some of the outstanding questions, including a study of neoadjuvant PD-1 blockade before resection, and the DETECTION trial, which is exploring circulating tumor DNA-guided therapy postsurgery.

Then there is the NivoMela trial that will look at nivolumab in stage 2A as well as 2B and 2C disease, while the REFINE trial will assess whether giving immunotherapy less often to patients with advanced cancer, including those with melanoma, results in fewer side effects while continuing to be effective.

The current results also raise the question of whether to go “earlier and earlier” with adjuvant immunotherapy into “poor risk” stage 1 melanoma, which is already being tried in the United States, although there is “no clear understanding of what to do for those patients.”

Overall, Dr. Hamid said that the results of KEYNOTE-716 have “created more questions than answers,” including its impact on the inclusion criteria for phase 3/4 clinical trials, “which now exclude patients who have received adjuvant therapy within 6 months.”

“That will have to change,” he suggested.

Some of the questions raised by Dr. Hamid were discussed on social media, sparking a lively Twitter debate on how best to take the results forward and into the clinic.

Florentia Dimitriou, MD, a dermatology consultant in the Skin Cancer Clinic, University Hospital Zurich, Switzerland, said the data were “great” but she was “still unclear” over who needs adjuvant immunotherapy in this setting.

She also emphasized that, for her, the greater RFS benefit seen in T3b than in T4b disease “doesn’t make sense,” and she also highlighted the finding of long-term toxicity in approximately 18% of patients.

Dr. Luke replied that he agrees that the T3b/T4b results are puzzling but he said the event rate was “low” and the data are “immature,” and that he hopes to have “more info soon.”

He acknowledged that around 18% of patients taking pembrolizumab went on to receive hormone therapy for adverse events, including 13.9% due to hypothyroidism, and others including hypophysitis, adrenal sufficiency, and type 1 diabetes. However, he also pointed out that about 5% of patients in this study had background thyroid issues. The risks and benefits of treatment need to be discussed with patients, he added.

Over a series of tweets, Rebecca J. Lee, PhD, NIHR clinical lecturer in medical oncology at the University of Manchester, United Kingdom, said, “we need to know more” about the distant metastasis-free survival results, and that results for overall survival are “really” needed.

She also emphasized the need for biomarkers to identify those patients who are likely to benefit, and whether benefit can be upfront or early on in treatment. Dr. Lee added that, as endocrine thyroid toxicity occurs after a median of 3.3 months, “pretreatment biomarkers will be more important than on-treatment biomarkers in this setting.”

Details of the results in earlier stage disease

The KEYNOTE-716 trial enrolled patients with newly diagnosed, resected, high-risk stage 2 melanoma aged ≥ 12 years and a good performance status. The majority (~64%) had stage 2B melanoma, and the rest had stage 2C. T3b disease was present in 41% of patients, 23% had T4a disease, and 35% had T4b disease.

Patients were randomized to receive pembrolizumab or placebo.

In a subsequent part of the study, patients with recurrence will be unblended, with either crossover from the placebo to active treatment group or rechallenge with pembrolizumab for up to 2 years.

Presenting the first part, Dr. Luke said that, of 487 patients assigned to pembrolizumab, 483 started treatment, of whom 206 have completed treatment, 133 are still on therapy, and 144 have discontinued.

In the placebo group, 489 patients were assigned and 486 began treatment. Of those, 229 completed treatment, 152 are still ongoing, and 105 discontinued.

The two groups were well balanced in terms of baseline characteristics. The median age was approximately 60 years, with only one patient enrolled who was aged 12-17 years.

At 12 months, the study met its primary endpoint.

Relapse-fee survival was 90.5% in patients treated with pembrolizumab versus 83.1% in the placebo group, at a hazard ratio for recurrence of 0.65 (P = .00658).

“Despite this trial hitting this primary endpoint very early, there are a number of patients who are censored later in the curves,” Dr. Luke said, adding that “we will continue to see these data mature.”

“In fact, it’s our full expectation that curves will continue to separate over time.”

When looking at key subgroups, Dr. Luke showed that the results favored pembrolizumab when stratifying patients by age, gender, race, and performance status.

Interestingly, patients with T3b disease did a lot better on pembrolizumab compared with those who had T4b disease, at a hazard ratio for recurrence of 0.44 versus 0.94.

Data on recurrence patterns revealed that 11.1% of patients taking pembrolizumab had an event, with 6.4% experiencing skin and/or lymph node regional recurrence and 4.7% distant recurrence.

In the placebo group, 16.8% of patients had a recurrence event, with 8.4% having a loco-regional recurrence and 7.8% a distant recurrence.

Dr. Luke explained that this equates to an approximate 40% reduction in distant recurrence with pembrolizumab over placebo.

Finally, the researchers examined change in global health status on the EORTC QLQ-C30 quality of life score. Examining mean change over time, they found that there were no clinically meaningful changes, and the scores in the pembrolizumab and placebo groups tracked each other during the course of follow-up.

Quality of life was, therefore, “only minimally changed,” Dr. Luke said.

The study was funded by MSD. Dr. Luke and Dr. Hamid have declared relationships with multiple companies.

A version of this article first appeared on Medscape.com.