AVAHO

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

Some women with the most-difficult-to-treat form of advanced breast cancer who have positively responded to atezolizumab (Tecentriq) are reporting panic and anxiety because oncologists have suddenly discontinued their prescriptions.

The discontinuance appears to be in reaction to an announcement by the manufacturer (Genentech) in late August that it has voluntarily withdrawn its application for accelerated approval of the drug for use in metastatic triple-negative breast cancer (mTNBC).

However, experts stress that discontinuing atezolizumab is not advised if a patient is responding to or is stable on the immune checkpoint inhibitor.

“I think the Genentech announcement has been misinterpreted,” Maryam Lustberg, MD, of Yale Cancer Center, New Haven, Conn., said in an interview. “The consensus opinion from all academic breast oncologists is that people should not be switching off atezolizumab if they are responding. They should not be changing their immunotherapy.”

Dr. Lustberg said the announcement had two major points: “don’t start a new patient on atezolizumab,” and the company is “committed” to supplying the drug to patients whose conditions are stable or responding.

Nevertheless, some patients with mTNBC were recently in a state of escalating emotional upset, said one patient advocate.

“The level of panic among those currently on & responding well to Atezo is growing quickly,” tweeted Janice Cowden on Sept. 5, a former nurse living with mTNBC in Bradenton, Fla.

Ms. Cowden explained that “at least 10-20 patients” were “pulled [off the drug by their oncologists] this past week who have been stable/no evidence of disease/no evidence of disease activity on Tecentriq.”

She estimated that as many as 50 patients in the 2,200-member Triple Negative BC Stage 4 Facebook group who have been responding to the drug were abruptly de-prescribed atezolizumab since the Aug. 27 announcement from Genentech.

Many women learned of the change via patient portals or text messaging, not directly from their physicians, Cowden told Medscape Medical News.

Some of the women had been taking atezolizumab for 2-3 years, including those with no evidence of disease, she said. “Finding out that their oncologist was discontinuing a treatment that was working for them has been driving so much anxiety and stress,” Ms. Cowden emphasized.

Most market withdrawals of drugs are related to safety, but that is not the case with atezolizumab, said Sara Horton, MD, of Howard University, Washington. She was speaking at the recent Facebook webinar on atezolizumab and mTNBC that was sponsored by the TNBC Foundation and the Young Survivors Coalition.

In the case of atezolizumab, it was a question about efficacy that prompted the withdrawal. After the indication was granted an accelerated approval on the basis of response data, a confirmatory trial set out to show clinical benefit. However, the confirmatory phase 3 IMpassion131 trial did not do so: it found that atezolizumab plus paclitaxel did not significantly reduce the risk for cancer progression and death in comparison with paclitaxel plus placebo among patients with TNBC with tumors that were positive for programmed cell death protein–1 (PD-L1), as reported by Medscape Medical News.

These results were discussed by the Food and Drug Administration on the first day of a historic 3-day meeting on accelerated approvals in April 2021. Despite the failure of confirmation of clinical benefit, the advisory panel voted 7-2 in favor of keeping the approval in place for atezolizumab in TNBC. At the same time, it urged Genentech to carry out more studies to show that the drug works in this patient population.

The company apparently decided not to do that and instead voluntarily withdrew the application for the indication some 4 months later.

During the recent TNBC Foundation webinar, Genentech official Lauren Davis said that the company sent letters about this decision to atezolizumab-prescribing physicians and included another letter that was to be shared with patients. Ms. Davis had not responded to this news organization’s request to review the communications at the time this article was published.

At the webinar, Ms. Davis did clarify that current atezolizumab patients (who are responding to the drug), who have commercial insurance, and who benefit from Genentech’s copay program will continue to receive the benefit until June 2022.

In its August announcement, Genentech said it decided to withdraw the atezolizumab approval on the basis of the FDA’s assessment of the “current mTNBC treatment landscape and in accordance with the requirements of the accelerated approval program.”

That landscape presumably includes pembrolizumab (Keytruda), which received a full approval for a TNBC indication similar to that of atezolizumab in July. That full approval was based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen in comparison with neoadjuvant chemotherapy alone for previously untreated stage II or III TNBC. Details of these clinical data will be presented at the upcoming annual meeting of the European Society of Medical Oncology.
 

Switching the immunotherapy?

Some U.S. oncologists have been telling patients with mTNBC that the atezolizumab withdrawal is “not an issue” because the new full approval of pembrolizumab in this setting will allow prescriptions to be switched, said patient advocate Ms. Cowden.

However, experts have said that no patient who is responding to or whose condition is stable with atezolizumab should switch immunotherapies. “This is a very aggressive disease,” reminded Dr. Lustberg.

Switching the immunotherapies is complicated by the difference in the respective drugs’ companion biomarker assays used to establish the presence of PD-L1.

Dr. Lustberg explained that patients who are not responding to atezolizumab and who now want to try pembrolizumab will have to be assessed with the CTS assay.

“About 22% of the patients who are positive for the atezolizumab biomarker assay SP-142 are not going to be positive for the CTS,” she said.

In other words, about one in four patients with mTNBC who are taking atezolizumab will not qualify for treatment with pembrolizumab.

Rebecca Shatsky, MD, of the University of California, San Diego, echoed those comments in an email to this news organization – and emphatically discouraged switching off atezolizumab (and going on pembrolizumab) if a patient is having success (i.e., stable disease or positive response).

“The two groups don’t always overlap, so it isn’t an easy switch. That’s why if they are already responding, I would NOT have them stop the drug,” she said.

Not every mTNBC patient receiving – and responding to – atezolizumab has had the unfortunate experience of having their prescription canceled.

Johanna Rauhala, of San Francisco, who is a former middle-school teacher and who writes the blog Pink Stinks, has been taking atezolizumab for 2 years. She has had a partial response and now, after taking the immunotherapy in combination with chemotherapy (gemcitabine and carboplatin), has stable disease. Currently, she is taking single-agent atezolizumab..

Ms. Rauhala has been living with mTNBC for 5 years. She said in an interview that she was “very surprised and concerned” to learn about Genentech’s withdrawal of its accelerated approval. She said that at her next treatment appointment, she was “probably going to ask the oncology nurse first [about the atezolizumab withdrawal] – because they are the front line, and I will then follow-up with my doctor. But I can’t imagine that they will take away something that is working.”

Dr. Shatsky, Dr. Horton, and Dr. Lunsberg report no relevant financial disclosures.

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

Some women with the most-difficult-to-treat form of advanced breast cancer who have positively responded to atezolizumab (Tecentriq) are reporting panic and anxiety because oncologists have suddenly discontinued their prescriptions.

The discontinuance appears to be in reaction to an announcement by the manufacturer (Genentech) in late August that it has voluntarily withdrawn its application for accelerated approval of the drug for use in metastatic triple-negative breast cancer (mTNBC).

However, experts stress that discontinuing atezolizumab is not advised if a patient is responding to or is stable on the immune checkpoint inhibitor.

“I think the Genentech announcement has been misinterpreted,” Maryam Lustberg, MD, of Yale Cancer Center, New Haven, Conn., said in an interview. “The consensus opinion from all academic breast oncologists is that people should not be switching off atezolizumab if they are responding. They should not be changing their immunotherapy.”

Dr. Lustberg said the announcement had two major points: “don’t start a new patient on atezolizumab,” and the company is “committed” to supplying the drug to patients whose conditions are stable or responding.

Nevertheless, some patients with mTNBC were recently in a state of escalating emotional upset, said one patient advocate.

“The level of panic among those currently on & responding well to Atezo is growing quickly,” tweeted Janice Cowden on Sept. 5, a former nurse living with mTNBC in Bradenton, Fla.

Ms. Cowden explained that “at least 10-20 patients” were “pulled [off the drug by their oncologists] this past week who have been stable/no evidence of disease/no evidence of disease activity on Tecentriq.”

She estimated that as many as 50 patients in the 2,200-member Triple Negative BC Stage 4 Facebook group who have been responding to the drug were abruptly de-prescribed atezolizumab since the Aug. 27 announcement from Genentech.

Many women learned of the change via patient portals or text messaging, not directly from their physicians, Cowden told Medscape Medical News.

Some of the women had been taking atezolizumab for 2-3 years, including those with no evidence of disease, she said. “Finding out that their oncologist was discontinuing a treatment that was working for them has been driving so much anxiety and stress,” Ms. Cowden emphasized.

Most market withdrawals of drugs are related to safety, but that is not the case with atezolizumab, said Sara Horton, MD, of Howard University, Washington. She was speaking at the recent Facebook webinar on atezolizumab and mTNBC that was sponsored by the TNBC Foundation and the Young Survivors Coalition.

In the case of atezolizumab, it was a question about efficacy that prompted the withdrawal. After the indication was granted an accelerated approval on the basis of response data, a confirmatory trial set out to show clinical benefit. However, the confirmatory phase 3 IMpassion131 trial did not do so: it found that atezolizumab plus paclitaxel did not significantly reduce the risk for cancer progression and death in comparison with paclitaxel plus placebo among patients with TNBC with tumors that were positive for programmed cell death protein–1 (PD-L1), as reported by Medscape Medical News.

These results were discussed by the Food and Drug Administration on the first day of a historic 3-day meeting on accelerated approvals in April 2021. Despite the failure of confirmation of clinical benefit, the advisory panel voted 7-2 in favor of keeping the approval in place for atezolizumab in TNBC. At the same time, it urged Genentech to carry out more studies to show that the drug works in this patient population.

The company apparently decided not to do that and instead voluntarily withdrew the application for the indication some 4 months later.

During the recent TNBC Foundation webinar, Genentech official Lauren Davis said that the company sent letters about this decision to atezolizumab-prescribing physicians and included another letter that was to be shared with patients. Ms. Davis had not responded to this news organization’s request to review the communications at the time this article was published.

At the webinar, Ms. Davis did clarify that current atezolizumab patients (who are responding to the drug), who have commercial insurance, and who benefit from Genentech’s copay program will continue to receive the benefit until June 2022.

In its August announcement, Genentech said it decided to withdraw the atezolizumab approval on the basis of the FDA’s assessment of the “current mTNBC treatment landscape and in accordance with the requirements of the accelerated approval program.”

That landscape presumably includes pembrolizumab (Keytruda), which received a full approval for a TNBC indication similar to that of atezolizumab in July. That full approval was based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen in comparison with neoadjuvant chemotherapy alone for previously untreated stage II or III TNBC. Details of these clinical data will be presented at the upcoming annual meeting of the European Society of Medical Oncology.
 

Switching the immunotherapy?

Some U.S. oncologists have been telling patients with mTNBC that the atezolizumab withdrawal is “not an issue” because the new full approval of pembrolizumab in this setting will allow prescriptions to be switched, said patient advocate Ms. Cowden.

However, experts have said that no patient who is responding to or whose condition is stable with atezolizumab should switch immunotherapies. “This is a very aggressive disease,” reminded Dr. Lustberg.

Switching the immunotherapies is complicated by the difference in the respective drugs’ companion biomarker assays used to establish the presence of PD-L1.

Dr. Lustberg explained that patients who are not responding to atezolizumab and who now want to try pembrolizumab will have to be assessed with the CTS assay.

“About 22% of the patients who are positive for the atezolizumab biomarker assay SP-142 are not going to be positive for the CTS,” she said.

In other words, about one in four patients with mTNBC who are taking atezolizumab will not qualify for treatment with pembrolizumab.

Rebecca Shatsky, MD, of the University of California, San Diego, echoed those comments in an email to this news organization – and emphatically discouraged switching off atezolizumab (and going on pembrolizumab) if a patient is having success (i.e., stable disease or positive response).

“The two groups don’t always overlap, so it isn’t an easy switch. That’s why if they are already responding, I would NOT have them stop the drug,” she said.

Not every mTNBC patient receiving – and responding to – atezolizumab has had the unfortunate experience of having their prescription canceled.

Johanna Rauhala, of San Francisco, who is a former middle-school teacher and who writes the blog Pink Stinks, has been taking atezolizumab for 2 years. She has had a partial response and now, after taking the immunotherapy in combination with chemotherapy (gemcitabine and carboplatin), has stable disease. Currently, she is taking single-agent atezolizumab..

Ms. Rauhala has been living with mTNBC for 5 years. She said in an interview that she was “very surprised and concerned” to learn about Genentech’s withdrawal of its accelerated approval. She said that at her next treatment appointment, she was “probably going to ask the oncology nurse first [about the atezolizumab withdrawal] – because they are the front line, and I will then follow-up with my doctor. But I can’t imagine that they will take away something that is working.”

Dr. Shatsky, Dr. Horton, and Dr. Lunsberg report no relevant financial disclosures.

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

Some women with the most-difficult-to-treat form of advanced breast cancer who have positively responded to atezolizumab (Tecentriq) are reporting panic and anxiety because oncologists have suddenly discontinued their prescriptions.

The discontinuance appears to be in reaction to an announcement by the manufacturer (Genentech) in late August that it has voluntarily withdrawn its application for accelerated approval of the drug for use in metastatic triple-negative breast cancer (mTNBC).

However, experts stress that discontinuing atezolizumab is not advised if a patient is responding to or is stable on the immune checkpoint inhibitor.

“I think the Genentech announcement has been misinterpreted,” Maryam Lustberg, MD, of Yale Cancer Center, New Haven, Conn., said in an interview. “The consensus opinion from all academic breast oncologists is that people should not be switching off atezolizumab if they are responding. They should not be changing their immunotherapy.”

Dr. Lustberg said the announcement had two major points: “don’t start a new patient on atezolizumab,” and the company is “committed” to supplying the drug to patients whose conditions are stable or responding.

Nevertheless, some patients with mTNBC were recently in a state of escalating emotional upset, said one patient advocate.

“The level of panic among those currently on & responding well to Atezo is growing quickly,” tweeted Janice Cowden on Sept. 5, a former nurse living with mTNBC in Bradenton, Fla.

Ms. Cowden explained that “at least 10-20 patients” were “pulled [off the drug by their oncologists] this past week who have been stable/no evidence of disease/no evidence of disease activity on Tecentriq.”

She estimated that as many as 50 patients in the 2,200-member Triple Negative BC Stage 4 Facebook group who have been responding to the drug were abruptly de-prescribed atezolizumab since the Aug. 27 announcement from Genentech.

Many women learned of the change via patient portals or text messaging, not directly from their physicians, Cowden told Medscape Medical News.

Some of the women had been taking atezolizumab for 2-3 years, including those with no evidence of disease, she said. “Finding out that their oncologist was discontinuing a treatment that was working for them has been driving so much anxiety and stress,” Ms. Cowden emphasized.

Most market withdrawals of drugs are related to safety, but that is not the case with atezolizumab, said Sara Horton, MD, of Howard University, Washington. She was speaking at the recent Facebook webinar on atezolizumab and mTNBC that was sponsored by the TNBC Foundation and the Young Survivors Coalition.

In the case of atezolizumab, it was a question about efficacy that prompted the withdrawal. After the indication was granted an accelerated approval on the basis of response data, a confirmatory trial set out to show clinical benefit. However, the confirmatory phase 3 IMpassion131 trial did not do so: it found that atezolizumab plus paclitaxel did not significantly reduce the risk for cancer progression and death in comparison with paclitaxel plus placebo among patients with TNBC with tumors that were positive for programmed cell death protein–1 (PD-L1), as reported by Medscape Medical News.

These results were discussed by the Food and Drug Administration on the first day of a historic 3-day meeting on accelerated approvals in April 2021. Despite the failure of confirmation of clinical benefit, the advisory panel voted 7-2 in favor of keeping the approval in place for atezolizumab in TNBC. At the same time, it urged Genentech to carry out more studies to show that the drug works in this patient population.

The company apparently decided not to do that and instead voluntarily withdrew the application for the indication some 4 months later.

During the recent TNBC Foundation webinar, Genentech official Lauren Davis said that the company sent letters about this decision to atezolizumab-prescribing physicians and included another letter that was to be shared with patients. Ms. Davis had not responded to this news organization’s request to review the communications at the time this article was published.

At the webinar, Ms. Davis did clarify that current atezolizumab patients (who are responding to the drug), who have commercial insurance, and who benefit from Genentech’s copay program will continue to receive the benefit until June 2022.

In its August announcement, Genentech said it decided to withdraw the atezolizumab approval on the basis of the FDA’s assessment of the “current mTNBC treatment landscape and in accordance with the requirements of the accelerated approval program.”

That landscape presumably includes pembrolizumab (Keytruda), which received a full approval for a TNBC indication similar to that of atezolizumab in July. That full approval was based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen in comparison with neoadjuvant chemotherapy alone for previously untreated stage II or III TNBC. Details of these clinical data will be presented at the upcoming annual meeting of the European Society of Medical Oncology.
 

Switching the immunotherapy?

Some U.S. oncologists have been telling patients with mTNBC that the atezolizumab withdrawal is “not an issue” because the new full approval of pembrolizumab in this setting will allow prescriptions to be switched, said patient advocate Ms. Cowden.

However, experts have said that no patient who is responding to or whose condition is stable with atezolizumab should switch immunotherapies. “This is a very aggressive disease,” reminded Dr. Lustberg.

Switching the immunotherapies is complicated by the difference in the respective drugs’ companion biomarker assays used to establish the presence of PD-L1.

Dr. Lustberg explained that patients who are not responding to atezolizumab and who now want to try pembrolizumab will have to be assessed with the CTS assay.

“About 22% of the patients who are positive for the atezolizumab biomarker assay SP-142 are not going to be positive for the CTS,” she said.

In other words, about one in four patients with mTNBC who are taking atezolizumab will not qualify for treatment with pembrolizumab.

Rebecca Shatsky, MD, of the University of California, San Diego, echoed those comments in an email to this news organization – and emphatically discouraged switching off atezolizumab (and going on pembrolizumab) if a patient is having success (i.e., stable disease or positive response).

“The two groups don’t always overlap, so it isn’t an easy switch. That’s why if they are already responding, I would NOT have them stop the drug,” she said.

Not every mTNBC patient receiving – and responding to – atezolizumab has had the unfortunate experience of having their prescription canceled.

Johanna Rauhala, of San Francisco, who is a former middle-school teacher and who writes the blog Pink Stinks, has been taking atezolizumab for 2 years. She has had a partial response and now, after taking the immunotherapy in combination with chemotherapy (gemcitabine and carboplatin), has stable disease. Currently, she is taking single-agent atezolizumab..

Ms. Rauhala has been living with mTNBC for 5 years. She said in an interview that she was “very surprised and concerned” to learn about Genentech’s withdrawal of its accelerated approval. She said that at her next treatment appointment, she was “probably going to ask the oncology nurse first [about the atezolizumab withdrawal] – because they are the front line, and I will then follow-up with my doctor. But I can’t imagine that they will take away something that is working.”

Dr. Shatsky, Dr. Horton, and Dr. Lunsberg report no relevant financial disclosures.

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

The U.S. Food and Drug Administration has granted an accelerated approval to mobocertinib (Exkivity, Takeda) for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR Exon 20 insertion mutation detected on an FDA-approved test.

Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer.

“EGFR Exon 20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute, Boston, in a press statement from the maker, Takeda.

“The approval of [mobocertinib] marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses,” Dr. Jänne added.

According to the company, EGFR Exon 20 insertion+ NSCLC makes up approximately 1%-2% of patients with NSCLC and is more common in Asian populations compared with Western populations.

The new approval is based on overall response rate (ORR) and duration of response (DoR) results from a phase 1/2 trial consisting of 114 patients with EGFR Exon 20 insertion+ NSCLC who received prior platinum-based therapy and were treated with the 160-mg dose.

Per an independent review committee, mobocertinib demonstrated a confirmed ORR of 28% and a median DoR of 17.5 months.

Median overall survival was 24 months and median progression-free survival was 7.3 months.

The FDA-approved next-generation sequencing (NGS) companion diagnostic for mobocertinib is Thermo Fisher Scientific’s Oncomine Dx Target Test, which identifies NSCLC patients with EGFR Exon 20 insertions.

“NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon 20 insertions,” according to the company.

Results from the phase 1/2 trial used in the FDA approval were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The most common adverse reactions (greater than 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company.

The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

“Patients with EGFR Exon 20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at the International Cancer Advocacy Network, in the press statement.

The FDA review was conducted under Project Orbis, an FDA initiative that enables concurrent submission and review of oncology products among international partners.

The new drug was also granted priority review and received breakthrough therapy, fast track, and orphan drug designations from the FDA.

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

The U.S. Food and Drug Administration has granted an accelerated approval to mobocertinib (Exkivity, Takeda) for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR Exon 20 insertion mutation detected on an FDA-approved test.

Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer.

“EGFR Exon 20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute, Boston, in a press statement from the maker, Takeda.

“The approval of [mobocertinib] marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses,” Dr. Jänne added.

According to the company, EGFR Exon 20 insertion+ NSCLC makes up approximately 1%-2% of patients with NSCLC and is more common in Asian populations compared with Western populations.

The new approval is based on overall response rate (ORR) and duration of response (DoR) results from a phase 1/2 trial consisting of 114 patients with EGFR Exon 20 insertion+ NSCLC who received prior platinum-based therapy and were treated with the 160-mg dose.

Per an independent review committee, mobocertinib demonstrated a confirmed ORR of 28% and a median DoR of 17.5 months.

Median overall survival was 24 months and median progression-free survival was 7.3 months.

The FDA-approved next-generation sequencing (NGS) companion diagnostic for mobocertinib is Thermo Fisher Scientific’s Oncomine Dx Target Test, which identifies NSCLC patients with EGFR Exon 20 insertions.

“NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon 20 insertions,” according to the company.

Results from the phase 1/2 trial used in the FDA approval were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The most common adverse reactions (greater than 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company.

The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

“Patients with EGFR Exon 20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at the International Cancer Advocacy Network, in the press statement.

The FDA review was conducted under Project Orbis, an FDA initiative that enables concurrent submission and review of oncology products among international partners.

The new drug was also granted priority review and received breakthrough therapy, fast track, and orphan drug designations from the FDA.

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

The U.S. Food and Drug Administration has granted an accelerated approval to mobocertinib (Exkivity, Takeda) for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR Exon 20 insertion mutation detected on an FDA-approved test.

Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer.

“EGFR Exon 20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute, Boston, in a press statement from the maker, Takeda.

“The approval of [mobocertinib] marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses,” Dr. Jänne added.

According to the company, EGFR Exon 20 insertion+ NSCLC makes up approximately 1%-2% of patients with NSCLC and is more common in Asian populations compared with Western populations.

The new approval is based on overall response rate (ORR) and duration of response (DoR) results from a phase 1/2 trial consisting of 114 patients with EGFR Exon 20 insertion+ NSCLC who received prior platinum-based therapy and were treated with the 160-mg dose.

Per an independent review committee, mobocertinib demonstrated a confirmed ORR of 28% and a median DoR of 17.5 months.

Median overall survival was 24 months and median progression-free survival was 7.3 months.

The FDA-approved next-generation sequencing (NGS) companion diagnostic for mobocertinib is Thermo Fisher Scientific’s Oncomine Dx Target Test, which identifies NSCLC patients with EGFR Exon 20 insertions.

“NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon 20 insertions,” according to the company.

Results from the phase 1/2 trial used in the FDA approval were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The most common adverse reactions (greater than 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company.

The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

“Patients with EGFR Exon 20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at the International Cancer Advocacy Network, in the press statement.

The FDA review was conducted under Project Orbis, an FDA initiative that enables concurrent submission and review of oncology products among international partners.

The new drug was also granted priority review and received breakthrough therapy, fast track, and orphan drug designations from the FDA.

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.

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.

Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).

The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.

Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
 

Comparable results

A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).

However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.

“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.

There were no conflicts of interest reported in the article.

mlesney@mdedge.com

Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).

The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.

Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
 

Comparable results

A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).

However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.

“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.

There were no conflicts of interest reported in the article.

mlesney@mdedge.com

Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).

The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.

Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
 

Comparable results

A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).

However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.

“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.

There were no conflicts of interest reported in the article.

mlesney@mdedge.com

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.

The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.

The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.

“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.

Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.

“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”

KEYNOTE-826 details

This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.

The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.

Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).

PFS and OS results

The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.

After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).

The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.

In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).

OS rates were also significantly improved, he noted.

The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).

In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).

Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).

Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.

The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.

Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.

He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.

KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.


A version of this article was first published on Medscape.com.

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.

The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.

The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.

“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.

Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.

“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”

KEYNOTE-826 details

This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.

The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.

Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).

PFS and OS results

The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.

After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).

The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.

In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).

OS rates were also significantly improved, he noted.

The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).

In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).

Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).

Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.

The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.

Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.

He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.

KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.


A version of this article was first published on Medscape.com.

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.

The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.

The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.

“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.

Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.

“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”

KEYNOTE-826 details

This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.

The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.

Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).

PFS and OS results

The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.

After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).

The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.

In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).

OS rates were also significantly improved, he noted.

The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).

In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).

Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).

Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.

The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.

Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.

He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.

KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.


A version of this article was first published on Medscape.com.

Clinicians should pay particular attention to malignant pleural mesothelioma patients with COVID-19. Among people with thoracic malignancies, they have an especially high risk of bad outcomes, according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.

At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.

Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.

The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.

However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.

“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.

Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.

WCLC 2021 was organized by the International Association for the Study of Lung Cancer.

No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.

aotto@mdedge.com

Clinicians should pay particular attention to malignant pleural mesothelioma patients with COVID-19. Among people with thoracic malignancies, they have an especially high risk of bad outcomes, according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.

At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.

Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.

The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.

However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.

“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.

Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.

WCLC 2021 was organized by the International Association for the Study of Lung Cancer.

No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.

aotto@mdedge.com

Clinicians should pay particular attention to malignant pleural mesothelioma patients with COVID-19. Among people with thoracic malignancies, they have an especially high risk of bad outcomes, according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.

At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.

Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.

The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.

However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.

“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.

Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.

WCLC 2021 was organized by the International Association for the Study of Lung Cancer.

No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.

aotto@mdedge.com

Use of antipsychotics that increase prolactin levels is significantly associated with an increased risk for breast cancer in women with schizophrenia, new research suggests. However, at least one expert says that, at this point, clinical implications are premature.

Investigators compared data from Finnish nationwide registers on more than 30,000 women diagnosed with schizophrenia. Of those patients, 1,069 were diagnosed with breast cancer. Results showed that long-term exposure to prolactin-increasing antipsychotics was associated with a 56% increased risk of developing breast cancer in comparison with exposure of short duration. No significant association was found with cumulative exposure to prolactin-sparing antipsychotics.

“In case of planning for long-term antipsychotic [therapy], prefer non–prolactin-raising antipsychotics in females and inform patients about a potential risk to allow for informed shared decision-making,” study coauthor Christoph U. Correll, MD, professor of psychiatry and molecular medicine at Hofstra University, Hempstead, N.Y., told this news organization.

“Monitoring prolactinemia and addressing hyperprolactinemia are important in women with schizophrenia who are treated with prolactin-increasing antipsychotics,” he said.

The study was published online Aug. 30, 2021, in The Lancet.
 

A ‘relevant contribution’

Breast cancer is 25% more prevalent among women with schizophrenia than among women in the general population. Antipsychotics have long been suspected as a potential culprit, but research results have been inconsistent, said Dr. Correll.

In addition, high concentrations of prolactin are associated with a higher risk of developing breast cancer, but most previous research did not distinguish between antipsychotics that increased prolactin levels those that did not.

Dr. Correll and colleagues “wanted to add to this literature by utilizing a generalizable nationwide sample with a sufficient large number of patients and sufficiently long follow-up to address the clinically very relevant question whether antipsychotic use could increase the risk of breast cancer.”

They also believed that grouping antipsychotics into prolactin-raising and non–prolactin-raising agents would be “a relevant contribution.”

The researchers drew on data from several large Finnish databases to conduct a nested case-control study of 30,785 women aged at least16 years who were diagnosed with schizophrenia between 1972 and 2014.

Of these patients, 1,069 received an initial diagnosis of invasive breast cancer (after being diagnosed with schizophrenia) between 2000 and 2017. These case patients were compared to 5,339 matched control patients. The mean age of the case patients and the control patients was 62 years. The mean time since initial diagnosis of schizophrenia was 24 years.

Antipsychotic use was divided into three periods: less than 1 year, 1-4 years, and ≥5 years. Antipsychotics were further divided into prolactin-increasing or prolactin-sparing drugs (for example, clozapine, quetiapine, or aripiprazole). Breast cancer was divided into either lobular or ductal adenocarcinoma.

In their statistical analyses, the researchers adjusted for an array of covariates, including previous diagnoses of other medical conditions, drugs that may modify the risk for breast cancer (for example, beta-blockers, calcium channel blockers, spironolactone, loop diuretics, and statins), substance misuse, suicide attempt, parity, and use of hormone replacement therapy (HRT).
 

‘Clinically meaningful’ risk

Ductal adenocarcinoma was more common than lobular adenocarcinoma (73% vs. 20% among case patients). A higher proportion of case patients used cardiovascular medications and HRT, compared with control patients.

A higher proportion of case patients had used prolactin-increasing antipsychotics for at least 5 years, compared with control patients (71.4% vs. 64.3%; adjusted odds ratio, 1.56; 95% CI, 1.27-1.92; P < .0001) in comparison with minimal exposure (<1 year) to prolactin-increasing antipsychotics.

On the other hand, a similar proportion of case patients and control patients used prolactin-sparing antipsychotics for at least 5 years (8.3 vs. 8.2%; aOR, 1.19; 95% CI, 0.90-1.58); the OR of 1.19 was not deemed significant.

Although exposure of ≥5 years to prolactin-increasing antipsychotics was associated with an increased risk for both types of adenocarcinoma, the risk was higher for lobular than for ductal disease (aOR, 2.36; 95% CI, 1.46-3.82 vs. aOR, 1.42; 95% CI, 1.12-1.80).

“Conservatively, if we subtract the 19% nonsignificantly increased odds with prolactin-sparing antipsychotics from the 56% significantly increased odds with prolactin-increasing antipsychotics, we obtain a 37% relative increase in odds,” the authors noted.

“Using a lifetime incidence of breast cancer in women in the general population of about 12%, with a somewhat higher lifetime incidence in patients with schizophrenia than the general population, this difference between prolactin-increasing versus prolactin-sparing antipsychotics in breast cancer risk upon exposure of 5 or more years would correspond to about a 4% (37% x 12%) increase in absolute breast cancer odds with prolactin-increasing antipsychotic treatment” – a difference the authors call “clinically meaningful.”

Correll noted that although the study was conducted in a Finnish population, the findings are generalizable to other populations.
 

Clinical implications premature?

Commenting on the study, Anton Pottegård, MScPharm, PhD, DMSc, professor of pharmacoepidemiology, department of public health, University of Southern Denmark, Odense, expressed concern that “this new study is fairly aggressive in its recommendation [that] we need to pay attention to hyperprolactinemia, as this seems to cause breast cancer.”

Dr. Pottegård, who is also the head of research, Hospital Pharmacy Funen, Odense University Hospital, who was not involved with the study, said he does not “think that the full body of the literature supports such a direct conclusion and/or direct inference to clinical practice.”

Although “this is an important study to further this work, I do not think we are at a place (yet) where it should lead to different action from clinicians,” Dr. Pottegård cautioned.

Also commenting on the study, Mary Seeman, MDCM, DSc, professor emeritus of neurosciences and clinical translation, department of psychiatry, University of Toronto, called the question of whether prolactin-increasing antipsychotics increase breast cancer risk “very complicated because the incidence of breast cancer ... is higher in women with schizophrenia than in other women.”

Dr. Seeman, who was not involved with the study, pointed to other reasons for the increased risk, including higher rates of obesity, substance abuse, cigarette smoking, stress, and sedentary behavior, all of which raise prolactin levels. Additionally, “protective factors such as pregnancies and breastfeeding are less frequent in women with schizophrenia than in their peers.” Women with schizophrenia also “tend not to do breast screening, see their doctors less often, follow doctors’ orders less rigorously, and obtain treatment less often.”

The take-home message “is to prescribe prolactin-sparing medication to women if at all possible – but until we know more, that is good advice, although not always possible because the illness for which the antipsychotics are prescribed may not respond to those particular medications,” Dr. Seeman said.

The study was funded by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. Funding was also provided to individual researchers by the Academy of Finland, the Finnish Medical Foundation, and the Emil Aaltonen foundation. Dr. Correll has been a consultant or advisor to or has received honoraria from numerous companies. He has provided expert testimony for Janssen and Otsuka; received royalties from UpToDate and is a stock option holder of LB Pharma; served on a data safety monitoring board for Lundbeck, Rovi, Supernus, and Teva; and received grant support from Janssen and Takeda. Dr. Pottegård and Dr. Seeman disclosed no relevant financial relationships.

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

Use of antipsychotics that increase prolactin levels is significantly associated with an increased risk for breast cancer in women with schizophrenia, new research suggests. However, at least one expert says that, at this point, clinical implications are premature.

Investigators compared data from Finnish nationwide registers on more than 30,000 women diagnosed with schizophrenia. Of those patients, 1,069 were diagnosed with breast cancer. Results showed that long-term exposure to prolactin-increasing antipsychotics was associated with a 56% increased risk of developing breast cancer in comparison with exposure of short duration. No significant association was found with cumulative exposure to prolactin-sparing antipsychotics.

“In case of planning for long-term antipsychotic [therapy], prefer non–prolactin-raising antipsychotics in females and inform patients about a potential risk to allow for informed shared decision-making,” study coauthor Christoph U. Correll, MD, professor of psychiatry and molecular medicine at Hofstra University, Hempstead, N.Y., told this news organization.

“Monitoring prolactinemia and addressing hyperprolactinemia are important in women with schizophrenia who are treated with prolactin-increasing antipsychotics,” he said.

The study was published online Aug. 30, 2021, in The Lancet.
 

A ‘relevant contribution’

Breast cancer is 25% more prevalent among women with schizophrenia than among women in the general population. Antipsychotics have long been suspected as a potential culprit, but research results have been inconsistent, said Dr. Correll.

In addition, high concentrations of prolactin are associated with a higher risk of developing breast cancer, but most previous research did not distinguish between antipsychotics that increased prolactin levels those that did not.

Dr. Correll and colleagues “wanted to add to this literature by utilizing a generalizable nationwide sample with a sufficient large number of patients and sufficiently long follow-up to address the clinically very relevant question whether antipsychotic use could increase the risk of breast cancer.”

They also believed that grouping antipsychotics into prolactin-raising and non–prolactin-raising agents would be “a relevant contribution.”

The researchers drew on data from several large Finnish databases to conduct a nested case-control study of 30,785 women aged at least16 years who were diagnosed with schizophrenia between 1972 and 2014.

Of these patients, 1,069 received an initial diagnosis of invasive breast cancer (after being diagnosed with schizophrenia) between 2000 and 2017. These case patients were compared to 5,339 matched control patients. The mean age of the case patients and the control patients was 62 years. The mean time since initial diagnosis of schizophrenia was 24 years.

Antipsychotic use was divided into three periods: less than 1 year, 1-4 years, and ≥5 years. Antipsychotics were further divided into prolactin-increasing or prolactin-sparing drugs (for example, clozapine, quetiapine, or aripiprazole). Breast cancer was divided into either lobular or ductal adenocarcinoma.

In their statistical analyses, the researchers adjusted for an array of covariates, including previous diagnoses of other medical conditions, drugs that may modify the risk for breast cancer (for example, beta-blockers, calcium channel blockers, spironolactone, loop diuretics, and statins), substance misuse, suicide attempt, parity, and use of hormone replacement therapy (HRT).
 

‘Clinically meaningful’ risk

Ductal adenocarcinoma was more common than lobular adenocarcinoma (73% vs. 20% among case patients). A higher proportion of case patients used cardiovascular medications and HRT, compared with control patients.

A higher proportion of case patients had used prolactin-increasing antipsychotics for at least 5 years, compared with control patients (71.4% vs. 64.3%; adjusted odds ratio, 1.56; 95% CI, 1.27-1.92; P < .0001) in comparison with minimal exposure (<1 year) to prolactin-increasing antipsychotics.

On the other hand, a similar proportion of case patients and control patients used prolactin-sparing antipsychotics for at least 5 years (8.3 vs. 8.2%; aOR, 1.19; 95% CI, 0.90-1.58); the OR of 1.19 was not deemed significant.

Although exposure of ≥5 years to prolactin-increasing antipsychotics was associated with an increased risk for both types of adenocarcinoma, the risk was higher for lobular than for ductal disease (aOR, 2.36; 95% CI, 1.46-3.82 vs. aOR, 1.42; 95% CI, 1.12-1.80).

“Conservatively, if we subtract the 19% nonsignificantly increased odds with prolactin-sparing antipsychotics from the 56% significantly increased odds with prolactin-increasing antipsychotics, we obtain a 37% relative increase in odds,” the authors noted.

“Using a lifetime incidence of breast cancer in women in the general population of about 12%, with a somewhat higher lifetime incidence in patients with schizophrenia than the general population, this difference between prolactin-increasing versus prolactin-sparing antipsychotics in breast cancer risk upon exposure of 5 or more years would correspond to about a 4% (37% x 12%) increase in absolute breast cancer odds with prolactin-increasing antipsychotic treatment” – a difference the authors call “clinically meaningful.”

Correll noted that although the study was conducted in a Finnish population, the findings are generalizable to other populations.
 

Clinical implications premature?

Commenting on the study, Anton Pottegård, MScPharm, PhD, DMSc, professor of pharmacoepidemiology, department of public health, University of Southern Denmark, Odense, expressed concern that “this new study is fairly aggressive in its recommendation [that] we need to pay attention to hyperprolactinemia, as this seems to cause breast cancer.”

Dr. Pottegård, who is also the head of research, Hospital Pharmacy Funen, Odense University Hospital, who was not involved with the study, said he does not “think that the full body of the literature supports such a direct conclusion and/or direct inference to clinical practice.”

Although “this is an important study to further this work, I do not think we are at a place (yet) where it should lead to different action from clinicians,” Dr. Pottegård cautioned.

Also commenting on the study, Mary Seeman, MDCM, DSc, professor emeritus of neurosciences and clinical translation, department of psychiatry, University of Toronto, called the question of whether prolactin-increasing antipsychotics increase breast cancer risk “very complicated because the incidence of breast cancer ... is higher in women with schizophrenia than in other women.”

Dr. Seeman, who was not involved with the study, pointed to other reasons for the increased risk, including higher rates of obesity, substance abuse, cigarette smoking, stress, and sedentary behavior, all of which raise prolactin levels. Additionally, “protective factors such as pregnancies and breastfeeding are less frequent in women with schizophrenia than in their peers.” Women with schizophrenia also “tend not to do breast screening, see their doctors less often, follow doctors’ orders less rigorously, and obtain treatment less often.”

The take-home message “is to prescribe prolactin-sparing medication to women if at all possible – but until we know more, that is good advice, although not always possible because the illness for which the antipsychotics are prescribed may not respond to those particular medications,” Dr. Seeman said.

The study was funded by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. Funding was also provided to individual researchers by the Academy of Finland, the Finnish Medical Foundation, and the Emil Aaltonen foundation. Dr. Correll has been a consultant or advisor to or has received honoraria from numerous companies. He has provided expert testimony for Janssen and Otsuka; received royalties from UpToDate and is a stock option holder of LB Pharma; served on a data safety monitoring board for Lundbeck, Rovi, Supernus, and Teva; and received grant support from Janssen and Takeda. Dr. Pottegård and Dr. Seeman disclosed no relevant financial relationships.

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

Use of antipsychotics that increase prolactin levels is significantly associated with an increased risk for breast cancer in women with schizophrenia, new research suggests. However, at least one expert says that, at this point, clinical implications are premature.

Investigators compared data from Finnish nationwide registers on more than 30,000 women diagnosed with schizophrenia. Of those patients, 1,069 were diagnosed with breast cancer. Results showed that long-term exposure to prolactin-increasing antipsychotics was associated with a 56% increased risk of developing breast cancer in comparison with exposure of short duration. No significant association was found with cumulative exposure to prolactin-sparing antipsychotics.

“In case of planning for long-term antipsychotic [therapy], prefer non–prolactin-raising antipsychotics in females and inform patients about a potential risk to allow for informed shared decision-making,” study coauthor Christoph U. Correll, MD, professor of psychiatry and molecular medicine at Hofstra University, Hempstead, N.Y., told this news organization.

“Monitoring prolactinemia and addressing hyperprolactinemia are important in women with schizophrenia who are treated with prolactin-increasing antipsychotics,” he said.

The study was published online Aug. 30, 2021, in The Lancet.
 

A ‘relevant contribution’

Breast cancer is 25% more prevalent among women with schizophrenia than among women in the general population. Antipsychotics have long been suspected as a potential culprit, but research results have been inconsistent, said Dr. Correll.

In addition, high concentrations of prolactin are associated with a higher risk of developing breast cancer, but most previous research did not distinguish between antipsychotics that increased prolactin levels those that did not.

Dr. Correll and colleagues “wanted to add to this literature by utilizing a generalizable nationwide sample with a sufficient large number of patients and sufficiently long follow-up to address the clinically very relevant question whether antipsychotic use could increase the risk of breast cancer.”

They also believed that grouping antipsychotics into prolactin-raising and non–prolactin-raising agents would be “a relevant contribution.”

The researchers drew on data from several large Finnish databases to conduct a nested case-control study of 30,785 women aged at least16 years who were diagnosed with schizophrenia between 1972 and 2014.

Of these patients, 1,069 received an initial diagnosis of invasive breast cancer (after being diagnosed with schizophrenia) between 2000 and 2017. These case patients were compared to 5,339 matched control patients. The mean age of the case patients and the control patients was 62 years. The mean time since initial diagnosis of schizophrenia was 24 years.

Antipsychotic use was divided into three periods: less than 1 year, 1-4 years, and ≥5 years. Antipsychotics were further divided into prolactin-increasing or prolactin-sparing drugs (for example, clozapine, quetiapine, or aripiprazole). Breast cancer was divided into either lobular or ductal adenocarcinoma.

In their statistical analyses, the researchers adjusted for an array of covariates, including previous diagnoses of other medical conditions, drugs that may modify the risk for breast cancer (for example, beta-blockers, calcium channel blockers, spironolactone, loop diuretics, and statins), substance misuse, suicide attempt, parity, and use of hormone replacement therapy (HRT).
 

‘Clinically meaningful’ risk

Ductal adenocarcinoma was more common than lobular adenocarcinoma (73% vs. 20% among case patients). A higher proportion of case patients used cardiovascular medications and HRT, compared with control patients.

A higher proportion of case patients had used prolactin-increasing antipsychotics for at least 5 years, compared with control patients (71.4% vs. 64.3%; adjusted odds ratio, 1.56; 95% CI, 1.27-1.92; P < .0001) in comparison with minimal exposure (<1 year) to prolactin-increasing antipsychotics.

On the other hand, a similar proportion of case patients and control patients used prolactin-sparing antipsychotics for at least 5 years (8.3 vs. 8.2%; aOR, 1.19; 95% CI, 0.90-1.58); the OR of 1.19 was not deemed significant.

Although exposure of ≥5 years to prolactin-increasing antipsychotics was associated with an increased risk for both types of adenocarcinoma, the risk was higher for lobular than for ductal disease (aOR, 2.36; 95% CI, 1.46-3.82 vs. aOR, 1.42; 95% CI, 1.12-1.80).

“Conservatively, if we subtract the 19% nonsignificantly increased odds with prolactin-sparing antipsychotics from the 56% significantly increased odds with prolactin-increasing antipsychotics, we obtain a 37% relative increase in odds,” the authors noted.

“Using a lifetime incidence of breast cancer in women in the general population of about 12%, with a somewhat higher lifetime incidence in patients with schizophrenia than the general population, this difference between prolactin-increasing versus prolactin-sparing antipsychotics in breast cancer risk upon exposure of 5 or more years would correspond to about a 4% (37% x 12%) increase in absolute breast cancer odds with prolactin-increasing antipsychotic treatment” – a difference the authors call “clinically meaningful.”

Correll noted that although the study was conducted in a Finnish population, the findings are generalizable to other populations.
 

Clinical implications premature?

Commenting on the study, Anton Pottegård, MScPharm, PhD, DMSc, professor of pharmacoepidemiology, department of public health, University of Southern Denmark, Odense, expressed concern that “this new study is fairly aggressive in its recommendation [that] we need to pay attention to hyperprolactinemia, as this seems to cause breast cancer.”

Dr. Pottegård, who is also the head of research, Hospital Pharmacy Funen, Odense University Hospital, who was not involved with the study, said he does not “think that the full body of the literature supports such a direct conclusion and/or direct inference to clinical practice.”

Although “this is an important study to further this work, I do not think we are at a place (yet) where it should lead to different action from clinicians,” Dr. Pottegård cautioned.

Also commenting on the study, Mary Seeman, MDCM, DSc, professor emeritus of neurosciences and clinical translation, department of psychiatry, University of Toronto, called the question of whether prolactin-increasing antipsychotics increase breast cancer risk “very complicated because the incidence of breast cancer ... is higher in women with schizophrenia than in other women.”

Dr. Seeman, who was not involved with the study, pointed to other reasons for the increased risk, including higher rates of obesity, substance abuse, cigarette smoking, stress, and sedentary behavior, all of which raise prolactin levels. Additionally, “protective factors such as pregnancies and breastfeeding are less frequent in women with schizophrenia than in their peers.” Women with schizophrenia also “tend not to do breast screening, see their doctors less often, follow doctors’ orders less rigorously, and obtain treatment less often.”

The take-home message “is to prescribe prolactin-sparing medication to women if at all possible – but until we know more, that is good advice, although not always possible because the illness for which the antipsychotics are prescribed may not respond to those particular medications,” Dr. Seeman said.

The study was funded by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. Funding was also provided to individual researchers by the Academy of Finland, the Finnish Medical Foundation, and the Emil Aaltonen foundation. Dr. Correll has been a consultant or advisor to or has received honoraria from numerous companies. He has provided expert testimony for Janssen and Otsuka; received royalties from UpToDate and is a stock option holder of LB Pharma; served on a data safety monitoring board for Lundbeck, Rovi, Supernus, and Teva; and received grant support from Janssen and Takeda. Dr. Pottegård and Dr. Seeman disclosed no relevant financial relationships.

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

Another study has shown an association between antibiotic use and an increased risk for colon cancer.

The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.

Sheep purple/flickr/CC BY 2.0 /en.wikipedia/CC BY-SA 4.0

They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.

In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.

Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).

The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.

The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.

The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.

“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.

In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.

The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.

This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”

A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.

Details of the study findings

For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.

They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.

Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.

The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.

Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).

Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).

Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.

Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).

For distal colon cancer, the relationship was “close to null.”

There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.

The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.

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

Another study has shown an association between antibiotic use and an increased risk for colon cancer.

The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.

Sheep purple/flickr/CC BY 2.0 /en.wikipedia/CC BY-SA 4.0

They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.

In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.

Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).

The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.

The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.

The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.

“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.

In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.

The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.

This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”

A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.

Details of the study findings

For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.

They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.

Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.

The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.

Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).

Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).

Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.

Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).

For distal colon cancer, the relationship was “close to null.”

There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.

The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.

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

Another study has shown an association between antibiotic use and an increased risk for colon cancer.

The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.

Sheep purple/flickr/CC BY 2.0 /en.wikipedia/CC BY-SA 4.0

They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.

In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.

Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).

The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.

The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.

The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.

“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.

In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.

The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.

This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”

A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.

Details of the study findings

For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.

They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.

Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.

The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.

Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).

Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).

Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.

Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).

For distal colon cancer, the relationship was “close to null.”

There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.

The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.

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

Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.

These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.

These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).

Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.

Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.

Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.

These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.

“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.

The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.

Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.

This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.

Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.

Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.

The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.

“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.

However, she expressed concern that “with the telehealth visits, we can create some disparities.”

“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.

Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”

Impact on lung cancer clinical trials

The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.

Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.

The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).

The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.

The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).

Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).

Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).

“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.

Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.

This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).

Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).

The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.

Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.

The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.

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

Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.

These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.

These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).

Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.

Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.

Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.

These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.

“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.

The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.

Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.

This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.

Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.

Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.

The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.

“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.

However, she expressed concern that “with the telehealth visits, we can create some disparities.”

“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.

Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”

Impact on lung cancer clinical trials

The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.

Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.

The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).

The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.

The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).

Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).

Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).

“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.

Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.

This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).

Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).

The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.

Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.

The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.

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

Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.

These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.

These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).

Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.

Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.

Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.

These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.

“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.

The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.

Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.

This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.

Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.

Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.

The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.

“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.

However, she expressed concern that “with the telehealth visits, we can create some disparities.”

“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.

Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”

Impact on lung cancer clinical trials

The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.

Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.

The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).

The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.

The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).

Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).

Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).

“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.

Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.

This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).

Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).

The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.

Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.

The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.

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