Lung Cancer

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

mzoler@mdedge.com

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

mzoler@mdedge.com

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

mzoler@mdedge.com

Low-dose erlotinib is a valid treatment option for elderly and frail patients with non–small cell lung cancer (NSCLC), according to researchers.

They conducted a phase 2 trial to investigate whether one-third of the maximum tolerated dose of erlotinib could maintain sufficient plasma concentration of the drug while avoiding the adverse effects of higher doses. The results were published in JAMA Oncology.

Erlotinib and other epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in elderly patients with EGFR-positive NSCLC, according to study author Shingo Miyamoto, MD, of Japanese Red Cross Medical Center in Tokyo, and colleagues.

“With the increasing number of elderly patients with cancer, many of whom also have significant comorbidities, there is a considerable value in investigating whether EGFR-TKIs are effective for the frail population,” the authors wrote. They also noted that it is “difficult to identify the appropriate dose of molecular-targeted drugs.”

With this in mind, Dr. Miyamoto and colleagues conducted a single-arm, phase 2 trial of low-dose erlotinib in 80 chemotherapy-naive frail or elderly patients with EGFR-positive NSCLC. Frailty was defined by age and the Charlson Comorbidity Index. The patients’ median age was 80 years (range, 49-90 years).

Patients received erlotinib at 50 mg per day, which is one-third of the established maximum tolerated dose, for 4 weeks. Then, they were evaluated with radiologic imaging. Treatment continued until disease progression or unacceptable adverse events. Dosing was modified by treatment response or by adverse events.
 

Results

At last follow-up, 7 of the 80 patients were still receiving low-dose erlotinib. Reasons for discontinuation were disease progression (n = 60), patient request (n = 6), adverse events (n = 4), and death (n = 3).

The overall response rate was 60%, and the disease control rate was 90%. The researchers measured plasma erlotinib concentration in 48 patients and found it did not correlate with response.

The median progression-free survival was 9.3 months, and the median overall survival was 26.2 months.

Ten patients had erlotinib temporarily suspended because of adverse events. Five patients had their dose reduced to 25 mg because of adverse events, including oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia.

Two patients discontinued treatment because of adverse events. One patient had a cutaneous ulcer and bone infection. The other had oral mucositis.

Dr. Miyamoto and colleagues concluded that, “low-dose erlotinib was associated with efficacy and safety in frail patients with EGFR mutation–positive lung cancer. More research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.”
 

Less is more

Sometimes, less can be more, said Mellar P. Davis, MD, an oncologist and section head of the palliative care department at Geisinger Medical System in Danville, Penn., who was not involved in this study.

“Why do patients benefit from small doses? It may be that there are fewer drug interruptions over time and patients are able to stay on schedule,” Dr. Davis said. “It may also be that erlotinib clearance is reduced in the elderly and comorbid patient. The reduced dose may, in fact, be the ‘therapeutic’ dose in this special population.”

Plasma levels were frequently in therapeutic ranges in this study, but patients who had subtherapeutic plasma levels also responded to therapy, Dr. Davis pointed out. The lower dose was shown to maintain sufficient concentrations of the treatment while reducing adverse effects.

However, Dr. Davis noted, this was not a randomized trial. “It is always a risk hedging bets on single-arm trials,” he said. “Randomized trials often prove phase 2 single-arm trials wrong.”

He added that quality-of-life measures are absent from the study. Erlotinib is a palliative drug with side effects, Dr. Davis noted.

“Control of cancer and cancer regression should improve symptoms and quality of life when balanced against treatment toxicity,” he said. “In this study, I would have thought that symptom improvement, performance score, and quality of life would have been the primary outcome or the co-primary outcome with disease control.”

Should a randomized, controlled trial of low-dose erlotinib be conducted in the frail/elderly population? “If one believes trials should be quantitatively based, the answer would be no,” Dr. Davis said. “Responses may be the same, and it would be expensive to prove that low-dose erlotinib is the same as standard doses when comparing survival.”

However, if one is interested in quality of life, particularly in this growing population, a trial that incorporated quality-of-life measures would make more sense, according to Dr. Davis. “For if one can achieve less toxicity and treat more patients and get the same duration of clinical benefit, then less will be more,” he concluded.

Dr. Davis reported having no conflicts of interest. Study authors disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and many other companies. Erlotinib is manufactured for OSI Pharmaceuticals, an affiliate of Astellas Pharma, and distributed by Genentech, a member of the Roche Group.

The study was supported by the Japan Agency for Medical Research and Development.

SOURCE: Miyamoto S et al. JAMA Oncol. 2020 May 14; e201250. doi: 10.1001/jamaoncol.2020.1250.

Low-dose erlotinib is a valid treatment option for elderly and frail patients with non–small cell lung cancer (NSCLC), according to researchers.

They conducted a phase 2 trial to investigate whether one-third of the maximum tolerated dose of erlotinib could maintain sufficient plasma concentration of the drug while avoiding the adverse effects of higher doses. The results were published in JAMA Oncology.

Erlotinib and other epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in elderly patients with EGFR-positive NSCLC, according to study author Shingo Miyamoto, MD, of Japanese Red Cross Medical Center in Tokyo, and colleagues.

“With the increasing number of elderly patients with cancer, many of whom also have significant comorbidities, there is a considerable value in investigating whether EGFR-TKIs are effective for the frail population,” the authors wrote. They also noted that it is “difficult to identify the appropriate dose of molecular-targeted drugs.”

With this in mind, Dr. Miyamoto and colleagues conducted a single-arm, phase 2 trial of low-dose erlotinib in 80 chemotherapy-naive frail or elderly patients with EGFR-positive NSCLC. Frailty was defined by age and the Charlson Comorbidity Index. The patients’ median age was 80 years (range, 49-90 years).

Patients received erlotinib at 50 mg per day, which is one-third of the established maximum tolerated dose, for 4 weeks. Then, they were evaluated with radiologic imaging. Treatment continued until disease progression or unacceptable adverse events. Dosing was modified by treatment response or by adverse events.
 

Results

At last follow-up, 7 of the 80 patients were still receiving low-dose erlotinib. Reasons for discontinuation were disease progression (n = 60), patient request (n = 6), adverse events (n = 4), and death (n = 3).

The overall response rate was 60%, and the disease control rate was 90%. The researchers measured plasma erlotinib concentration in 48 patients and found it did not correlate with response.

The median progression-free survival was 9.3 months, and the median overall survival was 26.2 months.

Ten patients had erlotinib temporarily suspended because of adverse events. Five patients had their dose reduced to 25 mg because of adverse events, including oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia.

Two patients discontinued treatment because of adverse events. One patient had a cutaneous ulcer and bone infection. The other had oral mucositis.

Dr. Miyamoto and colleagues concluded that, “low-dose erlotinib was associated with efficacy and safety in frail patients with EGFR mutation–positive lung cancer. More research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.”
 

Less is more

Sometimes, less can be more, said Mellar P. Davis, MD, an oncologist and section head of the palliative care department at Geisinger Medical System in Danville, Penn., who was not involved in this study.

“Why do patients benefit from small doses? It may be that there are fewer drug interruptions over time and patients are able to stay on schedule,” Dr. Davis said. “It may also be that erlotinib clearance is reduced in the elderly and comorbid patient. The reduced dose may, in fact, be the ‘therapeutic’ dose in this special population.”

Plasma levels were frequently in therapeutic ranges in this study, but patients who had subtherapeutic plasma levels also responded to therapy, Dr. Davis pointed out. The lower dose was shown to maintain sufficient concentrations of the treatment while reducing adverse effects.

However, Dr. Davis noted, this was not a randomized trial. “It is always a risk hedging bets on single-arm trials,” he said. “Randomized trials often prove phase 2 single-arm trials wrong.”

He added that quality-of-life measures are absent from the study. Erlotinib is a palliative drug with side effects, Dr. Davis noted.

“Control of cancer and cancer regression should improve symptoms and quality of life when balanced against treatment toxicity,” he said. “In this study, I would have thought that symptom improvement, performance score, and quality of life would have been the primary outcome or the co-primary outcome with disease control.”

Should a randomized, controlled trial of low-dose erlotinib be conducted in the frail/elderly population? “If one believes trials should be quantitatively based, the answer would be no,” Dr. Davis said. “Responses may be the same, and it would be expensive to prove that low-dose erlotinib is the same as standard doses when comparing survival.”

However, if one is interested in quality of life, particularly in this growing population, a trial that incorporated quality-of-life measures would make more sense, according to Dr. Davis. “For if one can achieve less toxicity and treat more patients and get the same duration of clinical benefit, then less will be more,” he concluded.

Dr. Davis reported having no conflicts of interest. Study authors disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and many other companies. Erlotinib is manufactured for OSI Pharmaceuticals, an affiliate of Astellas Pharma, and distributed by Genentech, a member of the Roche Group.

The study was supported by the Japan Agency for Medical Research and Development.

SOURCE: Miyamoto S et al. JAMA Oncol. 2020 May 14; e201250. doi: 10.1001/jamaoncol.2020.1250.

Low-dose erlotinib is a valid treatment option for elderly and frail patients with non–small cell lung cancer (NSCLC), according to researchers.

They conducted a phase 2 trial to investigate whether one-third of the maximum tolerated dose of erlotinib could maintain sufficient plasma concentration of the drug while avoiding the adverse effects of higher doses. The results were published in JAMA Oncology.

Erlotinib and other epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in elderly patients with EGFR-positive NSCLC, according to study author Shingo Miyamoto, MD, of Japanese Red Cross Medical Center in Tokyo, and colleagues.

“With the increasing number of elderly patients with cancer, many of whom also have significant comorbidities, there is a considerable value in investigating whether EGFR-TKIs are effective for the frail population,” the authors wrote. They also noted that it is “difficult to identify the appropriate dose of molecular-targeted drugs.”

With this in mind, Dr. Miyamoto and colleagues conducted a single-arm, phase 2 trial of low-dose erlotinib in 80 chemotherapy-naive frail or elderly patients with EGFR-positive NSCLC. Frailty was defined by age and the Charlson Comorbidity Index. The patients’ median age was 80 years (range, 49-90 years).

Patients received erlotinib at 50 mg per day, which is one-third of the established maximum tolerated dose, for 4 weeks. Then, they were evaluated with radiologic imaging. Treatment continued until disease progression or unacceptable adverse events. Dosing was modified by treatment response or by adverse events.
 

Results

At last follow-up, 7 of the 80 patients were still receiving low-dose erlotinib. Reasons for discontinuation were disease progression (n = 60), patient request (n = 6), adverse events (n = 4), and death (n = 3).

The overall response rate was 60%, and the disease control rate was 90%. The researchers measured plasma erlotinib concentration in 48 patients and found it did not correlate with response.

The median progression-free survival was 9.3 months, and the median overall survival was 26.2 months.

Ten patients had erlotinib temporarily suspended because of adverse events. Five patients had their dose reduced to 25 mg because of adverse events, including oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia.

Two patients discontinued treatment because of adverse events. One patient had a cutaneous ulcer and bone infection. The other had oral mucositis.

Dr. Miyamoto and colleagues concluded that, “low-dose erlotinib was associated with efficacy and safety in frail patients with EGFR mutation–positive lung cancer. More research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.”
 

Less is more

Sometimes, less can be more, said Mellar P. Davis, MD, an oncologist and section head of the palliative care department at Geisinger Medical System in Danville, Penn., who was not involved in this study.

“Why do patients benefit from small doses? It may be that there are fewer drug interruptions over time and patients are able to stay on schedule,” Dr. Davis said. “It may also be that erlotinib clearance is reduced in the elderly and comorbid patient. The reduced dose may, in fact, be the ‘therapeutic’ dose in this special population.”

Plasma levels were frequently in therapeutic ranges in this study, but patients who had subtherapeutic plasma levels also responded to therapy, Dr. Davis pointed out. The lower dose was shown to maintain sufficient concentrations of the treatment while reducing adverse effects.

However, Dr. Davis noted, this was not a randomized trial. “It is always a risk hedging bets on single-arm trials,” he said. “Randomized trials often prove phase 2 single-arm trials wrong.”

He added that quality-of-life measures are absent from the study. Erlotinib is a palliative drug with side effects, Dr. Davis noted.

“Control of cancer and cancer regression should improve symptoms and quality of life when balanced against treatment toxicity,” he said. “In this study, I would have thought that symptom improvement, performance score, and quality of life would have been the primary outcome or the co-primary outcome with disease control.”

Should a randomized, controlled trial of low-dose erlotinib be conducted in the frail/elderly population? “If one believes trials should be quantitatively based, the answer would be no,” Dr. Davis said. “Responses may be the same, and it would be expensive to prove that low-dose erlotinib is the same as standard doses when comparing survival.”

However, if one is interested in quality of life, particularly in this growing population, a trial that incorporated quality-of-life measures would make more sense, according to Dr. Davis. “For if one can achieve less toxicity and treat more patients and get the same duration of clinical benefit, then less will be more,” he concluded.

Dr. Davis reported having no conflicts of interest. Study authors disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and many other companies. Erlotinib is manufactured for OSI Pharmaceuticals, an affiliate of Astellas Pharma, and distributed by Genentech, a member of the Roche Group.

The study was supported by the Japan Agency for Medical Research and Development.

SOURCE: Miyamoto S et al. JAMA Oncol. 2020 May 14; e201250. doi: 10.1001/jamaoncol.2020.1250.

Oncologists continue to rank above the middle range for all specialties in annual compensation for physicians, according to findings from the newly released Medscape Oncologist Compensation Report 2020.

The average earnings for oncologists who participated in the survey was $377,000, which was a 5% increase from the $359,000 reported for 2018.

Just over two-thirds (67%) of oncologists reported that they felt that they were fairly compensated, which is quite a jump from 53% last year.

In addition, oncologists appear to be very satisfied with their profession. Similar to last year’s findings, 84% said they would choose medicine again, and 96% said they would choose the specialty of oncology again.
 

Earning in top third of all specialties

The average annual earnings reported by oncologists put this specialty in eleventh place among 29 specialties. Orthopedic specialists remain at the head of the list, with estimated earnings of $511,000, followed by plastic surgeons ($479,000), otolaryngologists ($455,000), and cardiologists ($438,000), according to Medscape’s compensation report, which included responses from 17,461 physicians in over 30 specialties.

At the bottom of the estimated earnings list were public health and preventive medicine doctors and pediatricians. For both specialties, the reported annual earnings was $232,000. Family medicine specialists were only marginally higher at $234,000.

Radiologists ($427,000), gastroenterologists ($419,000), and urologists ($417,000) all reported higher earnings than oncologists, whereas neurologists, at $280,000, rheumatologists, at $262,000, and internal medicine physicians, at $251,000, earned less.

The report also found that gender disparities in income persist, with male oncologists earning 17% more than their female colleagues. The gender gap in oncology is somewhat less than that seen for all specialties combined, in which men earned 31% more than women, similar to last year’s figure of 33%.

Male oncologists reported spending 38.8 hours per week seeing patients, compared with 34.9 hours reported by female oncologists. This could be a factor contributing to the gender pay disparity. Overall, the average amount of time seeing patients was 37.9 hours per week.
 

Frustrations with paperwork and denied claims

Surveyed oncologists cited some of the frustrations they are facing, such as spending nearly 17 hours a week on paperwork and administrative tasks. They reported that 16% of claims are denied or have to be resubmitted. As for the most challenging part of the job, oncologists (22%), similar to physicians overall (26%), found that having so many rules and regulations takes first place, followed by working with electronic health record systems (20%), difficulties getting fair reimbursement (19%), having to work long hours (12%), and dealing with difficult patients (8%). Few oncologists were concerned about lawsuits (4%), and 4% reported that there were no challenges.

Oncologists reported that the most rewarding part of their job was gratitude/relationships with patients (31%), followed by knowing that they are making the world a better place (27%). After that, oncologists agreed with statements about being very good at what they do/finding answers/diagnoses (22%), having pride in being a doctor (9%), and making good money at a job they like (8%).
 

Other key findings

Other key findings from the Medscape Oncologist Compensation Report 2020 included the following:

• Regarding payment models, 80% take insurance, 41% are in fee-for-service arrangements, and 18% are in accountable care organizations (21%). Only 3% are in direct primary care, and 1% are cash-only practices or have a concierge practice.
• 65% of oncologists state that they will continue taking new and current Medicare/Medicaid patients. None said that they would not take on new Medicare/Medicaid patients, and 35% remain undecided. These numbers differed from physicians overall; 73% of all physicians surveyed said they would continue taking new/current Medicare/Medicaid patients, 6% said that will not take on new Medicare patients, and 4% said they will not take new Medicaid patients. In addition, 3% and 2% said that they would stop treating some or all of their Medicare and Medicaid patients, respectively.
• About half (51%) of oncologists use nurse practitioners, about a third (34%) use physician assistants, and 37% use neither. This was about the same as physicians overall.
• A larger percentage of oncologists (38%) expect to participate in MIPS (merit-based incentive payment system), and only 8% expect to participate in APMs (alternative payment models). This was similar to the findings for physicians overall, with more than one-third (37%) expecting to participate in MIPS and 9% planning to take part in APMs.

Impact of COVID-19 pandemic

The Medscape compensation reports also gives a glimpse of the impact the COVID-19 pandemic is having on physician compensation.

Since the beginning of the pandemic, practices have reported a 55% decrease in revenue and a 60% drop in patient volume. Physician practices and hospitals have laid off or furloughed personnel and have cut pay, and 9% of practices have closed their doors, at least for the time being.

A total of 43,000 health care workers were laid off in March, the report notes.

The findings tie in with those reported elsewhere. For example, a survey conducted by the Medical Group Management Association, which was reported by Medscape Medical News, found that 97% of physician practices have experienced negative financial effects directly or indirectly related to COVID-19.

Specialties were hard hit, especially those that rely on elective procedures, such as dermatology and cardiology. Oncology care has also been disrupted. For example, a survey conducted by the American Cancer Society Cancer Action Network found that half of the cancer patients and survivors who responded reported changes, delays, or disruptions to the care they were receiving.

This article first appeared on Medscape.com.

Oncologists continue to rank above the middle range for all specialties in annual compensation for physicians, according to findings from the newly released Medscape Oncologist Compensation Report 2020.

The average earnings for oncologists who participated in the survey was $377,000, which was a 5% increase from the $359,000 reported for 2018.

Just over two-thirds (67%) of oncologists reported that they felt that they were fairly compensated, which is quite a jump from 53% last year.

In addition, oncologists appear to be very satisfied with their profession. Similar to last year’s findings, 84% said they would choose medicine again, and 96% said they would choose the specialty of oncology again.
 

Earning in top third of all specialties

The average annual earnings reported by oncologists put this specialty in eleventh place among 29 specialties. Orthopedic specialists remain at the head of the list, with estimated earnings of $511,000, followed by plastic surgeons ($479,000), otolaryngologists ($455,000), and cardiologists ($438,000), according to Medscape’s compensation report, which included responses from 17,461 physicians in over 30 specialties.

At the bottom of the estimated earnings list were public health and preventive medicine doctors and pediatricians. For both specialties, the reported annual earnings was $232,000. Family medicine specialists were only marginally higher at $234,000.

Radiologists ($427,000), gastroenterologists ($419,000), and urologists ($417,000) all reported higher earnings than oncologists, whereas neurologists, at $280,000, rheumatologists, at $262,000, and internal medicine physicians, at $251,000, earned less.

The report also found that gender disparities in income persist, with male oncologists earning 17% more than their female colleagues. The gender gap in oncology is somewhat less than that seen for all specialties combined, in which men earned 31% more than women, similar to last year’s figure of 33%.

Male oncologists reported spending 38.8 hours per week seeing patients, compared with 34.9 hours reported by female oncologists. This could be a factor contributing to the gender pay disparity. Overall, the average amount of time seeing patients was 37.9 hours per week.
 

Frustrations with paperwork and denied claims

Surveyed oncologists cited some of the frustrations they are facing, such as spending nearly 17 hours a week on paperwork and administrative tasks. They reported that 16% of claims are denied or have to be resubmitted. As for the most challenging part of the job, oncologists (22%), similar to physicians overall (26%), found that having so many rules and regulations takes first place, followed by working with electronic health record systems (20%), difficulties getting fair reimbursement (19%), having to work long hours (12%), and dealing with difficult patients (8%). Few oncologists were concerned about lawsuits (4%), and 4% reported that there were no challenges.

Oncologists reported that the most rewarding part of their job was gratitude/relationships with patients (31%), followed by knowing that they are making the world a better place (27%). After that, oncologists agreed with statements about being very good at what they do/finding answers/diagnoses (22%), having pride in being a doctor (9%), and making good money at a job they like (8%).
 

Other key findings

Other key findings from the Medscape Oncologist Compensation Report 2020 included the following:

• Regarding payment models, 80% take insurance, 41% are in fee-for-service arrangements, and 18% are in accountable care organizations (21%). Only 3% are in direct primary care, and 1% are cash-only practices or have a concierge practice.
• 65% of oncologists state that they will continue taking new and current Medicare/Medicaid patients. None said that they would not take on new Medicare/Medicaid patients, and 35% remain undecided. These numbers differed from physicians overall; 73% of all physicians surveyed said they would continue taking new/current Medicare/Medicaid patients, 6% said that will not take on new Medicare patients, and 4% said they will not take new Medicaid patients. In addition, 3% and 2% said that they would stop treating some or all of their Medicare and Medicaid patients, respectively.
• About half (51%) of oncologists use nurse practitioners, about a third (34%) use physician assistants, and 37% use neither. This was about the same as physicians overall.
• A larger percentage of oncologists (38%) expect to participate in MIPS (merit-based incentive payment system), and only 8% expect to participate in APMs (alternative payment models). This was similar to the findings for physicians overall, with more than one-third (37%) expecting to participate in MIPS and 9% planning to take part in APMs.

Impact of COVID-19 pandemic

The Medscape compensation reports also gives a glimpse of the impact the COVID-19 pandemic is having on physician compensation.

Since the beginning of the pandemic, practices have reported a 55% decrease in revenue and a 60% drop in patient volume. Physician practices and hospitals have laid off or furloughed personnel and have cut pay, and 9% of practices have closed their doors, at least for the time being.

A total of 43,000 health care workers were laid off in March, the report notes.

The findings tie in with those reported elsewhere. For example, a survey conducted by the Medical Group Management Association, which was reported by Medscape Medical News, found that 97% of physician practices have experienced negative financial effects directly or indirectly related to COVID-19.

Specialties were hard hit, especially those that rely on elective procedures, such as dermatology and cardiology. Oncology care has also been disrupted. For example, a survey conducted by the American Cancer Society Cancer Action Network found that half of the cancer patients and survivors who responded reported changes, delays, or disruptions to the care they were receiving.

This article first appeared on Medscape.com.

Oncologists continue to rank above the middle range for all specialties in annual compensation for physicians, according to findings from the newly released Medscape Oncologist Compensation Report 2020.

The average earnings for oncologists who participated in the survey was $377,000, which was a 5% increase from the $359,000 reported for 2018.

Just over two-thirds (67%) of oncologists reported that they felt that they were fairly compensated, which is quite a jump from 53% last year.

In addition, oncologists appear to be very satisfied with their profession. Similar to last year’s findings, 84% said they would choose medicine again, and 96% said they would choose the specialty of oncology again.
 

Earning in top third of all specialties

The average annual earnings reported by oncologists put this specialty in eleventh place among 29 specialties. Orthopedic specialists remain at the head of the list, with estimated earnings of $511,000, followed by plastic surgeons ($479,000), otolaryngologists ($455,000), and cardiologists ($438,000), according to Medscape’s compensation report, which included responses from 17,461 physicians in over 30 specialties.

At the bottom of the estimated earnings list were public health and preventive medicine doctors and pediatricians. For both specialties, the reported annual earnings was $232,000. Family medicine specialists were only marginally higher at $234,000.

Radiologists ($427,000), gastroenterologists ($419,000), and urologists ($417,000) all reported higher earnings than oncologists, whereas neurologists, at $280,000, rheumatologists, at $262,000, and internal medicine physicians, at $251,000, earned less.

The report also found that gender disparities in income persist, with male oncologists earning 17% more than their female colleagues. The gender gap in oncology is somewhat less than that seen for all specialties combined, in which men earned 31% more than women, similar to last year’s figure of 33%.

Male oncologists reported spending 38.8 hours per week seeing patients, compared with 34.9 hours reported by female oncologists. This could be a factor contributing to the gender pay disparity. Overall, the average amount of time seeing patients was 37.9 hours per week.
 

Frustrations with paperwork and denied claims

Surveyed oncologists cited some of the frustrations they are facing, such as spending nearly 17 hours a week on paperwork and administrative tasks. They reported that 16% of claims are denied or have to be resubmitted. As for the most challenging part of the job, oncologists (22%), similar to physicians overall (26%), found that having so many rules and regulations takes first place, followed by working with electronic health record systems (20%), difficulties getting fair reimbursement (19%), having to work long hours (12%), and dealing with difficult patients (8%). Few oncologists were concerned about lawsuits (4%), and 4% reported that there were no challenges.

Oncologists reported that the most rewarding part of their job was gratitude/relationships with patients (31%), followed by knowing that they are making the world a better place (27%). After that, oncologists agreed with statements about being very good at what they do/finding answers/diagnoses (22%), having pride in being a doctor (9%), and making good money at a job they like (8%).
 

Other key findings

Other key findings from the Medscape Oncologist Compensation Report 2020 included the following:

• Regarding payment models, 80% take insurance, 41% are in fee-for-service arrangements, and 18% are in accountable care organizations (21%). Only 3% are in direct primary care, and 1% are cash-only practices or have a concierge practice.
• 65% of oncologists state that they will continue taking new and current Medicare/Medicaid patients. None said that they would not take on new Medicare/Medicaid patients, and 35% remain undecided. These numbers differed from physicians overall; 73% of all physicians surveyed said they would continue taking new/current Medicare/Medicaid patients, 6% said that will not take on new Medicare patients, and 4% said they will not take new Medicaid patients. In addition, 3% and 2% said that they would stop treating some or all of their Medicare and Medicaid patients, respectively.
• About half (51%) of oncologists use nurse practitioners, about a third (34%) use physician assistants, and 37% use neither. This was about the same as physicians overall.
• A larger percentage of oncologists (38%) expect to participate in MIPS (merit-based incentive payment system), and only 8% expect to participate in APMs (alternative payment models). This was similar to the findings for physicians overall, with more than one-third (37%) expecting to participate in MIPS and 9% planning to take part in APMs.

Impact of COVID-19 pandemic

The Medscape compensation reports also gives a glimpse of the impact the COVID-19 pandemic is having on physician compensation.

Since the beginning of the pandemic, practices have reported a 55% decrease in revenue and a 60% drop in patient volume. Physician practices and hospitals have laid off or furloughed personnel and have cut pay, and 9% of practices have closed their doors, at least for the time being.

A total of 43,000 health care workers were laid off in March, the report notes.

The findings tie in with those reported elsewhere. For example, a survey conducted by the Medical Group Management Association, which was reported by Medscape Medical News, found that 97% of physician practices have experienced negative financial effects directly or indirectly related to COVID-19.

Specialties were hard hit, especially those that rely on elective procedures, such as dermatology and cardiology. Oncology care has also been disrupted. For example, a survey conducted by the American Cancer Society Cancer Action Network found that half of the cancer patients and survivors who responded reported changes, delays, or disruptions to the care they were receiving.

This article first appeared on Medscape.com.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

Virtually all oncologists, at one time or another, have treated a patient who defied the odds and achieved an unexpectedly long-lasting response. These “exceptional responders” are patients who experience a unique response to therapies that have largely failed to be effective for others with similar cancers.

Genetic and molecular mechanisms may partly account for these responses and may offer clues about why the treatment works for only a few and not for others. To delve more deeply into that area of research, the National Cancer Institute (NCI) began the Exceptional Responders Initiative (ERI) with the goal of identifying potential biological processes that may be responsible, at least in part, for these unusual responses.

NCI researchers have now successfully completed a pilot study that analyzed tumor specimens from more than 100 cases, and the study has affirmed the feasibility of this approach.

Of these cases, six were identified as involving potentially clinically actionable germline mutations.

The findings were published online ahead of print in the Journal of the National Cancer Institute.

“Clearly, the analysis and validation of these results will prove critical to determining the success of this approach,” write James M. Ford, MD, and Beverly S. Mitchell, MD, both of Stanford University School of Medicine, California, in an accompanying editorial. “Ultimately, prospective studies of tumors from exceptional responders, particularly to novel, genomically-targeted agents, may provide a powerful approach to cancer treatment discoveries.”
 

A special case

Molecular profiling technology, including next-generation sequencing, has significantly changed the landscape of the development of cancer therapies, and clinical trials in early drug development are increasingly selecting patients on the basis of molecular alterations.

The ERI grew out of several meetings held by the NCI in 2013 and 2014. It was built on the ability to profile archived tumor material, explained study author S. Percy Ivy, PhD, associate chief of the Investigational Drug Branch in the Division of Cancer Treatment and Diagnosis of the NCI. “This made it possible to collect cases from participating clinicians from all over the country.

“Published cases included patients treated with a targeted therapy but not treated with knowledge of their tumor’s genomics, who then later turned out to have genomic changes that made their tumor exquisitely sensitive to inhibition of a driving pathway,” she said. “There have been published cases as well as cases in the experience of practicing oncologists that seem to do much better than expected.

“We wondered if we could find molecular reasons why tumors respond not only to targeted therapies but also to standard chemotherapy,” said Percy. “If so, we could refine our choice of therapy to patients who are most likely to respond to it.”’

On its website, the NCI writes that there was a particular case that triggered the interest in going ahead with this initiative. Mutations in the TSC1 and NF2 genes, which result in a loss of gene function, were detected in a patient with metastatic bladder cancer. In a clinical trial, the patient was treated with everolimus (Afinitor, Novartis), an inhibitor of the mammalian target of rapamycin (mTORC1), and achieved a complete response with a duration of more than 2 years.

In a separate analysis, researchers sequenced tumors from 96 other individuals with high-grade bladder cancer and identified five TSC1 gene mutations. Tumors were sequenced from 13 patients with bladder cancer who had received everolimus. Results showed that 3 of 4 patients with TSC1 gene mutations experienced some degree of tumor shrinkage after treatment; 8 of 9 patients who did not have the mutation experienced disease progression.

The NCI notes that in “subsequent workshops and discussions, it became obvious that all clinicians have seen a few exceptional responders.”
 

Testing for feasibility

The aim of the current study was to assess the feasibility and potential usefulness of sequencing DNA and RNA from clinical tumor specimens from patients who had experienced unusually profound or durable responses to systemic therapy.

Its main feasibility goal was to identify at least 100 cases involving exceptional responders whose cases could be analyzed in less than 3 years.

An exceptional patient was defined as one who had experienced a complete response to one or more drugs in which complete responses were seen in fewer than 10% of patients who received similar treatment; or a partial response lasting at least 6 months in which such a response is seen in fewer than 10% of patients who receive similar treatment; or a complete or partial response of a duration that is three times the median response duration represented in the literature for the treatment.

Studying exceptional responders presents many challenges, the first being to define what an exceptional response is and what it is not, explained Ivy. “This definition relies on the existence of data that a particular therapy will produce particular responses in groups of patients with similar tumors, as defined by organ of origin,” she said.

Other challenges include obtaining tumor tissue and all the relevant clinical data, such as the number of prior treatments and the patient’s response, as well as any known molecular characteristics (eg, HER2/NEU amplification, estrogen-receptor expression, germline mutations). “We also do not have data on other exposures, such as smoking or chemical exposure,” she said. “In addition, when patients are not on clinical trial, the data are not uniformly obtained ― such as that scans may not be performed at particular intervals.”

Importantly, the molecular tools used to analyze tumors were not available in the past, so many trials did not collect tumor tissue for subsequent research. “Even now, we are learning that there are characteristics beyond DNA and RNA that are potentially important to the ability of a tumor to respond, such as the immune system or epigenetic changes,” she said.

From August 2014 to July 2017, a total of 520 cases were proposed by clinicians as possibly involving exceptional responders, and 222 cases met the criteria.

Analyzable tissue was available for 117 patients. Most of the responders (n = 80, 68.4%) had been treated with combination chemotherapy regimens; 34 patients (29.0%) had received one or more antiangiogenesis agents. In addition, six patients had an exceptional response following treatment with immune checkpoint inhibitors. The final analysis included 109 cases.

One exceptional responder was a woman with metastatic squamous lung cancer that was treated with paclitaxel and carboplatin. The patient achieved a 41-month complete response (expected rate, <10%). Another patient with esophageal adenocarcinoma who was treated with docetaxel and cisplatin experienced a partial response that lasted 128 months (reported median response duration, 24 months). After the patient’s tumor recurred, he experienced for the second time a response to concurrent chemoradiation with the same drug regimen.

Overall, potentially clinically relevant germline mutations were identified in six tumors. Pathogenic BRCA1 or BRCA2 mutations were found in two breast cancer patients, one patient with non–small cell lung cancer, and one patient with rectal cancer. A breast cancer patient had a pathogenic BRCA1 germline mutation, and another had a likely germline mutation in CHEK2. A patient with poorly differentiated lung cancer and a history of breast cancer had a PALB2 mutation.
 

Future steps

Molecular mechanisms are important, but other factors could also play a role in eliciting a response. One is the presence of comorbidities, which was not assessed in the study. Ivy noted that comorbidities could be very important to responses, along with medications that the patient is using for different types of ailments. In addition, the use of complementary and alternative medicines may also have an impact.

“As the field matures, we hope that others will collect these and other characteristics, so that all the data could be used to develop hypotheses about molecular and other factors that can better predict response or resistance,” she said.

The results from this pilot study demonstrated feasibility. Ivy noted that “additional collaboration in similar studies would be welcome, as would methods to use data from various sources to improve our ability to correlate patient characteristics, tumor characteristics and response.

“We envision a larger national and international effort to collect more exceptional responder cases, including more from patients treated with targeted therapies,” she added. “The NCI has been meeting with an interest group that focuses on ER cases in the UK, France, Italy, Canada, and Australia, and this collaborative effort is maturing, albeit slowly.”

The project has been funded in whole or in part with federal funds from the NCI and NIH. Ivy has disclosed no relevant financial relationships. Several coauthors report relationships with industry. The editorialists have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Virtually all oncologists, at one time or another, have treated a patient who defied the odds and achieved an unexpectedly long-lasting response. These “exceptional responders” are patients who experience a unique response to therapies that have largely failed to be effective for others with similar cancers.

Genetic and molecular mechanisms may partly account for these responses and may offer clues about why the treatment works for only a few and not for others. To delve more deeply into that area of research, the National Cancer Institute (NCI) began the Exceptional Responders Initiative (ERI) with the goal of identifying potential biological processes that may be responsible, at least in part, for these unusual responses.

NCI researchers have now successfully completed a pilot study that analyzed tumor specimens from more than 100 cases, and the study has affirmed the feasibility of this approach.

Of these cases, six were identified as involving potentially clinically actionable germline mutations.

The findings were published online ahead of print in the Journal of the National Cancer Institute.

“Clearly, the analysis and validation of these results will prove critical to determining the success of this approach,” write James M. Ford, MD, and Beverly S. Mitchell, MD, both of Stanford University School of Medicine, California, in an accompanying editorial. “Ultimately, prospective studies of tumors from exceptional responders, particularly to novel, genomically-targeted agents, may provide a powerful approach to cancer treatment discoveries.”
 

A special case

Molecular profiling technology, including next-generation sequencing, has significantly changed the landscape of the development of cancer therapies, and clinical trials in early drug development are increasingly selecting patients on the basis of molecular alterations.

The ERI grew out of several meetings held by the NCI in 2013 and 2014. It was built on the ability to profile archived tumor material, explained study author S. Percy Ivy, PhD, associate chief of the Investigational Drug Branch in the Division of Cancer Treatment and Diagnosis of the NCI. “This made it possible to collect cases from participating clinicians from all over the country.

“Published cases included patients treated with a targeted therapy but not treated with knowledge of their tumor’s genomics, who then later turned out to have genomic changes that made their tumor exquisitely sensitive to inhibition of a driving pathway,” she said. “There have been published cases as well as cases in the experience of practicing oncologists that seem to do much better than expected.

“We wondered if we could find molecular reasons why tumors respond not only to targeted therapies but also to standard chemotherapy,” said Percy. “If so, we could refine our choice of therapy to patients who are most likely to respond to it.”’

On its website, the NCI writes that there was a particular case that triggered the interest in going ahead with this initiative. Mutations in the TSC1 and NF2 genes, which result in a loss of gene function, were detected in a patient with metastatic bladder cancer. In a clinical trial, the patient was treated with everolimus (Afinitor, Novartis), an inhibitor of the mammalian target of rapamycin (mTORC1), and achieved a complete response with a duration of more than 2 years.

In a separate analysis, researchers sequenced tumors from 96 other individuals with high-grade bladder cancer and identified five TSC1 gene mutations. Tumors were sequenced from 13 patients with bladder cancer who had received everolimus. Results showed that 3 of 4 patients with TSC1 gene mutations experienced some degree of tumor shrinkage after treatment; 8 of 9 patients who did not have the mutation experienced disease progression.

The NCI notes that in “subsequent workshops and discussions, it became obvious that all clinicians have seen a few exceptional responders.”
 

Testing for feasibility

The aim of the current study was to assess the feasibility and potential usefulness of sequencing DNA and RNA from clinical tumor specimens from patients who had experienced unusually profound or durable responses to systemic therapy.

Its main feasibility goal was to identify at least 100 cases involving exceptional responders whose cases could be analyzed in less than 3 years.

An exceptional patient was defined as one who had experienced a complete response to one or more drugs in which complete responses were seen in fewer than 10% of patients who received similar treatment; or a partial response lasting at least 6 months in which such a response is seen in fewer than 10% of patients who receive similar treatment; or a complete or partial response of a duration that is three times the median response duration represented in the literature for the treatment.

Studying exceptional responders presents many challenges, the first being to define what an exceptional response is and what it is not, explained Ivy. “This definition relies on the existence of data that a particular therapy will produce particular responses in groups of patients with similar tumors, as defined by organ of origin,” she said.

Other challenges include obtaining tumor tissue and all the relevant clinical data, such as the number of prior treatments and the patient’s response, as well as any known molecular characteristics (eg, HER2/NEU amplification, estrogen-receptor expression, germline mutations). “We also do not have data on other exposures, such as smoking or chemical exposure,” she said. “In addition, when patients are not on clinical trial, the data are not uniformly obtained ― such as that scans may not be performed at particular intervals.”

Importantly, the molecular tools used to analyze tumors were not available in the past, so many trials did not collect tumor tissue for subsequent research. “Even now, we are learning that there are characteristics beyond DNA and RNA that are potentially important to the ability of a tumor to respond, such as the immune system or epigenetic changes,” she said.

From August 2014 to July 2017, a total of 520 cases were proposed by clinicians as possibly involving exceptional responders, and 222 cases met the criteria.

Analyzable tissue was available for 117 patients. Most of the responders (n = 80, 68.4%) had been treated with combination chemotherapy regimens; 34 patients (29.0%) had received one or more antiangiogenesis agents. In addition, six patients had an exceptional response following treatment with immune checkpoint inhibitors. The final analysis included 109 cases.

One exceptional responder was a woman with metastatic squamous lung cancer that was treated with paclitaxel and carboplatin. The patient achieved a 41-month complete response (expected rate, <10%). Another patient with esophageal adenocarcinoma who was treated with docetaxel and cisplatin experienced a partial response that lasted 128 months (reported median response duration, 24 months). After the patient’s tumor recurred, he experienced for the second time a response to concurrent chemoradiation with the same drug regimen.

Overall, potentially clinically relevant germline mutations were identified in six tumors. Pathogenic BRCA1 or BRCA2 mutations were found in two breast cancer patients, one patient with non–small cell lung cancer, and one patient with rectal cancer. A breast cancer patient had a pathogenic BRCA1 germline mutation, and another had a likely germline mutation in CHEK2. A patient with poorly differentiated lung cancer and a history of breast cancer had a PALB2 mutation.
 

Future steps

Molecular mechanisms are important, but other factors could also play a role in eliciting a response. One is the presence of comorbidities, which was not assessed in the study. Ivy noted that comorbidities could be very important to responses, along with medications that the patient is using for different types of ailments. In addition, the use of complementary and alternative medicines may also have an impact.

“As the field matures, we hope that others will collect these and other characteristics, so that all the data could be used to develop hypotheses about molecular and other factors that can better predict response or resistance,” she said.

The results from this pilot study demonstrated feasibility. Ivy noted that “additional collaboration in similar studies would be welcome, as would methods to use data from various sources to improve our ability to correlate patient characteristics, tumor characteristics and response.

“We envision a larger national and international effort to collect more exceptional responder cases, including more from patients treated with targeted therapies,” she added. “The NCI has been meeting with an interest group that focuses on ER cases in the UK, France, Italy, Canada, and Australia, and this collaborative effort is maturing, albeit slowly.”

The project has been funded in whole or in part with federal funds from the NCI and NIH. Ivy has disclosed no relevant financial relationships. Several coauthors report relationships with industry. The editorialists have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Virtually all oncologists, at one time or another, have treated a patient who defied the odds and achieved an unexpectedly long-lasting response. These “exceptional responders” are patients who experience a unique response to therapies that have largely failed to be effective for others with similar cancers.

Genetic and molecular mechanisms may partly account for these responses and may offer clues about why the treatment works for only a few and not for others. To delve more deeply into that area of research, the National Cancer Institute (NCI) began the Exceptional Responders Initiative (ERI) with the goal of identifying potential biological processes that may be responsible, at least in part, for these unusual responses.

NCI researchers have now successfully completed a pilot study that analyzed tumor specimens from more than 100 cases, and the study has affirmed the feasibility of this approach.

Of these cases, six were identified as involving potentially clinically actionable germline mutations.

The findings were published online ahead of print in the Journal of the National Cancer Institute.

“Clearly, the analysis and validation of these results will prove critical to determining the success of this approach,” write James M. Ford, MD, and Beverly S. Mitchell, MD, both of Stanford University School of Medicine, California, in an accompanying editorial. “Ultimately, prospective studies of tumors from exceptional responders, particularly to novel, genomically-targeted agents, may provide a powerful approach to cancer treatment discoveries.”
 

A special case

Molecular profiling technology, including next-generation sequencing, has significantly changed the landscape of the development of cancer therapies, and clinical trials in early drug development are increasingly selecting patients on the basis of molecular alterations.

The ERI grew out of several meetings held by the NCI in 2013 and 2014. It was built on the ability to profile archived tumor material, explained study author S. Percy Ivy, PhD, associate chief of the Investigational Drug Branch in the Division of Cancer Treatment and Diagnosis of the NCI. “This made it possible to collect cases from participating clinicians from all over the country.

“Published cases included patients treated with a targeted therapy but not treated with knowledge of their tumor’s genomics, who then later turned out to have genomic changes that made their tumor exquisitely sensitive to inhibition of a driving pathway,” she said. “There have been published cases as well as cases in the experience of practicing oncologists that seem to do much better than expected.

“We wondered if we could find molecular reasons why tumors respond not only to targeted therapies but also to standard chemotherapy,” said Percy. “If so, we could refine our choice of therapy to patients who are most likely to respond to it.”’

On its website, the NCI writes that there was a particular case that triggered the interest in going ahead with this initiative. Mutations in the TSC1 and NF2 genes, which result in a loss of gene function, were detected in a patient with metastatic bladder cancer. In a clinical trial, the patient was treated with everolimus (Afinitor, Novartis), an inhibitor of the mammalian target of rapamycin (mTORC1), and achieved a complete response with a duration of more than 2 years.

In a separate analysis, researchers sequenced tumors from 96 other individuals with high-grade bladder cancer and identified five TSC1 gene mutations. Tumors were sequenced from 13 patients with bladder cancer who had received everolimus. Results showed that 3 of 4 patients with TSC1 gene mutations experienced some degree of tumor shrinkage after treatment; 8 of 9 patients who did not have the mutation experienced disease progression.

The NCI notes that in “subsequent workshops and discussions, it became obvious that all clinicians have seen a few exceptional responders.”
 

Testing for feasibility

The aim of the current study was to assess the feasibility and potential usefulness of sequencing DNA and RNA from clinical tumor specimens from patients who had experienced unusually profound or durable responses to systemic therapy.

Its main feasibility goal was to identify at least 100 cases involving exceptional responders whose cases could be analyzed in less than 3 years.

An exceptional patient was defined as one who had experienced a complete response to one or more drugs in which complete responses were seen in fewer than 10% of patients who received similar treatment; or a partial response lasting at least 6 months in which such a response is seen in fewer than 10% of patients who receive similar treatment; or a complete or partial response of a duration that is three times the median response duration represented in the literature for the treatment.

Studying exceptional responders presents many challenges, the first being to define what an exceptional response is and what it is not, explained Ivy. “This definition relies on the existence of data that a particular therapy will produce particular responses in groups of patients with similar tumors, as defined by organ of origin,” she said.

Other challenges include obtaining tumor tissue and all the relevant clinical data, such as the number of prior treatments and the patient’s response, as well as any known molecular characteristics (eg, HER2/NEU amplification, estrogen-receptor expression, germline mutations). “We also do not have data on other exposures, such as smoking or chemical exposure,” she said. “In addition, when patients are not on clinical trial, the data are not uniformly obtained ― such as that scans may not be performed at particular intervals.”

Importantly, the molecular tools used to analyze tumors were not available in the past, so many trials did not collect tumor tissue for subsequent research. “Even now, we are learning that there are characteristics beyond DNA and RNA that are potentially important to the ability of a tumor to respond, such as the immune system or epigenetic changes,” she said.

From August 2014 to July 2017, a total of 520 cases were proposed by clinicians as possibly involving exceptional responders, and 222 cases met the criteria.

Analyzable tissue was available for 117 patients. Most of the responders (n = 80, 68.4%) had been treated with combination chemotherapy regimens; 34 patients (29.0%) had received one or more antiangiogenesis agents. In addition, six patients had an exceptional response following treatment with immune checkpoint inhibitors. The final analysis included 109 cases.

One exceptional responder was a woman with metastatic squamous lung cancer that was treated with paclitaxel and carboplatin. The patient achieved a 41-month complete response (expected rate, <10%). Another patient with esophageal adenocarcinoma who was treated with docetaxel and cisplatin experienced a partial response that lasted 128 months (reported median response duration, 24 months). After the patient’s tumor recurred, he experienced for the second time a response to concurrent chemoradiation with the same drug regimen.

Overall, potentially clinically relevant germline mutations were identified in six tumors. Pathogenic BRCA1 or BRCA2 mutations were found in two breast cancer patients, one patient with non–small cell lung cancer, and one patient with rectal cancer. A breast cancer patient had a pathogenic BRCA1 germline mutation, and another had a likely germline mutation in CHEK2. A patient with poorly differentiated lung cancer and a history of breast cancer had a PALB2 mutation.
 

Future steps

Molecular mechanisms are important, but other factors could also play a role in eliciting a response. One is the presence of comorbidities, which was not assessed in the study. Ivy noted that comorbidities could be very important to responses, along with medications that the patient is using for different types of ailments. In addition, the use of complementary and alternative medicines may also have an impact.

“As the field matures, we hope that others will collect these and other characteristics, so that all the data could be used to develop hypotheses about molecular and other factors that can better predict response or resistance,” she said.

The results from this pilot study demonstrated feasibility. Ivy noted that “additional collaboration in similar studies would be welcome, as would methods to use data from various sources to improve our ability to correlate patient characteristics, tumor characteristics and response.

“We envision a larger national and international effort to collect more exceptional responder cases, including more from patients treated with targeted therapies,” she added. “The NCI has been meeting with an interest group that focuses on ER cases in the UK, France, Italy, Canada, and Australia, and this collaborative effort is maturing, albeit slowly.”

The project has been funded in whole or in part with federal funds from the NCI and NIH. Ivy has disclosed no relevant financial relationships. Several coauthors report relationships with industry. The editorialists have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

Quitting smoking prior to a lung cancer diagnosis is associated with a survival benefit, even among patients who recently stopped smoking, according to results of a pooled analysis.

Brett Mulcahy/ThinkStock

The overall survival advantage was significant regardless of how long ago patients had last smoked, including among those who quit within 2 years prior to their diagnosis.

These findings create a “teachable moment” for health care providers in scenarios when patients might be more receptive to a stop-smoking message, according to investigator Aline F. Fares, MD, a clinical research fellow at Princess Margaret Cancer Centre in Toronto.

“Our study can be summarized to patients as, ‘it’s never too late to quit,’ ” Dr. Fares said.

She presented results from this study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online May 29-31. The virtual education program will be available Aug. 8-10.
 

Results

Dr. Fares presented data on 35,481 patients with a diagnosis of lung cancer who had been enrolled in 17 studies conducted by the International Lung Cancer Consortium. (Data in the presentation were updated from the abstract.)

At diagnosis, 47.5% of the patients were current smokers, 30% were former smokers, and 22.5% were never smokers.

The risk of death from any cause was cut by 20% among former smokers who quit more than 5 years before their lung cancer diagnosis (P < .001). Patients who quit smoking 2-5 years before diagnosis had a 16% reduction in the risk of death, while those who quit within 2 years of diagnosis had a 12% reduced risk (P < .001 for both comparisons).

The overall survival advantage was evident in this pooled analysis regardless of patient sex, disease stage, histology, or amount of smoking as measured in pack-years, according to Dr. Fares. That said, the overall survival advantage appeared to be even greater among heavier smokers (i.e., greater than 30 pack-years) as compared with lighter smokers.

Lung cancer–specific survival was improved by 15% for patients who quit smoking more than 5 years prior to their diagnosis. For those who had quit more recently, there was a nonsignificant trend toward improvement in this outcome.

Overall survival was higher in never smokers in comparison with current smokers, a finding that was expected based on previous studies, according to Dr. Fares.
 

Implications

These findings could be important to share with individuals who are current smokers at the time of lung cancer screening, according to Maher A. Karam-Hage, MD, medical director of the tobacco treatment program at the University of Texas MD Anderson Cancer Center, Houston.

“The power of this data is that it shows quitting makes a difference, and that it can be more impactful the longer you quit before you get diagnosed,” Dr. Karam-Hage said in an interview.

Negative lung cancer screening results sometimes give individuals the false impression that they are “one of the lucky ones” who won’t get lung cancer and don’t have to quit smoking, according to Dr. Karam-Hage, who is studying the comparative effectiveness of different smoking cessation strategies.

“Now, as part of shared decision making, we can provide people with specific numbers before the scan that [suggest] no matter what the scan comes out with, the earlier they quit, the better off they will be,” he said.

In her presentation, Dr. Fares said that lung cancer screening may be an “interesting time” to address smoking cessation, particularly among patients with a heavier smoking history.

“After a lifetime of smoking, patients often feel it’s too late to quit smoking and that the damage has already been done,” she added.

The International Lung Cancer Consortium studies had multiple supporters. Dr. Fares reported having no disclosures related to the research. One researcher reported relationships with AbbVie, AstraZeneca, MedImmune, Bayer, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche Canada, and Takeda. Dr. Karam-Hage reported having no relevant disclosures.

SOURCE: Fares AF et al. ASCO 2020, Abstract 1512.

This article was updated 5/15/20.

Quitting smoking prior to a lung cancer diagnosis is associated with a survival benefit, even among patients who recently stopped smoking, according to results of a pooled analysis.

Brett Mulcahy/ThinkStock

The overall survival advantage was significant regardless of how long ago patients had last smoked, including among those who quit within 2 years prior to their diagnosis.

These findings create a “teachable moment” for health care providers in scenarios when patients might be more receptive to a stop-smoking message, according to investigator Aline F. Fares, MD, a clinical research fellow at Princess Margaret Cancer Centre in Toronto.

“Our study can be summarized to patients as, ‘it’s never too late to quit,’ ” Dr. Fares said.

She presented results from this study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online May 29-31. The virtual education program will be available Aug. 8-10.
 

Results

Dr. Fares presented data on 35,481 patients with a diagnosis of lung cancer who had been enrolled in 17 studies conducted by the International Lung Cancer Consortium. (Data in the presentation were updated from the abstract.)

At diagnosis, 47.5% of the patients were current smokers, 30% were former smokers, and 22.5% were never smokers.

The risk of death from any cause was cut by 20% among former smokers who quit more than 5 years before their lung cancer diagnosis (P < .001). Patients who quit smoking 2-5 years before diagnosis had a 16% reduction in the risk of death, while those who quit within 2 years of diagnosis had a 12% reduced risk (P < .001 for both comparisons).

The overall survival advantage was evident in this pooled analysis regardless of patient sex, disease stage, histology, or amount of smoking as measured in pack-years, according to Dr. Fares. That said, the overall survival advantage appeared to be even greater among heavier smokers (i.e., greater than 30 pack-years) as compared with lighter smokers.

Lung cancer–specific survival was improved by 15% for patients who quit smoking more than 5 years prior to their diagnosis. For those who had quit more recently, there was a nonsignificant trend toward improvement in this outcome.

Overall survival was higher in never smokers in comparison with current smokers, a finding that was expected based on previous studies, according to Dr. Fares.
 

Implications

These findings could be important to share with individuals who are current smokers at the time of lung cancer screening, according to Maher A. Karam-Hage, MD, medical director of the tobacco treatment program at the University of Texas MD Anderson Cancer Center, Houston.

“The power of this data is that it shows quitting makes a difference, and that it can be more impactful the longer you quit before you get diagnosed,” Dr. Karam-Hage said in an interview.

Negative lung cancer screening results sometimes give individuals the false impression that they are “one of the lucky ones” who won’t get lung cancer and don’t have to quit smoking, according to Dr. Karam-Hage, who is studying the comparative effectiveness of different smoking cessation strategies.

“Now, as part of shared decision making, we can provide people with specific numbers before the scan that [suggest] no matter what the scan comes out with, the earlier they quit, the better off they will be,” he said.

In her presentation, Dr. Fares said that lung cancer screening may be an “interesting time” to address smoking cessation, particularly among patients with a heavier smoking history.

“After a lifetime of smoking, patients often feel it’s too late to quit smoking and that the damage has already been done,” she added.

The International Lung Cancer Consortium studies had multiple supporters. Dr. Fares reported having no disclosures related to the research. One researcher reported relationships with AbbVie, AstraZeneca, MedImmune, Bayer, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche Canada, and Takeda. Dr. Karam-Hage reported having no relevant disclosures.

SOURCE: Fares AF et al. ASCO 2020, Abstract 1512.

This article was updated 5/15/20.

Quitting smoking prior to a lung cancer diagnosis is associated with a survival benefit, even among patients who recently stopped smoking, according to results of a pooled analysis.

Brett Mulcahy/ThinkStock

The overall survival advantage was significant regardless of how long ago patients had last smoked, including among those who quit within 2 years prior to their diagnosis.

These findings create a “teachable moment” for health care providers in scenarios when patients might be more receptive to a stop-smoking message, according to investigator Aline F. Fares, MD, a clinical research fellow at Princess Margaret Cancer Centre in Toronto.

“Our study can be summarized to patients as, ‘it’s never too late to quit,’ ” Dr. Fares said.

She presented results from this study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online May 29-31. The virtual education program will be available Aug. 8-10.
 

Results

Dr. Fares presented data on 35,481 patients with a diagnosis of lung cancer who had been enrolled in 17 studies conducted by the International Lung Cancer Consortium. (Data in the presentation were updated from the abstract.)

At diagnosis, 47.5% of the patients were current smokers, 30% were former smokers, and 22.5% were never smokers.

The risk of death from any cause was cut by 20% among former smokers who quit more than 5 years before their lung cancer diagnosis (P < .001). Patients who quit smoking 2-5 years before diagnosis had a 16% reduction in the risk of death, while those who quit within 2 years of diagnosis had a 12% reduced risk (P < .001 for both comparisons).

The overall survival advantage was evident in this pooled analysis regardless of patient sex, disease stage, histology, or amount of smoking as measured in pack-years, according to Dr. Fares. That said, the overall survival advantage appeared to be even greater among heavier smokers (i.e., greater than 30 pack-years) as compared with lighter smokers.

Lung cancer–specific survival was improved by 15% for patients who quit smoking more than 5 years prior to their diagnosis. For those who had quit more recently, there was a nonsignificant trend toward improvement in this outcome.

Overall survival was higher in never smokers in comparison with current smokers, a finding that was expected based on previous studies, according to Dr. Fares.
 

Implications

These findings could be important to share with individuals who are current smokers at the time of lung cancer screening, according to Maher A. Karam-Hage, MD, medical director of the tobacco treatment program at the University of Texas MD Anderson Cancer Center, Houston.

“The power of this data is that it shows quitting makes a difference, and that it can be more impactful the longer you quit before you get diagnosed,” Dr. Karam-Hage said in an interview.

Negative lung cancer screening results sometimes give individuals the false impression that they are “one of the lucky ones” who won’t get lung cancer and don’t have to quit smoking, according to Dr. Karam-Hage, who is studying the comparative effectiveness of different smoking cessation strategies.

“Now, as part of shared decision making, we can provide people with specific numbers before the scan that [suggest] no matter what the scan comes out with, the earlier they quit, the better off they will be,” he said.

In her presentation, Dr. Fares said that lung cancer screening may be an “interesting time” to address smoking cessation, particularly among patients with a heavier smoking history.

“After a lifetime of smoking, patients often feel it’s too late to quit smoking and that the damage has already been done,” she added.

The International Lung Cancer Consortium studies had multiple supporters. Dr. Fares reported having no disclosures related to the research. One researcher reported relationships with AbbVie, AstraZeneca, MedImmune, Bayer, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche Canada, and Takeda. Dr. Karam-Hage reported having no relevant disclosures.

SOURCE: Fares AF et al. ASCO 2020, Abstract 1512.

This article was updated 5/15/20.

Anxiety and distress related to caring for a cancer patient who lives far away may be alleviated through an intervention that includes video-based coaching sessions with a nurse practitioner or social worker, a randomized study suggests.

AJ_Watt/E+

About 20% of long-distance caregivers had a significant reduction in anxiety and 25% had a significant reduction in distress when they received video coaching sessions, attended oncologist visits via video, and had access to a website specifically designed for their needs.

Adding the caregiver to oncologist office visits made the patients feel better supported and didn’t add a significant amount of time to the encounter, said Sara L. Douglas, PhD, RN, of Case Western Reserve University, Cleveland.

Taken together, these results suggest that fairly simple technologies can be leveraged to help caregivers cope with psychological strains related to supporting a patient who doesn’t live nearby, Dr. Douglas said.

Distance caregivers, defined as those who live an hour or more away from the patient, can experience high rates of distress and anxiety because they lack first-hand information or may have uncertainty about the patient’s current condition, according to Dr. Douglas and colleagues.

“Caregivers’ high rates of anxiety and distress have been found to have a negative impact not only upon their own health but upon their ability to provide high quality care to the patient,” Dr. Douglas said.

With this in mind, she and her colleagues conducted a 4-month study of distance caregivers. Dr. Douglas presented results from the study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online on May 29-31, and the virtual education program will be available Aug. 8-10.
 

Study details

The study enrolled 441 distance caregivers of cancer patients, and Dr. Douglas presented results in 311 of those caregivers. (Data in the presentation differ from the abstract.) The caregivers were, on average, 47 years of age. Most were female (72%), white (67%), the child of the patient (63%), currently employed (81%), and new to the distance caregiver role (89%).

The caregivers were randomized to one of three study arms.

One arm received the full intervention, which consisted of four video-coaching sessions with an advanced practice nurse or social worker, videoconference office visits with the physician and patient, and access to a website with information for cancer distance caregivers. A second arm received no video coaching but had access to the website and participated in video visits with the physician and patient. The third arm, which only received access to the website, served as the study’s control group.
 

Results

Dr. Douglas said that the full intervention had the biggest impact on caregivers’ distress and anxiety.

Among distance caregivers who received the full intervention, 19.2% had a significant reduction in anxiety (P = .03), as measured in online surveys before and after the intervention using the PROMIS Anxiety instrument. Furthermore, 24.8% of these caregivers had a significant reduction in distress (P = .02) from preintervention to post intervention, as measured by the National Comprehensive Cancer Network Distress Thermometer. Overall, distress and anxiety scores decreased in this arm.

Distance caregivers who only had physician-patient video visits and website access had a “moderate” reduction in distress and anxiety, Dr. Douglas said. Among these caregivers, 17.3% had an improvement in anxiety from baseline, and 19.8% had an improvement in distress. Overall, distress scores decreased, but anxiety scores increased slightly in this arm.

In the control arm, 13.1% of caregivers had an improvement in anxiety from baseline, and 18% had an improvement in distress. Overall, both anxiety and distress scores increased in this arm.

“While the full intervention yielded the best results for distance caregivers, we recognize that not all health care systems have the resources to provide individualized coaching sessions to distance caregivers,” Dr. Douglas said. “Therefore, it is worth noting that videoconference office visits alone are found to be of some benefit in improving distress and anxiety in this group of cancer caregivers.”

The study results suggest videoconferencing interventions can improve the emotional well-being of remote caregivers who provide “critical support” for cancer patients, said ASCO President Howard A. “Skip” Burris III, MD.

“As COVID-19 forces separation from loved ones and increases anxiety for people with cancer and their caregivers, providing emotional support virtually is more important than ever,” Dr. Burris said in a news release highlighting the study.

This study was funded by the National Institutes of Health and Case Comprehensive Cancer Center. Dr. Douglas reported having no disclosures. Other researchers involved in the study disclosed relationships with BridgeBio Pharma, Cardinal Health, Apexigen, Roche/Genentech, Seattle Genetics, Tesaro, Array BioPharma, Abbvie, Bristol-Myers Squibb, and Celgene. A full list of Dr. Burris’s financial disclosures is available on the ASCO website.

SOURCE: Douglas SL et al. ASCO 2020, Abstract 12123.

Anxiety and distress related to caring for a cancer patient who lives far away may be alleviated through an intervention that includes video-based coaching sessions with a nurse practitioner or social worker, a randomized study suggests.

AJ_Watt/E+

About 20% of long-distance caregivers had a significant reduction in anxiety and 25% had a significant reduction in distress when they received video coaching sessions, attended oncologist visits via video, and had access to a website specifically designed for their needs.

Adding the caregiver to oncologist office visits made the patients feel better supported and didn’t add a significant amount of time to the encounter, said Sara L. Douglas, PhD, RN, of Case Western Reserve University, Cleveland.

Taken together, these results suggest that fairly simple technologies can be leveraged to help caregivers cope with psychological strains related to supporting a patient who doesn’t live nearby, Dr. Douglas said.

Distance caregivers, defined as those who live an hour or more away from the patient, can experience high rates of distress and anxiety because they lack first-hand information or may have uncertainty about the patient’s current condition, according to Dr. Douglas and colleagues.

“Caregivers’ high rates of anxiety and distress have been found to have a negative impact not only upon their own health but upon their ability to provide high quality care to the patient,” Dr. Douglas said.

With this in mind, she and her colleagues conducted a 4-month study of distance caregivers. Dr. Douglas presented results from the study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online on May 29-31, and the virtual education program will be available Aug. 8-10.
 

Study details

The study enrolled 441 distance caregivers of cancer patients, and Dr. Douglas presented results in 311 of those caregivers. (Data in the presentation differ from the abstract.) The caregivers were, on average, 47 years of age. Most were female (72%), white (67%), the child of the patient (63%), currently employed (81%), and new to the distance caregiver role (89%).

The caregivers were randomized to one of three study arms.

One arm received the full intervention, which consisted of four video-coaching sessions with an advanced practice nurse or social worker, videoconference office visits with the physician and patient, and access to a website with information for cancer distance caregivers. A second arm received no video coaching but had access to the website and participated in video visits with the physician and patient. The third arm, which only received access to the website, served as the study’s control group.
 

Results

Dr. Douglas said that the full intervention had the biggest impact on caregivers’ distress and anxiety.

Among distance caregivers who received the full intervention, 19.2% had a significant reduction in anxiety (P = .03), as measured in online surveys before and after the intervention using the PROMIS Anxiety instrument. Furthermore, 24.8% of these caregivers had a significant reduction in distress (P = .02) from preintervention to post intervention, as measured by the National Comprehensive Cancer Network Distress Thermometer. Overall, distress and anxiety scores decreased in this arm.

Distance caregivers who only had physician-patient video visits and website access had a “moderate” reduction in distress and anxiety, Dr. Douglas said. Among these caregivers, 17.3% had an improvement in anxiety from baseline, and 19.8% had an improvement in distress. Overall, distress scores decreased, but anxiety scores increased slightly in this arm.

In the control arm, 13.1% of caregivers had an improvement in anxiety from baseline, and 18% had an improvement in distress. Overall, both anxiety and distress scores increased in this arm.

“While the full intervention yielded the best results for distance caregivers, we recognize that not all health care systems have the resources to provide individualized coaching sessions to distance caregivers,” Dr. Douglas said. “Therefore, it is worth noting that videoconference office visits alone are found to be of some benefit in improving distress and anxiety in this group of cancer caregivers.”

The study results suggest videoconferencing interventions can improve the emotional well-being of remote caregivers who provide “critical support” for cancer patients, said ASCO President Howard A. “Skip” Burris III, MD.

“As COVID-19 forces separation from loved ones and increases anxiety for people with cancer and their caregivers, providing emotional support virtually is more important than ever,” Dr. Burris said in a news release highlighting the study.

This study was funded by the National Institutes of Health and Case Comprehensive Cancer Center. Dr. Douglas reported having no disclosures. Other researchers involved in the study disclosed relationships with BridgeBio Pharma, Cardinal Health, Apexigen, Roche/Genentech, Seattle Genetics, Tesaro, Array BioPharma, Abbvie, Bristol-Myers Squibb, and Celgene. A full list of Dr. Burris’s financial disclosures is available on the ASCO website.

SOURCE: Douglas SL et al. ASCO 2020, Abstract 12123.

Anxiety and distress related to caring for a cancer patient who lives far away may be alleviated through an intervention that includes video-based coaching sessions with a nurse practitioner or social worker, a randomized study suggests.

AJ_Watt/E+

About 20% of long-distance caregivers had a significant reduction in anxiety and 25% had a significant reduction in distress when they received video coaching sessions, attended oncologist visits via video, and had access to a website specifically designed for their needs.

Adding the caregiver to oncologist office visits made the patients feel better supported and didn’t add a significant amount of time to the encounter, said Sara L. Douglas, PhD, RN, of Case Western Reserve University, Cleveland.

Taken together, these results suggest that fairly simple technologies can be leveraged to help caregivers cope with psychological strains related to supporting a patient who doesn’t live nearby, Dr. Douglas said.

Distance caregivers, defined as those who live an hour or more away from the patient, can experience high rates of distress and anxiety because they lack first-hand information or may have uncertainty about the patient’s current condition, according to Dr. Douglas and colleagues.

“Caregivers’ high rates of anxiety and distress have been found to have a negative impact not only upon their own health but upon their ability to provide high quality care to the patient,” Dr. Douglas said.

With this in mind, she and her colleagues conducted a 4-month study of distance caregivers. Dr. Douglas presented results from the study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online on May 29-31, and the virtual education program will be available Aug. 8-10.
 

Study details

The study enrolled 441 distance caregivers of cancer patients, and Dr. Douglas presented results in 311 of those caregivers. (Data in the presentation differ from the abstract.) The caregivers were, on average, 47 years of age. Most were female (72%), white (67%), the child of the patient (63%), currently employed (81%), and new to the distance caregiver role (89%).

The caregivers were randomized to one of three study arms.

One arm received the full intervention, which consisted of four video-coaching sessions with an advanced practice nurse or social worker, videoconference office visits with the physician and patient, and access to a website with information for cancer distance caregivers. A second arm received no video coaching but had access to the website and participated in video visits with the physician and patient. The third arm, which only received access to the website, served as the study’s control group.
 

Results

Dr. Douglas said that the full intervention had the biggest impact on caregivers’ distress and anxiety.

Among distance caregivers who received the full intervention, 19.2% had a significant reduction in anxiety (P = .03), as measured in online surveys before and after the intervention using the PROMIS Anxiety instrument. Furthermore, 24.8% of these caregivers had a significant reduction in distress (P = .02) from preintervention to post intervention, as measured by the National Comprehensive Cancer Network Distress Thermometer. Overall, distress and anxiety scores decreased in this arm.

Distance caregivers who only had physician-patient video visits and website access had a “moderate” reduction in distress and anxiety, Dr. Douglas said. Among these caregivers, 17.3% had an improvement in anxiety from baseline, and 19.8% had an improvement in distress. Overall, distress scores decreased, but anxiety scores increased slightly in this arm.

In the control arm, 13.1% of caregivers had an improvement in anxiety from baseline, and 18% had an improvement in distress. Overall, both anxiety and distress scores increased in this arm.

“While the full intervention yielded the best results for distance caregivers, we recognize that not all health care systems have the resources to provide individualized coaching sessions to distance caregivers,” Dr. Douglas said. “Therefore, it is worth noting that videoconference office visits alone are found to be of some benefit in improving distress and anxiety in this group of cancer caregivers.”

The study results suggest videoconferencing interventions can improve the emotional well-being of remote caregivers who provide “critical support” for cancer patients, said ASCO President Howard A. “Skip” Burris III, MD.

“As COVID-19 forces separation from loved ones and increases anxiety for people with cancer and their caregivers, providing emotional support virtually is more important than ever,” Dr. Burris said in a news release highlighting the study.

This study was funded by the National Institutes of Health and Case Comprehensive Cancer Center. Dr. Douglas reported having no disclosures. Other researchers involved in the study disclosed relationships with BridgeBio Pharma, Cardinal Health, Apexigen, Roche/Genentech, Seattle Genetics, Tesaro, Array BioPharma, Abbvie, Bristol-Myers Squibb, and Celgene. A full list of Dr. Burris’s financial disclosures is available on the ASCO website.

SOURCE: Douglas SL et al. ASCO 2020, Abstract 12123.

Minimal residual disease (MRD) surveillance after surgery can detect relapse in advance of imaging in patients with early-stage non–small cell lung cancer (NSCLC), according to findings from the TRACERx study.

The findings pave the way for clinical trials of MRD-driven treatment escalation, Chris Abbosh, MD, of University College London, reported during a presentation at the AACR virtual meeting I. Data in the presentation were updated from the abstract.

Dr. Abbosh and colleagues used phylogenetic circulating tumor DNA (ctDNA) profiling to assess MRD and predict relapse in patients from the TRACERx study who underwent surgery for stage I-III NSCLC.

“The approach we take is technically termed a ‘tumor-informed, personalized cell-free DNA-enrichment approach,’” Dr. Abbosh explained. “We take out the primary tumor from the patient, we multiregion sample that tumor, and submit each region for deep whole-exome sequencing.”

The researchers prioritize variants for MRD tracking based on clonality/subclonality, high copy number status, and low background sequencing noise. The researchers then construct an anchored-multiplex PCR panel against the positions of interest, which is applied to cell-free DNA in the pre- and postoperative setting.

“We’ve developed an MRD caller to go alongside this chemistry,” Dr. Abbosh said. “The main premise behind the MRD caller is that it can calculate intralibrary error rates to inform the MRD pool.”
 

Sensitivity and specificity

To validate their approach, Dr. Abbosh and colleagues tested the assay with low DNA input (5 ng, 10 ng) and high DNA input (30 ng, 60 ng). They found the assay to be more sensitive with higher DNA input, and variant fractions were detected down to 0.003%.

The researchers also assessed how sensitivity and specificity scale with an increasing number of variants – 50, 100, or 200 variants. When tracking 200 variants, the assay was powered to detect lower ctDNA fractions than when tracking 50 variants. On the other hand, specificity was higher with 50 variants (99.8%) than with 200 variants (99.4%).

Next, Dr. Abbosh and colleagues analyzed postoperative cell-free DNA collected at 271 time points from 37 NSCLC patients who did not relapse. This included 11 patients who developed proven second primary malignancies.

Of the 271 time points when MRD negativity was expected, MRD was not detected at 269 time points, which translates to 99.3% specificity for the assay.
 

Shedding, relapse, and disease-free survival

Dr. Abbosh and colleagues also found that non-adenocarcinoma histology is associated with preoperative ctDNA shedding in NSCLC. The researchers analyzed 88 early-stage preoperative samples from NSCLC patients. ctDNA was detected preoperatively in 49% of lung adenocarcinomas and 100% of lung squamous cell carcinomas.

“This finding is important when it comes to interpreting our non–small cell lung cancer relapse data from 53 TRACERx patients,” Dr. Abbosh said.

Of the 53 patients who relapsed, 42 had ctDNA detected prior to surgery and were thus considered shedders, while 11 were nonshedders. ctDNA was detectable at or before relapse in 91% (38/42) of shedders and 64% (7/11) of nonshedders.

The median time from ctDNA detection to clinical relapse was 164 days in shedders and 22 days in nonshedders. The median disease-free survival was 362 days and 640 days, respectively.

“So what these data suggest is that preoperative ctDNA detection status will be a proxy of the potential utility of ctDNA as an MRD biomarker in a clinical setting,” Dr. Abbosh explained.

Standard-of-care imaging findings in the 53 patients who relapsed further demonstrated the utility of ctDNA in this setting, Dr. Abbosh said.

All scans were divided into three categories: those showing unequivocal relapse, those with a new equivocal change (relapse, inflammation, or a nonspecific finding), and those with no evidence of relapse. Each was further categorized by preimaging MRD status.

Relapse occurred in 9 of 10 patients who were MRD positive but had a scan showing no evidence of relapse. Relapse occurred in 15 of 16 patients who were MRD positive and had scans showing new equivocal changes.

Patients with unequivocal evidence of relapse who were MRD negative at or before the scan were more likely to have a second primary cancer than to have NSCLC relapse (52% vs. 48%), which is a reflection of the specificity of the MRD assay to the primary tumor, Dr. Abbosh said.
 

Implications of the findings

The researchers’ findings are important because establishing an MRD-driven approach to treating early-stage NSCLC would facilitate escalation of standard-of-care treatment only for those patients at high risk for relapse, thereby overcoming a key challenge in conventional adjuvant drug-trial design, Dr. Abbosh said.

“If we take a patient population with high-risk early-stage disease who have undergone potentially curative resection of their cancer and we offer these patients adjuvant chemotherapy or adjuvant chemoradiation therapy, then we can improve 5-year survival outcomes in this population,” Dr. Abbosh said. “This is striking because, if we give the same treatment in the metastatic setting, we only see a progression-free survival benefit of a short number of months.”

This suggests a potential “vulnerability of low-burden residual cancer to systemic treatment following surgery,” he added. “So if we want to improve outcomes further in non–small cell lung cancer, we really need to focus on innovation in the early-stage space.”

Dr. Abbosh said he and colleagues demonstrated that “personalized cell-free DNA enrichment can detect low-frequency variant DNA in an accurate manner.

“We’ve shown that preoperative ctDNA shedding is associated with utility of ctDNA as an MRD biomarker and that MRD surveillance can lead to detection of relapse in advance of standard-of-care-imaging,” he said. “We feel that the field is now ready for MRD-driven adjuvant trials.”
 

Questions to be answered

Invited discussant Corey J. Langer, MD, of Penn Medicine in Philadelphia, outlined “fundamental questions” raised by the findings.

“We need more information on the staging and demographics of those who were MRD positive versus MRD negative,” he said.

Dr. Langer also asked about the findings for shedders versus nonshedders.

“Does this mean nonshedders fare better? This needs to addressed formally,” he said.

Another question is whether the assay “simply enables us to detect relapse sooner and increase anxiety,” or if the trajectory and outcomes in those who prove MRD positive ahead of radiographic manifestations can actually be altered.

A study comparing standard observation with early immunotherapy or chemoimmunotherapy in patients with MRD-positive radiographically occult relapse or progression – using progression-free and overall survival, along with time without symptoms of disease or relapse – would be useful, Dr. Langer said.

“A hazard ratio of 0.8 or less would be meaningful,” he added. “In this regard, there are trials looking at enhanced adjuvant treatment both in colorectal and breast cancer, and trials planned in advanced non–small cell [lung cancer].”

Dr. Langer also said it would be interesting to know if the assay can be used as an adjunct to diagnosis in frailer patients with inaccessible tumors or equivocal biopsy results or to avoid invasive procedures in patients who are stereotactic radiation candidates.

“The jury is still out on this,” he said.

TRACERx is funded by University College London in collaboration with Cancer Research UK. Dr. Abbosh disclosed relationships with AstraZeneca, Novartis, Roche Diagnostics, Bristol Myers Squibb, Achilles Therapeutics, and Archer Diagnostics. Dr. Langer reported grant/research support and/or scientific advisory work for multiple companies.

sworcester@mdedge.com

SOURCE: Abbosh C et al. AACR 2020, Abstract CT023.

Minimal residual disease (MRD) surveillance after surgery can detect relapse in advance of imaging in patients with early-stage non–small cell lung cancer (NSCLC), according to findings from the TRACERx study.

The findings pave the way for clinical trials of MRD-driven treatment escalation, Chris Abbosh, MD, of University College London, reported during a presentation at the AACR virtual meeting I. Data in the presentation were updated from the abstract.

Dr. Abbosh and colleagues used phylogenetic circulating tumor DNA (ctDNA) profiling to assess MRD and predict relapse in patients from the TRACERx study who underwent surgery for stage I-III NSCLC.

“The approach we take is technically termed a ‘tumor-informed, personalized cell-free DNA-enrichment approach,’” Dr. Abbosh explained. “We take out the primary tumor from the patient, we multiregion sample that tumor, and submit each region for deep whole-exome sequencing.”

The researchers prioritize variants for MRD tracking based on clonality/subclonality, high copy number status, and low background sequencing noise. The researchers then construct an anchored-multiplex PCR panel against the positions of interest, which is applied to cell-free DNA in the pre- and postoperative setting.

“We’ve developed an MRD caller to go alongside this chemistry,” Dr. Abbosh said. “The main premise behind the MRD caller is that it can calculate intralibrary error rates to inform the MRD pool.”
 

Sensitivity and specificity

To validate their approach, Dr. Abbosh and colleagues tested the assay with low DNA input (5 ng, 10 ng) and high DNA input (30 ng, 60 ng). They found the assay to be more sensitive with higher DNA input, and variant fractions were detected down to 0.003%.

The researchers also assessed how sensitivity and specificity scale with an increasing number of variants – 50, 100, or 200 variants. When tracking 200 variants, the assay was powered to detect lower ctDNA fractions than when tracking 50 variants. On the other hand, specificity was higher with 50 variants (99.8%) than with 200 variants (99.4%).

Next, Dr. Abbosh and colleagues analyzed postoperative cell-free DNA collected at 271 time points from 37 NSCLC patients who did not relapse. This included 11 patients who developed proven second primary malignancies.

Of the 271 time points when MRD negativity was expected, MRD was not detected at 269 time points, which translates to 99.3% specificity for the assay.
 

Shedding, relapse, and disease-free survival

Dr. Abbosh and colleagues also found that non-adenocarcinoma histology is associated with preoperative ctDNA shedding in NSCLC. The researchers analyzed 88 early-stage preoperative samples from NSCLC patients. ctDNA was detected preoperatively in 49% of lung adenocarcinomas and 100% of lung squamous cell carcinomas.

“This finding is important when it comes to interpreting our non–small cell lung cancer relapse data from 53 TRACERx patients,” Dr. Abbosh said.

Of the 53 patients who relapsed, 42 had ctDNA detected prior to surgery and were thus considered shedders, while 11 were nonshedders. ctDNA was detectable at or before relapse in 91% (38/42) of shedders and 64% (7/11) of nonshedders.

The median time from ctDNA detection to clinical relapse was 164 days in shedders and 22 days in nonshedders. The median disease-free survival was 362 days and 640 days, respectively.

“So what these data suggest is that preoperative ctDNA detection status will be a proxy of the potential utility of ctDNA as an MRD biomarker in a clinical setting,” Dr. Abbosh explained.

Standard-of-care imaging findings in the 53 patients who relapsed further demonstrated the utility of ctDNA in this setting, Dr. Abbosh said.

All scans were divided into three categories: those showing unequivocal relapse, those with a new equivocal change (relapse, inflammation, or a nonspecific finding), and those with no evidence of relapse. Each was further categorized by preimaging MRD status.

Relapse occurred in 9 of 10 patients who were MRD positive but had a scan showing no evidence of relapse. Relapse occurred in 15 of 16 patients who were MRD positive and had scans showing new equivocal changes.

Patients with unequivocal evidence of relapse who were MRD negative at or before the scan were more likely to have a second primary cancer than to have NSCLC relapse (52% vs. 48%), which is a reflection of the specificity of the MRD assay to the primary tumor, Dr. Abbosh said.
 

Implications of the findings

The researchers’ findings are important because establishing an MRD-driven approach to treating early-stage NSCLC would facilitate escalation of standard-of-care treatment only for those patients at high risk for relapse, thereby overcoming a key challenge in conventional adjuvant drug-trial design, Dr. Abbosh said.

“If we take a patient population with high-risk early-stage disease who have undergone potentially curative resection of their cancer and we offer these patients adjuvant chemotherapy or adjuvant chemoradiation therapy, then we can improve 5-year survival outcomes in this population,” Dr. Abbosh said. “This is striking because, if we give the same treatment in the metastatic setting, we only see a progression-free survival benefit of a short number of months.”

This suggests a potential “vulnerability of low-burden residual cancer to systemic treatment following surgery,” he added. “So if we want to improve outcomes further in non–small cell lung cancer, we really need to focus on innovation in the early-stage space.”

Dr. Abbosh said he and colleagues demonstrated that “personalized cell-free DNA enrichment can detect low-frequency variant DNA in an accurate manner.

“We’ve shown that preoperative ctDNA shedding is associated with utility of ctDNA as an MRD biomarker and that MRD surveillance can lead to detection of relapse in advance of standard-of-care-imaging,” he said. “We feel that the field is now ready for MRD-driven adjuvant trials.”
 

Questions to be answered

Invited discussant Corey J. Langer, MD, of Penn Medicine in Philadelphia, outlined “fundamental questions” raised by the findings.

“We need more information on the staging and demographics of those who were MRD positive versus MRD negative,” he said.

Dr. Langer also asked about the findings for shedders versus nonshedders.

“Does this mean nonshedders fare better? This needs to addressed formally,” he said.

Another question is whether the assay “simply enables us to detect relapse sooner and increase anxiety,” or if the trajectory and outcomes in those who prove MRD positive ahead of radiographic manifestations can actually be altered.

A study comparing standard observation with early immunotherapy or chemoimmunotherapy in patients with MRD-positive radiographically occult relapse or progression – using progression-free and overall survival, along with time without symptoms of disease or relapse – would be useful, Dr. Langer said.

“A hazard ratio of 0.8 or less would be meaningful,” he added. “In this regard, there are trials looking at enhanced adjuvant treatment both in colorectal and breast cancer, and trials planned in advanced non–small cell [lung cancer].”

Dr. Langer also said it would be interesting to know if the assay can be used as an adjunct to diagnosis in frailer patients with inaccessible tumors or equivocal biopsy results or to avoid invasive procedures in patients who are stereotactic radiation candidates.

“The jury is still out on this,” he said.

TRACERx is funded by University College London in collaboration with Cancer Research UK. Dr. Abbosh disclosed relationships with AstraZeneca, Novartis, Roche Diagnostics, Bristol Myers Squibb, Achilles Therapeutics, and Archer Diagnostics. Dr. Langer reported grant/research support and/or scientific advisory work for multiple companies.

sworcester@mdedge.com

SOURCE: Abbosh C et al. AACR 2020, Abstract CT023.

Minimal residual disease (MRD) surveillance after surgery can detect relapse in advance of imaging in patients with early-stage non–small cell lung cancer (NSCLC), according to findings from the TRACERx study.

The findings pave the way for clinical trials of MRD-driven treatment escalation, Chris Abbosh, MD, of University College London, reported during a presentation at the AACR virtual meeting I. Data in the presentation were updated from the abstract.

Dr. Abbosh and colleagues used phylogenetic circulating tumor DNA (ctDNA) profiling to assess MRD and predict relapse in patients from the TRACERx study who underwent surgery for stage I-III NSCLC.

“The approach we take is technically termed a ‘tumor-informed, personalized cell-free DNA-enrichment approach,’” Dr. Abbosh explained. “We take out the primary tumor from the patient, we multiregion sample that tumor, and submit each region for deep whole-exome sequencing.”

The researchers prioritize variants for MRD tracking based on clonality/subclonality, high copy number status, and low background sequencing noise. The researchers then construct an anchored-multiplex PCR panel against the positions of interest, which is applied to cell-free DNA in the pre- and postoperative setting.

“We’ve developed an MRD caller to go alongside this chemistry,” Dr. Abbosh said. “The main premise behind the MRD caller is that it can calculate intralibrary error rates to inform the MRD pool.”
 

Sensitivity and specificity

To validate their approach, Dr. Abbosh and colleagues tested the assay with low DNA input (5 ng, 10 ng) and high DNA input (30 ng, 60 ng). They found the assay to be more sensitive with higher DNA input, and variant fractions were detected down to 0.003%.

The researchers also assessed how sensitivity and specificity scale with an increasing number of variants – 50, 100, or 200 variants. When tracking 200 variants, the assay was powered to detect lower ctDNA fractions than when tracking 50 variants. On the other hand, specificity was higher with 50 variants (99.8%) than with 200 variants (99.4%).

Next, Dr. Abbosh and colleagues analyzed postoperative cell-free DNA collected at 271 time points from 37 NSCLC patients who did not relapse. This included 11 patients who developed proven second primary malignancies.

Of the 271 time points when MRD negativity was expected, MRD was not detected at 269 time points, which translates to 99.3% specificity for the assay.
 

Shedding, relapse, and disease-free survival

Dr. Abbosh and colleagues also found that non-adenocarcinoma histology is associated with preoperative ctDNA shedding in NSCLC. The researchers analyzed 88 early-stage preoperative samples from NSCLC patients. ctDNA was detected preoperatively in 49% of lung adenocarcinomas and 100% of lung squamous cell carcinomas.

“This finding is important when it comes to interpreting our non–small cell lung cancer relapse data from 53 TRACERx patients,” Dr. Abbosh said.

Of the 53 patients who relapsed, 42 had ctDNA detected prior to surgery and were thus considered shedders, while 11 were nonshedders. ctDNA was detectable at or before relapse in 91% (38/42) of shedders and 64% (7/11) of nonshedders.

The median time from ctDNA detection to clinical relapse was 164 days in shedders and 22 days in nonshedders. The median disease-free survival was 362 days and 640 days, respectively.

“So what these data suggest is that preoperative ctDNA detection status will be a proxy of the potential utility of ctDNA as an MRD biomarker in a clinical setting,” Dr. Abbosh explained.

Standard-of-care imaging findings in the 53 patients who relapsed further demonstrated the utility of ctDNA in this setting, Dr. Abbosh said.

All scans were divided into three categories: those showing unequivocal relapse, those with a new equivocal change (relapse, inflammation, or a nonspecific finding), and those with no evidence of relapse. Each was further categorized by preimaging MRD status.

Relapse occurred in 9 of 10 patients who were MRD positive but had a scan showing no evidence of relapse. Relapse occurred in 15 of 16 patients who were MRD positive and had scans showing new equivocal changes.

Patients with unequivocal evidence of relapse who were MRD negative at or before the scan were more likely to have a second primary cancer than to have NSCLC relapse (52% vs. 48%), which is a reflection of the specificity of the MRD assay to the primary tumor, Dr. Abbosh said.
 

Implications of the findings

The researchers’ findings are important because establishing an MRD-driven approach to treating early-stage NSCLC would facilitate escalation of standard-of-care treatment only for those patients at high risk for relapse, thereby overcoming a key challenge in conventional adjuvant drug-trial design, Dr. Abbosh said.

“If we take a patient population with high-risk early-stage disease who have undergone potentially curative resection of their cancer and we offer these patients adjuvant chemotherapy or adjuvant chemoradiation therapy, then we can improve 5-year survival outcomes in this population,” Dr. Abbosh said. “This is striking because, if we give the same treatment in the metastatic setting, we only see a progression-free survival benefit of a short number of months.”

This suggests a potential “vulnerability of low-burden residual cancer to systemic treatment following surgery,” he added. “So if we want to improve outcomes further in non–small cell lung cancer, we really need to focus on innovation in the early-stage space.”

Dr. Abbosh said he and colleagues demonstrated that “personalized cell-free DNA enrichment can detect low-frequency variant DNA in an accurate manner.

“We’ve shown that preoperative ctDNA shedding is associated with utility of ctDNA as an MRD biomarker and that MRD surveillance can lead to detection of relapse in advance of standard-of-care-imaging,” he said. “We feel that the field is now ready for MRD-driven adjuvant trials.”
 

Questions to be answered

Invited discussant Corey J. Langer, MD, of Penn Medicine in Philadelphia, outlined “fundamental questions” raised by the findings.

“We need more information on the staging and demographics of those who were MRD positive versus MRD negative,” he said.

Dr. Langer also asked about the findings for shedders versus nonshedders.

“Does this mean nonshedders fare better? This needs to addressed formally,” he said.

Another question is whether the assay “simply enables us to detect relapse sooner and increase anxiety,” or if the trajectory and outcomes in those who prove MRD positive ahead of radiographic manifestations can actually be altered.

A study comparing standard observation with early immunotherapy or chemoimmunotherapy in patients with MRD-positive radiographically occult relapse or progression – using progression-free and overall survival, along with time without symptoms of disease or relapse – would be useful, Dr. Langer said.

“A hazard ratio of 0.8 or less would be meaningful,” he added. “In this regard, there are trials looking at enhanced adjuvant treatment both in colorectal and breast cancer, and trials planned in advanced non–small cell [lung cancer].”

Dr. Langer also said it would be interesting to know if the assay can be used as an adjunct to diagnosis in frailer patients with inaccessible tumors or equivocal biopsy results or to avoid invasive procedures in patients who are stereotactic radiation candidates.

“The jury is still out on this,” he said.

TRACERx is funded by University College London in collaboration with Cancer Research UK. Dr. Abbosh disclosed relationships with AstraZeneca, Novartis, Roche Diagnostics, Bristol Myers Squibb, Achilles Therapeutics, and Archer Diagnostics. Dr. Langer reported grant/research support and/or scientific advisory work for multiple companies.

sworcester@mdedge.com

SOURCE: Abbosh C et al. AACR 2020, Abstract CT023.

Traditionally at this time of year, everyone working in cancer turns their attention toward Chicago, and 40,000 or so travel to the city for the annual meeting of the American Society of Clinical Oncology (ASCO).

Not this year.

The McCormick Place convention center has been converted to a field hospital to cope with the ongoing COVID-19 pandemic. The cavernous meeting halls have been filled with makeshift wards with 750 acute care beds, as shown in a tweet from Toni Choueiri, MD, chief of genitourinary oncology at the Dana Farber Cancer Center in Boston.

But the annual meeting is still going ahead, having been transferred online.

“We have to remember that even though there’s a pandemic going on and people are dying every day from coronavirus, people are still dying every day from cancer,” Richard Schilsky, MD, PhD, chief medical officer at ASCO, told Medscape Medical News.

“This pandemic will end, but cancer will continue, and we need to be able to continue to get the most cutting edge scientific results out there to our members and our constituents so they can act on those results on behalf of their patients,” he said.

The ASCO Virtual Scientific Program will take place over the weekend of May 30-31.

“We’re certainly hoping that we’re going to deliver a program that features all of the most important science that would have been presented in person in Chicago,” Schilsky commented in an interview.

Most of the presentations will be prerecorded and then streamed, which “we hope will mitigate any of the technical glitches that could come from trying to do a live broadcast of the meeting,” he said.

There will be 250 oral and 2500 poster presentations in 24 disease-based and specialty tracks.

The majority of the abstracts will be released online on May 13. The majority of the on-demand content will be released on May 29. Some of the abstracts will be highlighted at ASCO press briefings and released on those two dates.

But some of the material will be made available only on the weekend of the meeting. The opening session, plenaries featuring late-breaking abstracts, special highlights sessions, and other clinical science symposia will be broadcast on Saturday, May 30, and Sunday, May 31 (the schedule for the weekend program is available on the ASCO meeting website).

Among the plenary presentations are some clinical results that are likely to change practice immediately, Schilsky predicted. These include data to be presented in the following abstracts:

• Abstract LBA4 on the KEYNOTE-177 study comparing immunotherapy using pembrolizumab (Keytruda, Merck & Co) with chemotherapy in patients with metastatic colorectal cancer whose tumors show microsatellite instability or mismatch repair deficiency;
• Abstract LBA5 on the ADAURA study exploring osimertinib (Tagrisso, AstraZeneca) as adjuvant therapy after complete tumor reseaction in patients with early-stage non–small cell lung cancer whose tumors are EGFR mutation positive;
• Abstract LBA1 on the JAVELIN Bladder 100 study exploring maintenance avelumab (Bavencio, Merck and Pfizer) with best supportive care after platinum-based first-line chemotherapy in patients with advanced urothelial carcinoma.

However, some of the material that would have been part of the annual meeting, which includes mostly educational sessions and invited talks, has been moved to another event, the ASCO Educational Program, to be held in August 2020.

“So I suppose, in the grand scheme of things, the meeting is going to be compressed a little bit,” Schilsky commented. “Obviously, we can’t deliver all the interactions that happen in the hallways and everywhere else at the meeting that really gives so much energy to the meeting, but, at this moment in our history, probably getting the science out there is what’s most important.”
 

Virtual exhibition hall

There will also be a virtual exhibition hall, which will open on May 29.

“Just as there is a typical exhibit hall in the convention center,” Schilsky commented, most of the companies that were planning to be in Chicago have “now transitioned to creating a virtual booth that people who are participating in the virtual meeting can visit.

“I don’t know exactly how each company is going to use their time and their virtual space, and that’s part of the whole learning process here to see how this whole experiment is going to work out,” he added.

Unlike some of the other conferences that have gone virtual, in which access has been made available to everyone for free, registration is still required for the ASCO meeting. But the society notes that the registration fee has been discounted for nonmembers and has been waived for ASCO members. Also, the fee covers both the Virtual Scientific Program in May and the ASCO Educational Program in August.

Registrants will have access to video and slide presentations, as well as discussant commentaries, for 180 days.

The article first appeared on Medscape.com.

Traditionally at this time of year, everyone working in cancer turns their attention toward Chicago, and 40,000 or so travel to the city for the annual meeting of the American Society of Clinical Oncology (ASCO).

Not this year.

The McCormick Place convention center has been converted to a field hospital to cope with the ongoing COVID-19 pandemic. The cavernous meeting halls have been filled with makeshift wards with 750 acute care beds, as shown in a tweet from Toni Choueiri, MD, chief of genitourinary oncology at the Dana Farber Cancer Center in Boston.

But the annual meeting is still going ahead, having been transferred online.

“We have to remember that even though there’s a pandemic going on and people are dying every day from coronavirus, people are still dying every day from cancer,” Richard Schilsky, MD, PhD, chief medical officer at ASCO, told Medscape Medical News.

“This pandemic will end, but cancer will continue, and we need to be able to continue to get the most cutting edge scientific results out there to our members and our constituents so they can act on those results on behalf of their patients,” he said.

The ASCO Virtual Scientific Program will take place over the weekend of May 30-31.

“We’re certainly hoping that we’re going to deliver a program that features all of the most important science that would have been presented in person in Chicago,” Schilsky commented in an interview.

Most of the presentations will be prerecorded and then streamed, which “we hope will mitigate any of the technical glitches that could come from trying to do a live broadcast of the meeting,” he said.

There will be 250 oral and 2500 poster presentations in 24 disease-based and specialty tracks.

The majority of the abstracts will be released online on May 13. The majority of the on-demand content will be released on May 29. Some of the abstracts will be highlighted at ASCO press briefings and released on those two dates.

But some of the material will be made available only on the weekend of the meeting. The opening session, plenaries featuring late-breaking abstracts, special highlights sessions, and other clinical science symposia will be broadcast on Saturday, May 30, and Sunday, May 31 (the schedule for the weekend program is available on the ASCO meeting website).

Among the plenary presentations are some clinical results that are likely to change practice immediately, Schilsky predicted. These include data to be presented in the following abstracts:

• Abstract LBA4 on the KEYNOTE-177 study comparing immunotherapy using pembrolizumab (Keytruda, Merck & Co) with chemotherapy in patients with metastatic colorectal cancer whose tumors show microsatellite instability or mismatch repair deficiency;
• Abstract LBA5 on the ADAURA study exploring osimertinib (Tagrisso, AstraZeneca) as adjuvant therapy after complete tumor reseaction in patients with early-stage non–small cell lung cancer whose tumors are EGFR mutation positive;
• Abstract LBA1 on the JAVELIN Bladder 100 study exploring maintenance avelumab (Bavencio, Merck and Pfizer) with best supportive care after platinum-based first-line chemotherapy in patients with advanced urothelial carcinoma.

However, some of the material that would have been part of the annual meeting, which includes mostly educational sessions and invited talks, has been moved to another event, the ASCO Educational Program, to be held in August 2020.

“So I suppose, in the grand scheme of things, the meeting is going to be compressed a little bit,” Schilsky commented. “Obviously, we can’t deliver all the interactions that happen in the hallways and everywhere else at the meeting that really gives so much energy to the meeting, but, at this moment in our history, probably getting the science out there is what’s most important.”
 

Virtual exhibition hall

There will also be a virtual exhibition hall, which will open on May 29.

“Just as there is a typical exhibit hall in the convention center,” Schilsky commented, most of the companies that were planning to be in Chicago have “now transitioned to creating a virtual booth that people who are participating in the virtual meeting can visit.

“I don’t know exactly how each company is going to use their time and their virtual space, and that’s part of the whole learning process here to see how this whole experiment is going to work out,” he added.

Unlike some of the other conferences that have gone virtual, in which access has been made available to everyone for free, registration is still required for the ASCO meeting. But the society notes that the registration fee has been discounted for nonmembers and has been waived for ASCO members. Also, the fee covers both the Virtual Scientific Program in May and the ASCO Educational Program in August.

Registrants will have access to video and slide presentations, as well as discussant commentaries, for 180 days.

The article first appeared on Medscape.com.

Traditionally at this time of year, everyone working in cancer turns their attention toward Chicago, and 40,000 or so travel to the city for the annual meeting of the American Society of Clinical Oncology (ASCO).

Not this year.

The McCormick Place convention center has been converted to a field hospital to cope with the ongoing COVID-19 pandemic. The cavernous meeting halls have been filled with makeshift wards with 750 acute care beds, as shown in a tweet from Toni Choueiri, MD, chief of genitourinary oncology at the Dana Farber Cancer Center in Boston.

But the annual meeting is still going ahead, having been transferred online.

“We have to remember that even though there’s a pandemic going on and people are dying every day from coronavirus, people are still dying every day from cancer,” Richard Schilsky, MD, PhD, chief medical officer at ASCO, told Medscape Medical News.

“This pandemic will end, but cancer will continue, and we need to be able to continue to get the most cutting edge scientific results out there to our members and our constituents so they can act on those results on behalf of their patients,” he said.

The ASCO Virtual Scientific Program will take place over the weekend of May 30-31.

“We’re certainly hoping that we’re going to deliver a program that features all of the most important science that would have been presented in person in Chicago,” Schilsky commented in an interview.

Most of the presentations will be prerecorded and then streamed, which “we hope will mitigate any of the technical glitches that could come from trying to do a live broadcast of the meeting,” he said.

There will be 250 oral and 2500 poster presentations in 24 disease-based and specialty tracks.

The majority of the abstracts will be released online on May 13. The majority of the on-demand content will be released on May 29. Some of the abstracts will be highlighted at ASCO press briefings and released on those two dates.

But some of the material will be made available only on the weekend of the meeting. The opening session, plenaries featuring late-breaking abstracts, special highlights sessions, and other clinical science symposia will be broadcast on Saturday, May 30, and Sunday, May 31 (the schedule for the weekend program is available on the ASCO meeting website).

Among the plenary presentations are some clinical results that are likely to change practice immediately, Schilsky predicted. These include data to be presented in the following abstracts:

• Abstract LBA4 on the KEYNOTE-177 study comparing immunotherapy using pembrolizumab (Keytruda, Merck & Co) with chemotherapy in patients with metastatic colorectal cancer whose tumors show microsatellite instability or mismatch repair deficiency;
• Abstract LBA5 on the ADAURA study exploring osimertinib (Tagrisso, AstraZeneca) as adjuvant therapy after complete tumor reseaction in patients with early-stage non–small cell lung cancer whose tumors are EGFR mutation positive;
• Abstract LBA1 on the JAVELIN Bladder 100 study exploring maintenance avelumab (Bavencio, Merck and Pfizer) with best supportive care after platinum-based first-line chemotherapy in patients with advanced urothelial carcinoma.

However, some of the material that would have been part of the annual meeting, which includes mostly educational sessions and invited talks, has been moved to another event, the ASCO Educational Program, to be held in August 2020.

“So I suppose, in the grand scheme of things, the meeting is going to be compressed a little bit,” Schilsky commented. “Obviously, we can’t deliver all the interactions that happen in the hallways and everywhere else at the meeting that really gives so much energy to the meeting, but, at this moment in our history, probably getting the science out there is what’s most important.”
 

Virtual exhibition hall

There will also be a virtual exhibition hall, which will open on May 29.

“Just as there is a typical exhibit hall in the convention center,” Schilsky commented, most of the companies that were planning to be in Chicago have “now transitioned to creating a virtual booth that people who are participating in the virtual meeting can visit.

“I don’t know exactly how each company is going to use their time and their virtual space, and that’s part of the whole learning process here to see how this whole experiment is going to work out,” he added.

Unlike some of the other conferences that have gone virtual, in which access has been made available to everyone for free, registration is still required for the ASCO meeting. But the society notes that the registration fee has been discounted for nonmembers and has been waived for ASCO members. Also, the fee covers both the Virtual Scientific Program in May and the ASCO Educational Program in August.

Registrants will have access to video and slide presentations, as well as discussant commentaries, for 180 days.

The article first appeared on Medscape.com.