Melanoma

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

Application of an investigative topical cannabidiol (CBD) cream to buttock skin demonstrated protective properties against ultraviolet A (UVA) radiation-induced DNA and mitochondrial DNA damage, results from a small prospective pilot study showed.

“This study hopefully reinvigorates interest in the utilization of whether it be plant-based, human-derived, or synthetic cannabinoids in the management of dermatologic disease,” one of the study investigators, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization. The study was published in the Journal of the American Academy of Dermatology.

George Washington University

For the prospective, single-center, pilot trial, which is believed to be the first of its kind, 19 volunteers aged 22-65 with Fitzpatrick skin types I-III applied either a nano-encapsulated CBD cream or a vehicle cream to blind spots on the skin of the buttocks twice daily for 14 days. Next, researchers applied a minimal erythema dose of UV radiation to the treated skin areas for 30 minutes. After 24 hours, they visually inspected the treated areas to clinically compare the erythema. They also performed five 4-mm punch biopsies from UVA- and non-UVA–exposed treatment sites on each buttock, as well as from an untreated control site that was at least 5 cm away from the treated left buttock.

At 24 hours, 21% of study participants showed less redness on CBD-treated skin compared with control-treated skin, while histology showed that CBD-treated skin demonstrated reduced UVA-induced epidermal hyperplasia compared with control-treated skin (a mean 11.3% change from baseline vs 28.7%, respectively; P = .01). In other findings, application of CBD cream reduced DNA damage and DNA mutations associated with UVA-induced skin aging/damage and ultimately skin cancer.

In addition, the CBD-treated skin samples had a reduction in the UVA-associated increase in the premutagenic marker 8-oxoguanine DNA glycosylase 1 and a reduction of two major UVA-induced mitochondrial DNA deletions associated with skin photoaging.

The research, Dr. Friedman noted, “took a village of collaborators and almost 3 years to pull together,” including collaborating with his long-standing mentor, Brian Berman, MD, PhD, professor emeritus of dermatology and dermatologic surgery at the University of Miami, Coral Gables, Florida, and a study coauthor. The study “demonstrated that purposeful delivery of CBD using an established nanoparticle platform ... can have a quantifiable impact on preventing the expected DNA damage and cellular injury one should see from UVA exposure,” said Dr. Friedman, who codeveloped the nanoparticle platform with his father, Joel M. Friedman, MD, PhD, professor of microbiology and immunology at Albert Einstein College of Medicine, New York City.

“Never before has a dermatologic study on topical cannabinoids dove so deeply into the biological impact of this natural ingredient to highlight its potential, here, as a mitigation strategy for unprotected exposure to prevent the downstream sequelae of UV radiation,” Dr. Friedman said.

In the paper, he and his coauthors acknowledged certain limitations of their study, including its small sample size and the single-center design.

Dr. Friedman disclosed that he coinvented the nanoparticle technology used in the trial. Dr. Berman is a consultant at MINO Labs, which funded the study. The remaining authors had no disclosures. The study was done in collaboration with the Center for Clinical and Cosmetic Research in Aventura, Florida.

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

Application of an investigative topical cannabidiol (CBD) cream to buttock skin demonstrated protective properties against ultraviolet A (UVA) radiation-induced DNA and mitochondrial DNA damage, results from a small prospective pilot study showed.

“This study hopefully reinvigorates interest in the utilization of whether it be plant-based, human-derived, or synthetic cannabinoids in the management of dermatologic disease,” one of the study investigators, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization. The study was published in the Journal of the American Academy of Dermatology.

George Washington University

For the prospective, single-center, pilot trial, which is believed to be the first of its kind, 19 volunteers aged 22-65 with Fitzpatrick skin types I-III applied either a nano-encapsulated CBD cream or a vehicle cream to blind spots on the skin of the buttocks twice daily for 14 days. Next, researchers applied a minimal erythema dose of UV radiation to the treated skin areas for 30 minutes. After 24 hours, they visually inspected the treated areas to clinically compare the erythema. They also performed five 4-mm punch biopsies from UVA- and non-UVA–exposed treatment sites on each buttock, as well as from an untreated control site that was at least 5 cm away from the treated left buttock.

At 24 hours, 21% of study participants showed less redness on CBD-treated skin compared with control-treated skin, while histology showed that CBD-treated skin demonstrated reduced UVA-induced epidermal hyperplasia compared with control-treated skin (a mean 11.3% change from baseline vs 28.7%, respectively; P = .01). In other findings, application of CBD cream reduced DNA damage and DNA mutations associated with UVA-induced skin aging/damage and ultimately skin cancer.

In addition, the CBD-treated skin samples had a reduction in the UVA-associated increase in the premutagenic marker 8-oxoguanine DNA glycosylase 1 and a reduction of two major UVA-induced mitochondrial DNA deletions associated with skin photoaging.

The research, Dr. Friedman noted, “took a village of collaborators and almost 3 years to pull together,” including collaborating with his long-standing mentor, Brian Berman, MD, PhD, professor emeritus of dermatology and dermatologic surgery at the University of Miami, Coral Gables, Florida, and a study coauthor. The study “demonstrated that purposeful delivery of CBD using an established nanoparticle platform ... can have a quantifiable impact on preventing the expected DNA damage and cellular injury one should see from UVA exposure,” said Dr. Friedman, who codeveloped the nanoparticle platform with his father, Joel M. Friedman, MD, PhD, professor of microbiology and immunology at Albert Einstein College of Medicine, New York City.

“Never before has a dermatologic study on topical cannabinoids dove so deeply into the biological impact of this natural ingredient to highlight its potential, here, as a mitigation strategy for unprotected exposure to prevent the downstream sequelae of UV radiation,” Dr. Friedman said.

In the paper, he and his coauthors acknowledged certain limitations of their study, including its small sample size and the single-center design.

Dr. Friedman disclosed that he coinvented the nanoparticle technology used in the trial. Dr. Berman is a consultant at MINO Labs, which funded the study. The remaining authors had no disclosures. The study was done in collaboration with the Center for Clinical and Cosmetic Research in Aventura, Florida.

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

Application of an investigative topical cannabidiol (CBD) cream to buttock skin demonstrated protective properties against ultraviolet A (UVA) radiation-induced DNA and mitochondrial DNA damage, results from a small prospective pilot study showed.

“This study hopefully reinvigorates interest in the utilization of whether it be plant-based, human-derived, or synthetic cannabinoids in the management of dermatologic disease,” one of the study investigators, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization. The study was published in the Journal of the American Academy of Dermatology.

George Washington University

For the prospective, single-center, pilot trial, which is believed to be the first of its kind, 19 volunteers aged 22-65 with Fitzpatrick skin types I-III applied either a nano-encapsulated CBD cream or a vehicle cream to blind spots on the skin of the buttocks twice daily for 14 days. Next, researchers applied a minimal erythema dose of UV radiation to the treated skin areas for 30 minutes. After 24 hours, they visually inspected the treated areas to clinically compare the erythema. They also performed five 4-mm punch biopsies from UVA- and non-UVA–exposed treatment sites on each buttock, as well as from an untreated control site that was at least 5 cm away from the treated left buttock.

At 24 hours, 21% of study participants showed less redness on CBD-treated skin compared with control-treated skin, while histology showed that CBD-treated skin demonstrated reduced UVA-induced epidermal hyperplasia compared with control-treated skin (a mean 11.3% change from baseline vs 28.7%, respectively; P = .01). In other findings, application of CBD cream reduced DNA damage and DNA mutations associated with UVA-induced skin aging/damage and ultimately skin cancer.

In addition, the CBD-treated skin samples had a reduction in the UVA-associated increase in the premutagenic marker 8-oxoguanine DNA glycosylase 1 and a reduction of two major UVA-induced mitochondrial DNA deletions associated with skin photoaging.

The research, Dr. Friedman noted, “took a village of collaborators and almost 3 years to pull together,” including collaborating with his long-standing mentor, Brian Berman, MD, PhD, professor emeritus of dermatology and dermatologic surgery at the University of Miami, Coral Gables, Florida, and a study coauthor. The study “demonstrated that purposeful delivery of CBD using an established nanoparticle platform ... can have a quantifiable impact on preventing the expected DNA damage and cellular injury one should see from UVA exposure,” said Dr. Friedman, who codeveloped the nanoparticle platform with his father, Joel M. Friedman, MD, PhD, professor of microbiology and immunology at Albert Einstein College of Medicine, New York City.

“Never before has a dermatologic study on topical cannabinoids dove so deeply into the biological impact of this natural ingredient to highlight its potential, here, as a mitigation strategy for unprotected exposure to prevent the downstream sequelae of UV radiation,” Dr. Friedman said.

In the paper, he and his coauthors acknowledged certain limitations of their study, including its small sample size and the single-center design.

Dr. Friedman disclosed that he coinvented the nanoparticle technology used in the trial. Dr. Berman is a consultant at MINO Labs, which funded the study. The remaining authors had no disclosures. The study was done in collaboration with the Center for Clinical and Cosmetic Research in Aventura, Florida.

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

To the Editor:

Immune checkpoint inhibitors have revolutionized the treatment of advanced-stage melanoma, with remarkably improved progression-free survival.¹ Anti–programmed death receptor 1 (anti–PD-1) therapies, such as nivolumab and pembrolizumab, are a class of checkpoint inhibitors that have been approved by the US Food and Drug Administration for unresectable metastatic melanoma. Anti–PD-1 agents block the interaction of programmed death-ligand 1 (PD-L1) found on tumor cells with the PD-1 receptor on T cells, facilitating a positive immune response.²

Although these therapies have demonstrated notable antitumor efficacy, they also give rise to numerous immune-related adverse events (irAEs). As many as 70% of patients treated with PD-1/PD-L1 inhibitors experience some type of organ system irAE, of which 30% to 40% are cutaneous.^3-6 Dermatologic adverse events are the most common irAEs, specifically spongiotic dermatitis, lichenoid dermatitis, pruritus, and vitiligo.⁷ Bullous pemphigoid (BP), an autoimmune bullous skin disorder caused by autoantibodies to basement membrane zone antigens, is a rare but potentially serious cutaneous irAE.⁸ Systemic corticosteroids commonly are used to treat immune checkpoint inhibitor–induced BP; other options include tetracyclines for maintenance therapy and rituximab for corticosteroid-refractory BP associated with anti-PD-1.⁹ We present a case of recalcitrant BP secondary to nivolumab therapy in a patient with metastatic melanoma who had near-complete resolution of BP following 2 months of cyclosporine.

A 41-year-old man presented with a generalized papular skin eruption of 1 month’s duration. He had a history of stage IIIC malignant melanoma of the lower right leg with positive sentinel lymph node biopsy. The largest lymph node deposit was 0.03 mm without extracapsular extension. Whole-body positron emission tomography–computed tomography showed no evidence of distant disease. The patient was treated with wide local excision with clear surgical margins plus 12 cycles of nivolumab, which was discontinued due to colitis. Four months after the final cycle of nivolumab, the patient developed widespread erythematous papules with hemorrhagic yellow crusting and no mucosal involvement. He was referred to dermatology by his primary oncologist for further evaluation.

A punch biopsy from the abdomen showed para­keratosis with leukocytoclasis and a superficial dermal infiltrate of neutrophils and eosinophils (Figure 1). Direct immunofluorescence revealed linear basement membrane deposits of IgG and C3, consistent with subepidermal blistering disease. Indirect immunofluorescence demonstrated trace IgG and IgG4 antibodies localized to the epidermal roof of salt-split skin and was negative for IgA antibodies. An enzyme-linked immunoassay was positive for BP antigen 2 (BP180) antibodies (98.4 U/mL [positive, ≥9 U/mL]) and negative for BP antigen 1 (BP230) antibodies (4.3 U/mL [positive, ≥9 U/mL]). Overall, these findings were consistent with a diagnosis of BP.

The patient was treated with prednisone 60 mg daily with initial response; however, there was disease recurrence with tapering. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily were added as steroid-sparing agents, as prednisone was discontinued due to mood changes. Three months after the prednisone taper, the patient continued to develop new blisters. He completed treatment with doxycycline and nicotinamide. Rituximab 375 mg weekly was then initiated for 4 weeks.

At 2-week follow-up after completing the rituximab course, the patient reported worsening symptoms and presented with new bullae on the abdomen and upper extremities (Figure 2). Because of the recent history of mood changes while taking prednisone, a trial of cyclosporine 100 mg twice daily (1.37 mg/kg/d) was initiated, with notable improvement within 2 weeks of treatment. After 2 months of cyclosporine, approximately 90% of the rash had resolved with a few tense bullae remaining on the left frontal scalp but no new flares (Figure 3). One month after treatment ended, the patient remained clear of lesions without relapse.

Programmed death receptor 1 inhibitors have shown dramatic efficacy for a growing number of solid and hematologic malignancies, especially malignant melanoma. However, their use is accompanied by nonspecific activation of the immune system, resulting in a variety of adverse events, many manifesting on the skin. Several cases of BP in patients treated with PD-1/PD-L1 inhibitors have been reported.⁹ Cutaneous irAEs usually manifest within 3 weeks of initiation of PD-1 inhibitor therapy; however, the onset of BP typically occurs later at approximately 21 weeks.^4,9 Our patient developed cutaneous manifestations 4 months after cessation of nivolumab.

To the Editor:

Immune checkpoint inhibitors have revolutionized the treatment of advanced-stage melanoma, with remarkably improved progression-free survival.¹ Anti–programmed death receptor 1 (anti–PD-1) therapies, such as nivolumab and pembrolizumab, are a class of checkpoint inhibitors that have been approved by the US Food and Drug Administration for unresectable metastatic melanoma. Anti–PD-1 agents block the interaction of programmed death-ligand 1 (PD-L1) found on tumor cells with the PD-1 receptor on T cells, facilitating a positive immune response.²

Although these therapies have demonstrated notable antitumor efficacy, they also give rise to numerous immune-related adverse events (irAEs). As many as 70% of patients treated with PD-1/PD-L1 inhibitors experience some type of organ system irAE, of which 30% to 40% are cutaneous.^3-6 Dermatologic adverse events are the most common irAEs, specifically spongiotic dermatitis, lichenoid dermatitis, pruritus, and vitiligo.⁷ Bullous pemphigoid (BP), an autoimmune bullous skin disorder caused by autoantibodies to basement membrane zone antigens, is a rare but potentially serious cutaneous irAE.⁸ Systemic corticosteroids commonly are used to treat immune checkpoint inhibitor–induced BP; other options include tetracyclines for maintenance therapy and rituximab for corticosteroid-refractory BP associated with anti-PD-1.⁹ We present a case of recalcitrant BP secondary to nivolumab therapy in a patient with metastatic melanoma who had near-complete resolution of BP following 2 months of cyclosporine.

A 41-year-old man presented with a generalized papular skin eruption of 1 month’s duration. He had a history of stage IIIC malignant melanoma of the lower right leg with positive sentinel lymph node biopsy. The largest lymph node deposit was 0.03 mm without extracapsular extension. Whole-body positron emission tomography–computed tomography showed no evidence of distant disease. The patient was treated with wide local excision with clear surgical margins plus 12 cycles of nivolumab, which was discontinued due to colitis. Four months after the final cycle of nivolumab, the patient developed widespread erythematous papules with hemorrhagic yellow crusting and no mucosal involvement. He was referred to dermatology by his primary oncologist for further evaluation.

A punch biopsy from the abdomen showed para­keratosis with leukocytoclasis and a superficial dermal infiltrate of neutrophils and eosinophils (Figure 1). Direct immunofluorescence revealed linear basement membrane deposits of IgG and C3, consistent with subepidermal blistering disease. Indirect immunofluorescence demonstrated trace IgG and IgG4 antibodies localized to the epidermal roof of salt-split skin and was negative for IgA antibodies. An enzyme-linked immunoassay was positive for BP antigen 2 (BP180) antibodies (98.4 U/mL [positive, ≥9 U/mL]) and negative for BP antigen 1 (BP230) antibodies (4.3 U/mL [positive, ≥9 U/mL]). Overall, these findings were consistent with a diagnosis of BP.

The patient was treated with prednisone 60 mg daily with initial response; however, there was disease recurrence with tapering. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily were added as steroid-sparing agents, as prednisone was discontinued due to mood changes. Three months after the prednisone taper, the patient continued to develop new blisters. He completed treatment with doxycycline and nicotinamide. Rituximab 375 mg weekly was then initiated for 4 weeks.

At 2-week follow-up after completing the rituximab course, the patient reported worsening symptoms and presented with new bullae on the abdomen and upper extremities (Figure 2). Because of the recent history of mood changes while taking prednisone, a trial of cyclosporine 100 mg twice daily (1.37 mg/kg/d) was initiated, with notable improvement within 2 weeks of treatment. After 2 months of cyclosporine, approximately 90% of the rash had resolved with a few tense bullae remaining on the left frontal scalp but no new flares (Figure 3). One month after treatment ended, the patient remained clear of lesions without relapse.

Programmed death receptor 1 inhibitors have shown dramatic efficacy for a growing number of solid and hematologic malignancies, especially malignant melanoma. However, their use is accompanied by nonspecific activation of the immune system, resulting in a variety of adverse events, many manifesting on the skin. Several cases of BP in patients treated with PD-1/PD-L1 inhibitors have been reported.⁹ Cutaneous irAEs usually manifest within 3 weeks of initiation of PD-1 inhibitor therapy; however, the onset of BP typically occurs later at approximately 21 weeks.^4,9 Our patient developed cutaneous manifestations 4 months after cessation of nivolumab.

To the Editor:

Immune checkpoint inhibitors have revolutionized the treatment of advanced-stage melanoma, with remarkably improved progression-free survival.¹ Anti–programmed death receptor 1 (anti–PD-1) therapies, such as nivolumab and pembrolizumab, are a class of checkpoint inhibitors that have been approved by the US Food and Drug Administration for unresectable metastatic melanoma. Anti–PD-1 agents block the interaction of programmed death-ligand 1 (PD-L1) found on tumor cells with the PD-1 receptor on T cells, facilitating a positive immune response.²

Although these therapies have demonstrated notable antitumor efficacy, they also give rise to numerous immune-related adverse events (irAEs). As many as 70% of patients treated with PD-1/PD-L1 inhibitors experience some type of organ system irAE, of which 30% to 40% are cutaneous.^3-6 Dermatologic adverse events are the most common irAEs, specifically spongiotic dermatitis, lichenoid dermatitis, pruritus, and vitiligo.⁷ Bullous pemphigoid (BP), an autoimmune bullous skin disorder caused by autoantibodies to basement membrane zone antigens, is a rare but potentially serious cutaneous irAE.⁸ Systemic corticosteroids commonly are used to treat immune checkpoint inhibitor–induced BP; other options include tetracyclines for maintenance therapy and rituximab for corticosteroid-refractory BP associated with anti-PD-1.⁹ We present a case of recalcitrant BP secondary to nivolumab therapy in a patient with metastatic melanoma who had near-complete resolution of BP following 2 months of cyclosporine.

A 41-year-old man presented with a generalized papular skin eruption of 1 month’s duration. He had a history of stage IIIC malignant melanoma of the lower right leg with positive sentinel lymph node biopsy. The largest lymph node deposit was 0.03 mm without extracapsular extension. Whole-body positron emission tomography–computed tomography showed no evidence of distant disease. The patient was treated with wide local excision with clear surgical margins plus 12 cycles of nivolumab, which was discontinued due to colitis. Four months after the final cycle of nivolumab, the patient developed widespread erythematous papules with hemorrhagic yellow crusting and no mucosal involvement. He was referred to dermatology by his primary oncologist for further evaluation.

A punch biopsy from the abdomen showed para­keratosis with leukocytoclasis and a superficial dermal infiltrate of neutrophils and eosinophils (Figure 1). Direct immunofluorescence revealed linear basement membrane deposits of IgG and C3, consistent with subepidermal blistering disease. Indirect immunofluorescence demonstrated trace IgG and IgG4 antibodies localized to the epidermal roof of salt-split skin and was negative for IgA antibodies. An enzyme-linked immunoassay was positive for BP antigen 2 (BP180) antibodies (98.4 U/mL [positive, ≥9 U/mL]) and negative for BP antigen 1 (BP230) antibodies (4.3 U/mL [positive, ≥9 U/mL]). Overall, these findings were consistent with a diagnosis of BP.

The patient was treated with prednisone 60 mg daily with initial response; however, there was disease recurrence with tapering. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily were added as steroid-sparing agents, as prednisone was discontinued due to mood changes. Three months after the prednisone taper, the patient continued to develop new blisters. He completed treatment with doxycycline and nicotinamide. Rituximab 375 mg weekly was then initiated for 4 weeks.

At 2-week follow-up after completing the rituximab course, the patient reported worsening symptoms and presented with new bullae on the abdomen and upper extremities (Figure 2). Because of the recent history of mood changes while taking prednisone, a trial of cyclosporine 100 mg twice daily (1.37 mg/kg/d) was initiated, with notable improvement within 2 weeks of treatment. After 2 months of cyclosporine, approximately 90% of the rash had resolved with a few tense bullae remaining on the left frontal scalp but no new flares (Figure 3). One month after treatment ended, the patient remained clear of lesions without relapse.

Programmed death receptor 1 inhibitors have shown dramatic efficacy for a growing number of solid and hematologic malignancies, especially malignant melanoma. However, their use is accompanied by nonspecific activation of the immune system, resulting in a variety of adverse events, many manifesting on the skin. Several cases of BP in patients treated with PD-1/PD-L1 inhibitors have been reported.⁹ Cutaneous irAEs usually manifest within 3 weeks of initiation of PD-1 inhibitor therapy; however, the onset of BP typically occurs later at approximately 21 weeks.^4,9 Our patient developed cutaneous manifestations 4 months after cessation of nivolumab.

Lifetime skin cancer prevalence in sexual minority (SM) Americans varied by race, ethnicity, and individual sexual identity, compared with that in heterosexual peers, according to a large cross-sectional study. Addressing dynamics of each SM subgroup will require increasingly tailored prevention, screening, and research efforts, the study authors said.

“We identified specific subgroups within the sexual minority community who are at higher risk for skin cancer, specifically White gay males and Hispanic and non-Hispanic Black SM men and women — particularly individuals who identify as bisexual,” senior author Matthew Mansh, MD, said in an interview. He is an assistant professor of dermatology at the University of California, San Francisco. The study was published online in JAMA Dermatology.

Using data of adults in the US general population from the Behavioral Risk Factor Surveillance System from January 2014 to December 2021, investigators included more than 1.5 million respondents. The proportions of SM women and men (who self-identified as bisexual, lesbian, gay, “something else,” or other) were 2.6% and 2.0%, respectively.

Lifetime skin cancer prevalence was higher among SM men than among heterosexual men (7.4% vs 6.8%; adjusted odds ratio [aOR], 1.16). In analyses stratified by racial and ethnic group, AORs for non-Hispanic Black and Hispanic SM men vs their heterosexual counterparts were 2.18 and 3.81, respectively. The corresponding figures for non-Hispanic Black and Hispanic SM women were 2.33 and 2.46, respectively.

When investigators combined all minority respondents along gender lines, lifetime skin cancer prevalence was higher in bisexual men (aOR, 3.94), bisexual women (aOR, 1.51), and women identifying as something else or other (aOR, 2.70) than in their heterosexual peers.

“I wasn’t expecting that Hispanic or non-Hispanic Black SMs would be at higher risk for skin cancer,” Dr. Mansh said. Even if these groups have more behavioral risk factors for UV radiation (UVR) exposure, he explained, UVR exposure is less strongly linked with skin cancer in darker skin than in lighter skin. Reasons for the counterintuitive finding could include different screening habits among SM people of different racial and ethnic groups, he said, and analyzing such factors will require further research.

Although some effect sizes were modest, the authors wrote, their findings may have important implications for population-based research and public health efforts aimed at early skin cancer detection and prevention. Presently, the United States lacks established guidelines for skin cancer screening. In a 2023 statement published in JAMA, the US Preventive Services Task Force said that there is insufficient evidence to determine the benefit-harm balance of skin cancer screening in asymptomatic people.

“So there has been a lot of recent talk and a need to identify which subset groups of patients might be higher risk for skin cancer and might benefit from more screening,” Dr. Mansh said in an interview. “Understanding more about the high-risk demographic and clinical features that predispose someone to skin cancer helps identify these high-risk populations that could be used to develop better screening guidelines.”

Identifying groups at a higher risk for skin cancer also allows experts to design more targeted counseling or public health interventions focused on these groups, Dr. Mansh added. Absent screening guidelines, experts emphasize changing modifiable risk factors such as UVR exposure, smoking, and alcohol use. “And we know that the message that might change behaviors in a cisgender heterosexual man might be different than in a gay White male or a Hispanic bisexual male.”

A 2017 review showed that interventions to reduce behaviors involving UVR exposure, such as indoor tanning, among young cisgender women focused largely on aging and appearance-based concerns. A 2019 study showed that messages focused on avoiding skin cancer may help motivate SM men to reduce tanning behaviors.

Furthermore, said Dr. Mansh, all electronic health record products available in the United States must provide data fields for sexual orientation. “I don’t believe many dermatologists, depending on the setting, collect that information routinely. Integrating sexual orientation and/or gender identity data into patient intake forms so that it can be integrated into the electronic health record is probably very helpful, not only for your clinical practice but also for future research studies.”

Asked to comment on the results, Rebecca I. Hartman, MD, MPH, who was not involved with the study, said that its impact on clinical practice will be challenging to ascertain. She is chief of dermatology with the VA Boston Healthcare System, assistant professor of dermatology at Harvard Medical School, and director of melanoma epidemiology at Brigham and Women’s Hospital, all in Boston, Massachusetts.

“The study found significant adjusted odds ratios,” Dr. Hartman explained, “but for some of the different populations, the overall lifetime rate of skin cancer is still quite low.” For example, 1.0% for SM non-Hispanic Black men or a difference of 2.1% vs 1.8% in SM Hispanic women. “Thus, I am not sure specific screening recommendations are warranted, although some populations, such as Hispanic sexual minority males, seemed to have a much higher risk (3.8-fold on adjusted analysis) that warrants further investigation.”

For now, she advised assessing patients’ risks for skin cancer based on well-established risk factors such as sun exposure/indoor tanning, skin phototype, immunosuppression, and age.

Dr. Mansh reported no relevant conflicts or funding sources for the study. Dr. Hartman reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Lifetime skin cancer prevalence in sexual minority (SM) Americans varied by race, ethnicity, and individual sexual identity, compared with that in heterosexual peers, according to a large cross-sectional study. Addressing dynamics of each SM subgroup will require increasingly tailored prevention, screening, and research efforts, the study authors said.

“We identified specific subgroups within the sexual minority community who are at higher risk for skin cancer, specifically White gay males and Hispanic and non-Hispanic Black SM men and women — particularly individuals who identify as bisexual,” senior author Matthew Mansh, MD, said in an interview. He is an assistant professor of dermatology at the University of California, San Francisco. The study was published online in JAMA Dermatology.

Using data of adults in the US general population from the Behavioral Risk Factor Surveillance System from January 2014 to December 2021, investigators included more than 1.5 million respondents. The proportions of SM women and men (who self-identified as bisexual, lesbian, gay, “something else,” or other) were 2.6% and 2.0%, respectively.

Lifetime skin cancer prevalence was higher among SM men than among heterosexual men (7.4% vs 6.8%; adjusted odds ratio [aOR], 1.16). In analyses stratified by racial and ethnic group, AORs for non-Hispanic Black and Hispanic SM men vs their heterosexual counterparts were 2.18 and 3.81, respectively. The corresponding figures for non-Hispanic Black and Hispanic SM women were 2.33 and 2.46, respectively.

When investigators combined all minority respondents along gender lines, lifetime skin cancer prevalence was higher in bisexual men (aOR, 3.94), bisexual women (aOR, 1.51), and women identifying as something else or other (aOR, 2.70) than in their heterosexual peers.

“I wasn’t expecting that Hispanic or non-Hispanic Black SMs would be at higher risk for skin cancer,” Dr. Mansh said. Even if these groups have more behavioral risk factors for UV radiation (UVR) exposure, he explained, UVR exposure is less strongly linked with skin cancer in darker skin than in lighter skin. Reasons for the counterintuitive finding could include different screening habits among SM people of different racial and ethnic groups, he said, and analyzing such factors will require further research.

Although some effect sizes were modest, the authors wrote, their findings may have important implications for population-based research and public health efforts aimed at early skin cancer detection and prevention. Presently, the United States lacks established guidelines for skin cancer screening. In a 2023 statement published in JAMA, the US Preventive Services Task Force said that there is insufficient evidence to determine the benefit-harm balance of skin cancer screening in asymptomatic people.

“So there has been a lot of recent talk and a need to identify which subset groups of patients might be higher risk for skin cancer and might benefit from more screening,” Dr. Mansh said in an interview. “Understanding more about the high-risk demographic and clinical features that predispose someone to skin cancer helps identify these high-risk populations that could be used to develop better screening guidelines.”

Identifying groups at a higher risk for skin cancer also allows experts to design more targeted counseling or public health interventions focused on these groups, Dr. Mansh added. Absent screening guidelines, experts emphasize changing modifiable risk factors such as UVR exposure, smoking, and alcohol use. “And we know that the message that might change behaviors in a cisgender heterosexual man might be different than in a gay White male or a Hispanic bisexual male.”

A 2017 review showed that interventions to reduce behaviors involving UVR exposure, such as indoor tanning, among young cisgender women focused largely on aging and appearance-based concerns. A 2019 study showed that messages focused on avoiding skin cancer may help motivate SM men to reduce tanning behaviors.

Furthermore, said Dr. Mansh, all electronic health record products available in the United States must provide data fields for sexual orientation. “I don’t believe many dermatologists, depending on the setting, collect that information routinely. Integrating sexual orientation and/or gender identity data into patient intake forms so that it can be integrated into the electronic health record is probably very helpful, not only for your clinical practice but also for future research studies.”

Asked to comment on the results, Rebecca I. Hartman, MD, MPH, who was not involved with the study, said that its impact on clinical practice will be challenging to ascertain. She is chief of dermatology with the VA Boston Healthcare System, assistant professor of dermatology at Harvard Medical School, and director of melanoma epidemiology at Brigham and Women’s Hospital, all in Boston, Massachusetts.

“The study found significant adjusted odds ratios,” Dr. Hartman explained, “but for some of the different populations, the overall lifetime rate of skin cancer is still quite low.” For example, 1.0% for SM non-Hispanic Black men or a difference of 2.1% vs 1.8% in SM Hispanic women. “Thus, I am not sure specific screening recommendations are warranted, although some populations, such as Hispanic sexual minority males, seemed to have a much higher risk (3.8-fold on adjusted analysis) that warrants further investigation.”

For now, she advised assessing patients’ risks for skin cancer based on well-established risk factors such as sun exposure/indoor tanning, skin phototype, immunosuppression, and age.

Dr. Mansh reported no relevant conflicts or funding sources for the study. Dr. Hartman reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Lifetime skin cancer prevalence in sexual minority (SM) Americans varied by race, ethnicity, and individual sexual identity, compared with that in heterosexual peers, according to a large cross-sectional study. Addressing dynamics of each SM subgroup will require increasingly tailored prevention, screening, and research efforts, the study authors said.

“We identified specific subgroups within the sexual minority community who are at higher risk for skin cancer, specifically White gay males and Hispanic and non-Hispanic Black SM men and women — particularly individuals who identify as bisexual,” senior author Matthew Mansh, MD, said in an interview. He is an assistant professor of dermatology at the University of California, San Francisco. The study was published online in JAMA Dermatology.

Using data of adults in the US general population from the Behavioral Risk Factor Surveillance System from January 2014 to December 2021, investigators included more than 1.5 million respondents. The proportions of SM women and men (who self-identified as bisexual, lesbian, gay, “something else,” or other) were 2.6% and 2.0%, respectively.

Lifetime skin cancer prevalence was higher among SM men than among heterosexual men (7.4% vs 6.8%; adjusted odds ratio [aOR], 1.16). In analyses stratified by racial and ethnic group, AORs for non-Hispanic Black and Hispanic SM men vs their heterosexual counterparts were 2.18 and 3.81, respectively. The corresponding figures for non-Hispanic Black and Hispanic SM women were 2.33 and 2.46, respectively.

When investigators combined all minority respondents along gender lines, lifetime skin cancer prevalence was higher in bisexual men (aOR, 3.94), bisexual women (aOR, 1.51), and women identifying as something else or other (aOR, 2.70) than in their heterosexual peers.

“I wasn’t expecting that Hispanic or non-Hispanic Black SMs would be at higher risk for skin cancer,” Dr. Mansh said. Even if these groups have more behavioral risk factors for UV radiation (UVR) exposure, he explained, UVR exposure is less strongly linked with skin cancer in darker skin than in lighter skin. Reasons for the counterintuitive finding could include different screening habits among SM people of different racial and ethnic groups, he said, and analyzing such factors will require further research.

Although some effect sizes were modest, the authors wrote, their findings may have important implications for population-based research and public health efforts aimed at early skin cancer detection and prevention. Presently, the United States lacks established guidelines for skin cancer screening. In a 2023 statement published in JAMA, the US Preventive Services Task Force said that there is insufficient evidence to determine the benefit-harm balance of skin cancer screening in asymptomatic people.

“So there has been a lot of recent talk and a need to identify which subset groups of patients might be higher risk for skin cancer and might benefit from more screening,” Dr. Mansh said in an interview. “Understanding more about the high-risk demographic and clinical features that predispose someone to skin cancer helps identify these high-risk populations that could be used to develop better screening guidelines.”

Identifying groups at a higher risk for skin cancer also allows experts to design more targeted counseling or public health interventions focused on these groups, Dr. Mansh added. Absent screening guidelines, experts emphasize changing modifiable risk factors such as UVR exposure, smoking, and alcohol use. “And we know that the message that might change behaviors in a cisgender heterosexual man might be different than in a gay White male or a Hispanic bisexual male.”

A 2017 review showed that interventions to reduce behaviors involving UVR exposure, such as indoor tanning, among young cisgender women focused largely on aging and appearance-based concerns. A 2019 study showed that messages focused on avoiding skin cancer may help motivate SM men to reduce tanning behaviors.

Furthermore, said Dr. Mansh, all electronic health record products available in the United States must provide data fields for sexual orientation. “I don’t believe many dermatologists, depending on the setting, collect that information routinely. Integrating sexual orientation and/or gender identity data into patient intake forms so that it can be integrated into the electronic health record is probably very helpful, not only for your clinical practice but also for future research studies.”

Asked to comment on the results, Rebecca I. Hartman, MD, MPH, who was not involved with the study, said that its impact on clinical practice will be challenging to ascertain. She is chief of dermatology with the VA Boston Healthcare System, assistant professor of dermatology at Harvard Medical School, and director of melanoma epidemiology at Brigham and Women’s Hospital, all in Boston, Massachusetts.

“The study found significant adjusted odds ratios,” Dr. Hartman explained, “but for some of the different populations, the overall lifetime rate of skin cancer is still quite low.” For example, 1.0% for SM non-Hispanic Black men or a difference of 2.1% vs 1.8% in SM Hispanic women. “Thus, I am not sure specific screening recommendations are warranted, although some populations, such as Hispanic sexual minority males, seemed to have a much higher risk (3.8-fold on adjusted analysis) that warrants further investigation.”

For now, she advised assessing patients’ risks for skin cancer based on well-established risk factors such as sun exposure/indoor tanning, skin phototype, immunosuppression, and age.

Dr. Mansh reported no relevant conflicts or funding sources for the study. Dr. Hartman reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Patients with treatment-refractory cancers who did not meet eligibility criteria for a pan-cancer clinical trial but received waivers allowing them to participate had similar outcomes to patients who participated without waivers, a new analysis revealed.

The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.

“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”

Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.

In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.

In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.

Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing. 

The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers. 

Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.

A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.

The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).

“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.

The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.

So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.

Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.

Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”

However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.

“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”

Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
 

A version of this article appeared on Medscape.com.

Patients with treatment-refractory cancers who did not meet eligibility criteria for a pan-cancer clinical trial but received waivers allowing them to participate had similar outcomes to patients who participated without waivers, a new analysis revealed.

The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.

“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”

Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.

In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.

In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.

Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing. 

The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers. 

Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.

A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.

The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).

“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.

The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.

So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.

Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.

Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”

However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.

“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”

Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
 

A version of this article appeared on Medscape.com.

Patients with treatment-refractory cancers who did not meet eligibility criteria for a pan-cancer clinical trial but received waivers allowing them to participate had similar outcomes to patients who participated without waivers, a new analysis revealed.

The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.

“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”

Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.

In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.

In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.

Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing. 

The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers. 

Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.

A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.

The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).

“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.

The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.

So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.

Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.

Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”

However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.

“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”

Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
 

A version of this article appeared on Medscape.com.