Breast Cancer

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:

Breast cancer immunotherapy trials yield modest clinical impact, with a quarter of trials failing to report their outcomes, particularly among single-center studies which are more likely to go unreported, and many phase 2 studies failing to translate into successful phase 3 trials.

METHODOLOGY:

• Few immunotherapy agents — only pembrolizumab in the United States, as of December 2023, and atezolizumab in Europe — have received approvals for use in patients with breast cancer, indicating low returns on the large number of breast cancer immunotherapy trials launched in the early 2010s.
• In this cross-sectional study, researchers evaluated 331 immunotherapy trials, initiated between January 2004 and April 2023, that enrolled 48,844 patients with breast cancer.
• Of these, 47 were phase 1 trials, 242 were phase 2 trials, and 42 were phase 3 trials.
• A trial was considered reported if the results were posted on ClinicalTrial.gov or reported as an abstract or a manuscript.
• Overall, 120 trials met their completion date up to November 2022; of these, 30 (25%) failed to report outcomes, which included two phase 3 trials.

TAKEAWAY:

• Phase 1 trials had the highest rate of nonreporting (31.8%), followed by phase 2 (23.6%) and phase 3 (22.2%) trials.
• Single-center studies were more likely to be unreported than multicenter studies (35.2% vs 15.0%; P = .02).
• Of 90 reported trials, 47 (52.2%) met their primary endpoints and 43 (47.8%) did not.
• The majority, 17 out of 19 (89.5%), of the reported randomized trials had negative results.

IN PRACTICE:

“The findings of this study suggest that the large number of immunotherapy trials being run have yielded modest clinical impact,” the authors wrote. “More selective initiation of phase 2 trials, grounded in preclinical and biomarker observations and with optimal statistical designs for early efficacy assessment, is needed to increase trial efficiency.” 

SOURCE:

The study, led by Marco Mariani, MD, Università Vita-Salute San Raffaele, Milan, Italy, was published online in JAMA Network Open. 

LIMITATIONS:

The study’s reliance on ClinicalTrials.gov as the primary source of trial data might have resulted in some trials being overlooked. In addition, manual data extraction could cause inaccuracies and potentially introduced biases in the interpretation of trial results. Primary study completion date cutoff of December 2022 could have excluded significant data from more recent trials.

DISCLOSURES:

This study received support via Susan Komen Leadership Grant and the Fondazione AIRC per la Ricerca sul Cancro. Several authors reported receiving grants and personal fees and having other ties with various sources.

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:

Breast cancer immunotherapy trials yield modest clinical impact, with a quarter of trials failing to report their outcomes, particularly among single-center studies which are more likely to go unreported, and many phase 2 studies failing to translate into successful phase 3 trials.

METHODOLOGY:

• Few immunotherapy agents — only pembrolizumab in the United States, as of December 2023, and atezolizumab in Europe — have received approvals for use in patients with breast cancer, indicating low returns on the large number of breast cancer immunotherapy trials launched in the early 2010s.
• In this cross-sectional study, researchers evaluated 331 immunotherapy trials, initiated between January 2004 and April 2023, that enrolled 48,844 patients with breast cancer.
• Of these, 47 were phase 1 trials, 242 were phase 2 trials, and 42 were phase 3 trials.
• A trial was considered reported if the results were posted on ClinicalTrial.gov or reported as an abstract or a manuscript.
• Overall, 120 trials met their completion date up to November 2022; of these, 30 (25%) failed to report outcomes, which included two phase 3 trials.

TAKEAWAY:

• Phase 1 trials had the highest rate of nonreporting (31.8%), followed by phase 2 (23.6%) and phase 3 (22.2%) trials.
• Single-center studies were more likely to be unreported than multicenter studies (35.2% vs 15.0%; P = .02).
• Of 90 reported trials, 47 (52.2%) met their primary endpoints and 43 (47.8%) did not.
• The majority, 17 out of 19 (89.5%), of the reported randomized trials had negative results.

IN PRACTICE:

“The findings of this study suggest that the large number of immunotherapy trials being run have yielded modest clinical impact,” the authors wrote. “More selective initiation of phase 2 trials, grounded in preclinical and biomarker observations and with optimal statistical designs for early efficacy assessment, is needed to increase trial efficiency.” 

SOURCE:

The study, led by Marco Mariani, MD, Università Vita-Salute San Raffaele, Milan, Italy, was published online in JAMA Network Open. 

LIMITATIONS:

The study’s reliance on ClinicalTrials.gov as the primary source of trial data might have resulted in some trials being overlooked. In addition, manual data extraction could cause inaccuracies and potentially introduced biases in the interpretation of trial results. Primary study completion date cutoff of December 2022 could have excluded significant data from more recent trials.

DISCLOSURES:

This study received support via Susan Komen Leadership Grant and the Fondazione AIRC per la Ricerca sul Cancro. Several authors reported receiving grants and personal fees and having other ties with various sources.

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:

Breast cancer immunotherapy trials yield modest clinical impact, with a quarter of trials failing to report their outcomes, particularly among single-center studies which are more likely to go unreported, and many phase 2 studies failing to translate into successful phase 3 trials.

METHODOLOGY:

• Few immunotherapy agents — only pembrolizumab in the United States, as of December 2023, and atezolizumab in Europe — have received approvals for use in patients with breast cancer, indicating low returns on the large number of breast cancer immunotherapy trials launched in the early 2010s.
• In this cross-sectional study, researchers evaluated 331 immunotherapy trials, initiated between January 2004 and April 2023, that enrolled 48,844 patients with breast cancer.
• Of these, 47 were phase 1 trials, 242 were phase 2 trials, and 42 were phase 3 trials.
• A trial was considered reported if the results were posted on ClinicalTrial.gov or reported as an abstract or a manuscript.
• Overall, 120 trials met their completion date up to November 2022; of these, 30 (25%) failed to report outcomes, which included two phase 3 trials.

TAKEAWAY:

• Phase 1 trials had the highest rate of nonreporting (31.8%), followed by phase 2 (23.6%) and phase 3 (22.2%) trials.
• Single-center studies were more likely to be unreported than multicenter studies (35.2% vs 15.0%; P = .02).
• Of 90 reported trials, 47 (52.2%) met their primary endpoints and 43 (47.8%) did not.
• The majority, 17 out of 19 (89.5%), of the reported randomized trials had negative results.

IN PRACTICE:

“The findings of this study suggest that the large number of immunotherapy trials being run have yielded modest clinical impact,” the authors wrote. “More selective initiation of phase 2 trials, grounded in preclinical and biomarker observations and with optimal statistical designs for early efficacy assessment, is needed to increase trial efficiency.” 

SOURCE:

The study, led by Marco Mariani, MD, Università Vita-Salute San Raffaele, Milan, Italy, was published online in JAMA Network Open. 

LIMITATIONS:

The study’s reliance on ClinicalTrials.gov as the primary source of trial data might have resulted in some trials being overlooked. In addition, manual data extraction could cause inaccuracies and potentially introduced biases in the interpretation of trial results. Primary study completion date cutoff of December 2022 could have excluded significant data from more recent trials.

DISCLOSURES:

This study received support via Susan Komen Leadership Grant and the Fondazione AIRC per la Ricerca sul Cancro. Several authors reported receiving grants and personal fees and having other ties with various sources.

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:

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.

The US Food and Drug Administration (FDA) has approved afamitresgene autoleucel (afami-cel) (Tecelra, Adaptimmune LLC) to treat advanced synovial sarcoma. 

Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.

The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.

Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities. 

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”

T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors. 

The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew. 

According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.

“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.

The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.

The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.

The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.

The list price for the one-time therapy is $727,000, according to Fierce Pharma.
 

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

The US Food and Drug Administration (FDA) has approved afamitresgene autoleucel (afami-cel) (Tecelra, Adaptimmune LLC) to treat advanced synovial sarcoma. 

Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.

The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.

Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities. 

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”

T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors. 

The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew. 

According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.

“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.

The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.

The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.

The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.

The list price for the one-time therapy is $727,000, according to Fierce Pharma.
 

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

The US Food and Drug Administration (FDA) has approved afamitresgene autoleucel (afami-cel) (Tecelra, Adaptimmune LLC) to treat advanced synovial sarcoma. 

Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.

The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.

Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities. 

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”

T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors. 

The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew. 

According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.

“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.

The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.

The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.

The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.

The list price for the one-time therapy is $727,000, according to Fierce Pharma.
 

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.

The CDK4/6 inhibitors abemaciclib and ribociclib were independently associated with better progression-free survival (PFS) when compared with palbociclib in a real-world comparison of the agents as first line treatment, along with endocrine therapy (ET), for patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Lead investigator Claudio Vernieri, MD, PhD, presented these findings of the PALMARES-2 study at the annual meeting of the American Society of Clinical Oncology.

“Along with different safety profiles, drug-drug interactions, and costs of the three available CDK4/6 inhibitor molecules, our efficacy data may help clinicians and patients in choosing the most appropriate CDK4/6 inhibitor in specific clinical contexts,” Dr. Vernieri, who is from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said during the meeting.

CDK4/6 inhibitors combined with ET, are the standard of care as first line treatment for this population, noted Dr. Vernieri. However, their efficacy has never been directly compared in a large clinical trial.

“Since these compounds have different pharmacokinetics, pharmacodynamics, safety profiles, costs, and drug-drug interactions, identifying which of the three CDK4/6 inhibitors may be more effective in specific clinical contexts is a highly clinically relevant issue,” he said. “Real-world data represent a key source to perform direct comparisons.”

The PALMARES-2 study was a retrospective, multicenter, population-based study, in 18 Italian cancer centers. Its two main objectives were to compare the real-world PFS of abemaciclib versus ribociclib versus palbociclib, in combination with ET, in the whole study cohort, as well as in various subgroups including patients with endocrine-resistant disease, luminal B-like disease, or in premenopausal women.

A total of 1,850 patients (median age, 63 years) were enrolled between January 1, 2016 and September 1, 2023, with 750 (40.6%) receiving palbociclib, and 676 (36.5%) and 424 (22.9%) receiving ribociclib and abemaciclib, respectively.
 

Baseline imbalance

Importantly, there were significant imbalances in baseline characteristics of the patients, with those receiving abemaciclib being more likely to have endocrine-resistant disease, low progesterone receptor expression, and liver metastasis, and less likely to have de novo metastatic disease, compared with other patients, said Dr. Vernieri.

The analysis showed that across the entire cohort, the median real-world PFS and overall survival (OS) were 34.7 months and 66.6 months, respectively, by a January 1, 2024, data cutoff date. “I believe that the overall survival data are still immature to make a definitive conclusion,” he commented, noting that at enrollment only about half of patients had undergone disease progression, and at the close of the study only about 25% had died.

After adjusting for clinically relevant patient- and tumor-related covariates, “we found that both abemaciclib and ribociclib were more effective than palbociclib, whereas we did not find statistically significant differences between abemaciclib and ribociclib,” he reported.

Specifically, the adjusted hazard ratio (aHR) for PFS was 0.71 for abemaciclib versus palbociclib (95% CI, 0.56-0.90; P = .005), 0.81 for ribociclib versus palbociclib (95% CI, 0.65-0.99; P = .048), and 0.91 for abemaciclib versus ribociclib (95% CI, 0.70-1.19; P = .505).

“Regarding subgroup analysis, we found that abemaciclib and ribociclib were more effective than palbociclib in patients with endocrine-resistant or luminal B-like disease, as well as in premenopausal women. Abemaciclib was superior to palbociclib in patients with poorer ECOG [Eastern Cooperative Oncology Group] performance status and to both palbociclib and ribociclib in patients with de novo metastatic disease. Both ribociclib and abemaciclib showed a trend toward higher efficacy in patients with liver metastases. However, this difference only reached statistical significance in patients treated with ribociclib. And finally, the three CDK4/6 inhibitors were similarly effective in patients who were older or at bone-only disease,” he concluded.
 

Justifying adjustment

Speaking during the audience question period Giuseppe Del Priore, MD, from Morehouse School of Medicine in Atlanta, Georgia, said he preferred unadjusted results when examining real-world data, “because that’s the benefit,” and he questioned why the researchers had adjusted their numbers.

Dr. Vernieri explained that the adjustments were made to account for the important imbalances in the baseline characteristics of the patients.

“When we plotted unadjusted curves, we did not find statistically significant differences between these three drugs, only a trend toward the direction that I showed you today,” he said. “However, as you saw from the tables showing the characteristics of patients, there were important imbalances in terms of important prognostic factors in the three patient cohorts. So, I think that, for this kind of data and based on this level of imbalance, adjustment is necessary.

“To reinforce our conclusions, what we did was also to perform a propensity score match–based analysis,” Dr. Vernieri continued. “I did not have the time to show the results today, but these data were fully in line with the study conclusions. And we also performed a backward selection of variables. So, we basically selected variables more likely to be associated with patient prognosis. And also those models confirm the study conclusion. So I think the conclusions are quite solid.”

Dr. Del Priore, an adjunct professor of obstetrics and gynecology with a specialty in oncology, on the other hand, said he was not convinced that any of the drugs might be better or worse in the actual population treated.

“I still maintain that unadjusted real-world data should be presented and then only a limited adjusted analysis performed using the most unbalanced variables,” he said. “To do more elaborate adjustments may falsely imply a difference in drug choice and outcomes which never should be the conclusion with observational studies. Instead, the conclusions should be that, with typical use, the following similarities in PFS and OS were observed. Then point out how drug choice and important prognostic variables might be linked, thus limiting the generalizable conclusions even further.

“I would conclude that prospective studies should balance for the variables used in the PALMARES-2 analyses, which actually may have been chosen for adjustment post hoc,” Dr. Del Priore said.

The study was funded by the Italian Association for Cancer Research, the European Research Council, the Ministero della Salute, the Scientific Directorate of Fondazione IRCCS Istituto Nazionale dei Tumori, Giuliani’s Foundation and Roche. Dr. Vernieri reported consulting or advisory roles with Daiichi Sankyo/Astra Zeneca, Novartis, and Pfizer; speakers’ bureau roles with Accademia Nazionale Di Medicina (ACCMED), Istituto Gentili, Lilly and Novartis; and research funding from Roche. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

The CDK4/6 inhibitors abemaciclib and ribociclib were independently associated with better progression-free survival (PFS) when compared with palbociclib in a real-world comparison of the agents as first line treatment, along with endocrine therapy (ET), for patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Lead investigator Claudio Vernieri, MD, PhD, presented these findings of the PALMARES-2 study at the annual meeting of the American Society of Clinical Oncology.

“Along with different safety profiles, drug-drug interactions, and costs of the three available CDK4/6 inhibitor molecules, our efficacy data may help clinicians and patients in choosing the most appropriate CDK4/6 inhibitor in specific clinical contexts,” Dr. Vernieri, who is from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said during the meeting.

CDK4/6 inhibitors combined with ET, are the standard of care as first line treatment for this population, noted Dr. Vernieri. However, their efficacy has never been directly compared in a large clinical trial.

“Since these compounds have different pharmacokinetics, pharmacodynamics, safety profiles, costs, and drug-drug interactions, identifying which of the three CDK4/6 inhibitors may be more effective in specific clinical contexts is a highly clinically relevant issue,” he said. “Real-world data represent a key source to perform direct comparisons.”

The PALMARES-2 study was a retrospective, multicenter, population-based study, in 18 Italian cancer centers. Its two main objectives were to compare the real-world PFS of abemaciclib versus ribociclib versus palbociclib, in combination with ET, in the whole study cohort, as well as in various subgroups including patients with endocrine-resistant disease, luminal B-like disease, or in premenopausal women.

A total of 1,850 patients (median age, 63 years) were enrolled between January 1, 2016 and September 1, 2023, with 750 (40.6%) receiving palbociclib, and 676 (36.5%) and 424 (22.9%) receiving ribociclib and abemaciclib, respectively.
 

Baseline imbalance

Importantly, there were significant imbalances in baseline characteristics of the patients, with those receiving abemaciclib being more likely to have endocrine-resistant disease, low progesterone receptor expression, and liver metastasis, and less likely to have de novo metastatic disease, compared with other patients, said Dr. Vernieri.

The analysis showed that across the entire cohort, the median real-world PFS and overall survival (OS) were 34.7 months and 66.6 months, respectively, by a January 1, 2024, data cutoff date. “I believe that the overall survival data are still immature to make a definitive conclusion,” he commented, noting that at enrollment only about half of patients had undergone disease progression, and at the close of the study only about 25% had died.

After adjusting for clinically relevant patient- and tumor-related covariates, “we found that both abemaciclib and ribociclib were more effective than palbociclib, whereas we did not find statistically significant differences between abemaciclib and ribociclib,” he reported.

Specifically, the adjusted hazard ratio (aHR) for PFS was 0.71 for abemaciclib versus palbociclib (95% CI, 0.56-0.90; P = .005), 0.81 for ribociclib versus palbociclib (95% CI, 0.65-0.99; P = .048), and 0.91 for abemaciclib versus ribociclib (95% CI, 0.70-1.19; P = .505).

“Regarding subgroup analysis, we found that abemaciclib and ribociclib were more effective than palbociclib in patients with endocrine-resistant or luminal B-like disease, as well as in premenopausal women. Abemaciclib was superior to palbociclib in patients with poorer ECOG [Eastern Cooperative Oncology Group] performance status and to both palbociclib and ribociclib in patients with de novo metastatic disease. Both ribociclib and abemaciclib showed a trend toward higher efficacy in patients with liver metastases. However, this difference only reached statistical significance in patients treated with ribociclib. And finally, the three CDK4/6 inhibitors were similarly effective in patients who were older or at bone-only disease,” he concluded.
 

Justifying adjustment

Speaking during the audience question period Giuseppe Del Priore, MD, from Morehouse School of Medicine in Atlanta, Georgia, said he preferred unadjusted results when examining real-world data, “because that’s the benefit,” and he questioned why the researchers had adjusted their numbers.

Dr. Vernieri explained that the adjustments were made to account for the important imbalances in the baseline characteristics of the patients.

“When we plotted unadjusted curves, we did not find statistically significant differences between these three drugs, only a trend toward the direction that I showed you today,” he said. “However, as you saw from the tables showing the characteristics of patients, there were important imbalances in terms of important prognostic factors in the three patient cohorts. So, I think that, for this kind of data and based on this level of imbalance, adjustment is necessary.

“To reinforce our conclusions, what we did was also to perform a propensity score match–based analysis,” Dr. Vernieri continued. “I did not have the time to show the results today, but these data were fully in line with the study conclusions. And we also performed a backward selection of variables. So, we basically selected variables more likely to be associated with patient prognosis. And also those models confirm the study conclusion. So I think the conclusions are quite solid.”

Dr. Del Priore, an adjunct professor of obstetrics and gynecology with a specialty in oncology, on the other hand, said he was not convinced that any of the drugs might be better or worse in the actual population treated.

“I still maintain that unadjusted real-world data should be presented and then only a limited adjusted analysis performed using the most unbalanced variables,” he said. “To do more elaborate adjustments may falsely imply a difference in drug choice and outcomes which never should be the conclusion with observational studies. Instead, the conclusions should be that, with typical use, the following similarities in PFS and OS were observed. Then point out how drug choice and important prognostic variables might be linked, thus limiting the generalizable conclusions even further.

“I would conclude that prospective studies should balance for the variables used in the PALMARES-2 analyses, which actually may have been chosen for adjustment post hoc,” Dr. Del Priore said.

The study was funded by the Italian Association for Cancer Research, the European Research Council, the Ministero della Salute, the Scientific Directorate of Fondazione IRCCS Istituto Nazionale dei Tumori, Giuliani’s Foundation and Roche. Dr. Vernieri reported consulting or advisory roles with Daiichi Sankyo/Astra Zeneca, Novartis, and Pfizer; speakers’ bureau roles with Accademia Nazionale Di Medicina (ACCMED), Istituto Gentili, Lilly and Novartis; and research funding from Roche. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

The CDK4/6 inhibitors abemaciclib and ribociclib were independently associated with better progression-free survival (PFS) when compared with palbociclib in a real-world comparison of the agents as first line treatment, along with endocrine therapy (ET), for patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Lead investigator Claudio Vernieri, MD, PhD, presented these findings of the PALMARES-2 study at the annual meeting of the American Society of Clinical Oncology.

“Along with different safety profiles, drug-drug interactions, and costs of the three available CDK4/6 inhibitor molecules, our efficacy data may help clinicians and patients in choosing the most appropriate CDK4/6 inhibitor in specific clinical contexts,” Dr. Vernieri, who is from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said during the meeting.

CDK4/6 inhibitors combined with ET, are the standard of care as first line treatment for this population, noted Dr. Vernieri. However, their efficacy has never been directly compared in a large clinical trial.

“Since these compounds have different pharmacokinetics, pharmacodynamics, safety profiles, costs, and drug-drug interactions, identifying which of the three CDK4/6 inhibitors may be more effective in specific clinical contexts is a highly clinically relevant issue,” he said. “Real-world data represent a key source to perform direct comparisons.”

The PALMARES-2 study was a retrospective, multicenter, population-based study, in 18 Italian cancer centers. Its two main objectives were to compare the real-world PFS of abemaciclib versus ribociclib versus palbociclib, in combination with ET, in the whole study cohort, as well as in various subgroups including patients with endocrine-resistant disease, luminal B-like disease, or in premenopausal women.

A total of 1,850 patients (median age, 63 years) were enrolled between January 1, 2016 and September 1, 2023, with 750 (40.6%) receiving palbociclib, and 676 (36.5%) and 424 (22.9%) receiving ribociclib and abemaciclib, respectively.
 

Baseline imbalance

Importantly, there were significant imbalances in baseline characteristics of the patients, with those receiving abemaciclib being more likely to have endocrine-resistant disease, low progesterone receptor expression, and liver metastasis, and less likely to have de novo metastatic disease, compared with other patients, said Dr. Vernieri.

The analysis showed that across the entire cohort, the median real-world PFS and overall survival (OS) were 34.7 months and 66.6 months, respectively, by a January 1, 2024, data cutoff date. “I believe that the overall survival data are still immature to make a definitive conclusion,” he commented, noting that at enrollment only about half of patients had undergone disease progression, and at the close of the study only about 25% had died.

After adjusting for clinically relevant patient- and tumor-related covariates, “we found that both abemaciclib and ribociclib were more effective than palbociclib, whereas we did not find statistically significant differences between abemaciclib and ribociclib,” he reported.

Specifically, the adjusted hazard ratio (aHR) for PFS was 0.71 for abemaciclib versus palbociclib (95% CI, 0.56-0.90; P = .005), 0.81 for ribociclib versus palbociclib (95% CI, 0.65-0.99; P = .048), and 0.91 for abemaciclib versus ribociclib (95% CI, 0.70-1.19; P = .505).

“Regarding subgroup analysis, we found that abemaciclib and ribociclib were more effective than palbociclib in patients with endocrine-resistant or luminal B-like disease, as well as in premenopausal women. Abemaciclib was superior to palbociclib in patients with poorer ECOG [Eastern Cooperative Oncology Group] performance status and to both palbociclib and ribociclib in patients with de novo metastatic disease. Both ribociclib and abemaciclib showed a trend toward higher efficacy in patients with liver metastases. However, this difference only reached statistical significance in patients treated with ribociclib. And finally, the three CDK4/6 inhibitors were similarly effective in patients who were older or at bone-only disease,” he concluded.
 

Justifying adjustment

Speaking during the audience question period Giuseppe Del Priore, MD, from Morehouse School of Medicine in Atlanta, Georgia, said he preferred unadjusted results when examining real-world data, “because that’s the benefit,” and he questioned why the researchers had adjusted their numbers.

Dr. Vernieri explained that the adjustments were made to account for the important imbalances in the baseline characteristics of the patients.

“When we plotted unadjusted curves, we did not find statistically significant differences between these three drugs, only a trend toward the direction that I showed you today,” he said. “However, as you saw from the tables showing the characteristics of patients, there were important imbalances in terms of important prognostic factors in the three patient cohorts. So, I think that, for this kind of data and based on this level of imbalance, adjustment is necessary.

“To reinforce our conclusions, what we did was also to perform a propensity score match–based analysis,” Dr. Vernieri continued. “I did not have the time to show the results today, but these data were fully in line with the study conclusions. And we also performed a backward selection of variables. So, we basically selected variables more likely to be associated with patient prognosis. And also those models confirm the study conclusion. So I think the conclusions are quite solid.”

Dr. Del Priore, an adjunct professor of obstetrics and gynecology with a specialty in oncology, on the other hand, said he was not convinced that any of the drugs might be better or worse in the actual population treated.

“I still maintain that unadjusted real-world data should be presented and then only a limited adjusted analysis performed using the most unbalanced variables,” he said. “To do more elaborate adjustments may falsely imply a difference in drug choice and outcomes which never should be the conclusion with observational studies. Instead, the conclusions should be that, with typical use, the following similarities in PFS and OS were observed. Then point out how drug choice and important prognostic variables might be linked, thus limiting the generalizable conclusions even further.

“I would conclude that prospective studies should balance for the variables used in the PALMARES-2 analyses, which actually may have been chosen for adjustment post hoc,” Dr. Del Priore said.

The study was funded by the Italian Association for Cancer Research, the European Research Council, the Ministero della Salute, the Scientific Directorate of Fondazione IRCCS Istituto Nazionale dei Tumori, Giuliani’s Foundation and Roche. Dr. Vernieri reported consulting or advisory roles with Daiichi Sankyo/Astra Zeneca, Novartis, and Pfizer; speakers’ bureau roles with Accademia Nazionale Di Medicina (ACCMED), Istituto Gentili, Lilly and Novartis; and research funding from Roche. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

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

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

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

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

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

CHICAGO — Being hormone receptor positive is generally a favorable prognostic factor in breast cancer, but that doesn’t seem to be the case in women with BRCA-associated tumors, according to a study presented at the American Society of Clinical Oncology annual meeting.

The conclusion is based on a large international study on how hormone receptor status impacts breast cancer outcomes in young women with germline BRCA pathological variants (PVs).

Overall, “hormone receptor positivity did not seem to have a strong positive prognostic value in young BRCA carriers” with early breast cancer, lead investigator Luca Arecco, MD, an oncology resident at the University of Genoa, Italy, said at the meeting.

Investigators reviewed the records of 4709 women ages 40 years or younger with stage 1-3 BRCA-associated invasive breast cancer treated from 2000 to 2020 at 78 centers in 28 countries across four continents. Median follow-up was about 8 years.
 

Weaker Prognostic Value in Hormone Receptor Status

They found, in general, that hormone receptor–positive breast cancer appears to be biologically more aggressive in patients with BRCA PVs than in the general breast cancer population, generating outcomes similar to those with hormone receptor-negative BRCA tumors.

Specifically, among patients with germline BRCA PVs, while hormone receptor–positive patients had a higher distant recurrence rate (13.1% vs. 9.6%) than hormone receptor–negative patients, 8-year disease free survival (65.8% and 63.4% respectively) and overall survival (a bit under 90% in both groups) were similar.

Hormone receptor–positive patients did have a lower rate of second primary breast cancers (9.1% versus 14.7%).

In the formal write-up of the results published shortly after the meeting in Annals of Oncology, the investigators concluded that “in young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor–positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.”

The team also found other differences between BRCA-associated breast cancer and sporadic disease. For instance, in the BRCA cohort, luminal A-like breast cancer had a worse long-term prognosis in their BRCA cohort than triple-negative or HER2-positive disease. Luminal A-like tumors are generally considered less aggressive, but in patients with BRCA PVs, “improving neoadjuvant chemotherapy … could be worthwhile,” the investigators said.

Also, although the risk of recurrence for sporadic hormone receptor–negative tumors is highest in the first few years, the team found that the risk in the hormone negative BRCA cohort progressively increased with longer follow-up, driven by the occurrence of second primary breast cancers, especially in patients with BRCA 1 PVs.
 

Greater Clarity in Prognosis in BRCA-Associated Breast Cancer

Overall, study discussant Lisa A. Carey, MD, a breast cancer specialist at the University of North Carolina at Chapel Hill, said, “we now know much more clearly the issues of prognosis in women who are very young and have germline BRCA-associated breast cancer,” about 12% of newly diagnosed cases.

“Young patients with germline BRCA-associated breast cancers have high relapse and high new primary risks, warranting comprehensive multimodality therapy,” she said.

A bit fewer than half of women in the study were hormone receptor–positive, and they tended to be patients with BRCA 2 PVs. The rest were hormone receptor–negative and tended to have BRCA 1 PVs.

Patients with hormone receptor–positive disease had grade 3 cancers in about 50% of cases, while patients with hormone receptor–negative disease had a grade 3 disease in over 80%.

Hormone receptor–positive patients were more likely to have nodal involvement and undergo mastectomies but less likely to receive chemotherapy than hormone receptor–negative patients. It’s likely that few patients in the review received PARP inhibitors, Dr. Carey noted.

Although overall survival at 8 years was similar in both groups, after that point “the prognosis of patients with hormone receptor–positive disease appeared to be worse … This appeared to occur earlier than that described in sporadic disease,” in which the worsening of survival in hormone receptor–positive disease occurs after a follow-up of at least 14-15 years, the investigators noted in their journal report.

The work was funded by the Italian Association for Cancer Research, Institut Jules Bordet, Korea Health Industry Development Institute, Australian National Health and Medical Council, Cancer Australia, US National Institute of Health, and others. Dr. Arecco had no disclosures. Dr. Carey and other coauthors disclosed research funding, speaker honoraria, and other financial relationships with AstraZeneca, Genentech/Roche, Lilly, and other pharmaceutical companies.

CHICAGO — Being hormone receptor positive is generally a favorable prognostic factor in breast cancer, but that doesn’t seem to be the case in women with BRCA-associated tumors, according to a study presented at the American Society of Clinical Oncology annual meeting.

The conclusion is based on a large international study on how hormone receptor status impacts breast cancer outcomes in young women with germline BRCA pathological variants (PVs).

Overall, “hormone receptor positivity did not seem to have a strong positive prognostic value in young BRCA carriers” with early breast cancer, lead investigator Luca Arecco, MD, an oncology resident at the University of Genoa, Italy, said at the meeting.

Investigators reviewed the records of 4709 women ages 40 years or younger with stage 1-3 BRCA-associated invasive breast cancer treated from 2000 to 2020 at 78 centers in 28 countries across four continents. Median follow-up was about 8 years.
 

Weaker Prognostic Value in Hormone Receptor Status

They found, in general, that hormone receptor–positive breast cancer appears to be biologically more aggressive in patients with BRCA PVs than in the general breast cancer population, generating outcomes similar to those with hormone receptor-negative BRCA tumors.

Specifically, among patients with germline BRCA PVs, while hormone receptor–positive patients had a higher distant recurrence rate (13.1% vs. 9.6%) than hormone receptor–negative patients, 8-year disease free survival (65.8% and 63.4% respectively) and overall survival (a bit under 90% in both groups) were similar.

Hormone receptor–positive patients did have a lower rate of second primary breast cancers (9.1% versus 14.7%).

In the formal write-up of the results published shortly after the meeting in Annals of Oncology, the investigators concluded that “in young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor–positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.”

The team also found other differences between BRCA-associated breast cancer and sporadic disease. For instance, in the BRCA cohort, luminal A-like breast cancer had a worse long-term prognosis in their BRCA cohort than triple-negative or HER2-positive disease. Luminal A-like tumors are generally considered less aggressive, but in patients with BRCA PVs, “improving neoadjuvant chemotherapy … could be worthwhile,” the investigators said.

Also, although the risk of recurrence for sporadic hormone receptor–negative tumors is highest in the first few years, the team found that the risk in the hormone negative BRCA cohort progressively increased with longer follow-up, driven by the occurrence of second primary breast cancers, especially in patients with BRCA 1 PVs.
 

Greater Clarity in Prognosis in BRCA-Associated Breast Cancer

Overall, study discussant Lisa A. Carey, MD, a breast cancer specialist at the University of North Carolina at Chapel Hill, said, “we now know much more clearly the issues of prognosis in women who are very young and have germline BRCA-associated breast cancer,” about 12% of newly diagnosed cases.

“Young patients with germline BRCA-associated breast cancers have high relapse and high new primary risks, warranting comprehensive multimodality therapy,” she said.

A bit fewer than half of women in the study were hormone receptor–positive, and they tended to be patients with BRCA 2 PVs. The rest were hormone receptor–negative and tended to have BRCA 1 PVs.

Patients with hormone receptor–positive disease had grade 3 cancers in about 50% of cases, while patients with hormone receptor–negative disease had a grade 3 disease in over 80%.

Hormone receptor–positive patients were more likely to have nodal involvement and undergo mastectomies but less likely to receive chemotherapy than hormone receptor–negative patients. It’s likely that few patients in the review received PARP inhibitors, Dr. Carey noted.

Although overall survival at 8 years was similar in both groups, after that point “the prognosis of patients with hormone receptor–positive disease appeared to be worse … This appeared to occur earlier than that described in sporadic disease,” in which the worsening of survival in hormone receptor–positive disease occurs after a follow-up of at least 14-15 years, the investigators noted in their journal report.

The work was funded by the Italian Association for Cancer Research, Institut Jules Bordet, Korea Health Industry Development Institute, Australian National Health and Medical Council, Cancer Australia, US National Institute of Health, and others. Dr. Arecco had no disclosures. Dr. Carey and other coauthors disclosed research funding, speaker honoraria, and other financial relationships with AstraZeneca, Genentech/Roche, Lilly, and other pharmaceutical companies.

CHICAGO — Being hormone receptor positive is generally a favorable prognostic factor in breast cancer, but that doesn’t seem to be the case in women with BRCA-associated tumors, according to a study presented at the American Society of Clinical Oncology annual meeting.

The conclusion is based on a large international study on how hormone receptor status impacts breast cancer outcomes in young women with germline BRCA pathological variants (PVs).

Overall, “hormone receptor positivity did not seem to have a strong positive prognostic value in young BRCA carriers” with early breast cancer, lead investigator Luca Arecco, MD, an oncology resident at the University of Genoa, Italy, said at the meeting.

Investigators reviewed the records of 4709 women ages 40 years or younger with stage 1-3 BRCA-associated invasive breast cancer treated from 2000 to 2020 at 78 centers in 28 countries across four continents. Median follow-up was about 8 years.
 

Weaker Prognostic Value in Hormone Receptor Status

They found, in general, that hormone receptor–positive breast cancer appears to be biologically more aggressive in patients with BRCA PVs than in the general breast cancer population, generating outcomes similar to those with hormone receptor-negative BRCA tumors.

Specifically, among patients with germline BRCA PVs, while hormone receptor–positive patients had a higher distant recurrence rate (13.1% vs. 9.6%) than hormone receptor–negative patients, 8-year disease free survival (65.8% and 63.4% respectively) and overall survival (a bit under 90% in both groups) were similar.

Hormone receptor–positive patients did have a lower rate of second primary breast cancers (9.1% versus 14.7%).

In the formal write-up of the results published shortly after the meeting in Annals of Oncology, the investigators concluded that “in young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor–positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.”

The team also found other differences between BRCA-associated breast cancer and sporadic disease. For instance, in the BRCA cohort, luminal A-like breast cancer had a worse long-term prognosis in their BRCA cohort than triple-negative or HER2-positive disease. Luminal A-like tumors are generally considered less aggressive, but in patients with BRCA PVs, “improving neoadjuvant chemotherapy … could be worthwhile,” the investigators said.

Also, although the risk of recurrence for sporadic hormone receptor–negative tumors is highest in the first few years, the team found that the risk in the hormone negative BRCA cohort progressively increased with longer follow-up, driven by the occurrence of second primary breast cancers, especially in patients with BRCA 1 PVs.
 

Greater Clarity in Prognosis in BRCA-Associated Breast Cancer

Overall, study discussant Lisa A. Carey, MD, a breast cancer specialist at the University of North Carolina at Chapel Hill, said, “we now know much more clearly the issues of prognosis in women who are very young and have germline BRCA-associated breast cancer,” about 12% of newly diagnosed cases.

“Young patients with germline BRCA-associated breast cancers have high relapse and high new primary risks, warranting comprehensive multimodality therapy,” she said.

A bit fewer than half of women in the study were hormone receptor–positive, and they tended to be patients with BRCA 2 PVs. The rest were hormone receptor–negative and tended to have BRCA 1 PVs.

Patients with hormone receptor–positive disease had grade 3 cancers in about 50% of cases, while patients with hormone receptor–negative disease had a grade 3 disease in over 80%.

Hormone receptor–positive patients were more likely to have nodal involvement and undergo mastectomies but less likely to receive chemotherapy than hormone receptor–negative patients. It’s likely that few patients in the review received PARP inhibitors, Dr. Carey noted.

Although overall survival at 8 years was similar in both groups, after that point “the prognosis of patients with hormone receptor–positive disease appeared to be worse … This appeared to occur earlier than that described in sporadic disease,” in which the worsening of survival in hormone receptor–positive disease occurs after a follow-up of at least 14-15 years, the investigators noted in their journal report.

The work was funded by the Italian Association for Cancer Research, Institut Jules Bordet, Korea Health Industry Development Institute, Australian National Health and Medical Council, Cancer Australia, US National Institute of Health, and others. Dr. Arecco had no disclosures. Dr. Carey and other coauthors disclosed research funding, speaker honoraria, and other financial relationships with AstraZeneca, Genentech/Roche, Lilly, and other pharmaceutical companies.

Black metastatic breast cancer patients with PIK3CA mutations were less likely to receive targeted therapy and less likely to be enrolled in clinical trials than White patients and had shorter overall survival, according to a retrospective cohort study. Black and White patients were equally likely to receive other drugs that did not require genomic testing.

“These clinical inequities in the use of targeted therapies and clinical trials ... must be a focus going forward,” said lead investigator Emily Podany, MD, a clinical fellow in hematology-oncology at Washington University in St. Louis, Missouri. “Our consortium is looking for paths forward in order to try and decrease these striking inequities. And it’s a focus of future research for us and future implementation [of] science interventions, hopefully, across the country.”

The study results were presented at the annual meeting of the American Society of Clinical Oncology.
 

Black Women Underrepresented

Black women are generally underrepresented in clinical trials, noted Dr. Podany. “They make up about 2%-5% of the patients in breast cancer clinical trials, and there are documented inequities in treatment and in outcomes for Black patients with metastatic breast cancer. This includes longer treatment delays, it includes fewer sentinel lymph node biopsies, and unfortunately, they’re more likely to discontinue treatment early.”

In terms of PI3K inhibition, PIK3CA mutations are found in about 40% of patients with HR-positive HER2-negative metastatic breast cancer. Alpelisib is FDA-approved as a targeted therapy for these patients, she said.

The study evaluated records of 1327 patients with metastatic breast cancer who also had circulating tumor DNA (ctDNA) results and were treated at Washington University, Massachusetts General Hospital in Boston, and Northwestern University in Chicago. Of these, 795 had an ER-positive, HER2-negative subtype and were included in the analysis. Most (89%) of the patients were White (n = 708), while 11% (n = 87) were Black, and the only baseline difference between patients was that Black patients had significantly more de novo metastatic breast cancer (31% versus 22%).

Use of PI3K, CDK4/6, or mTOR inhibitors was evaluated using manual electronic medical review, and genomic differences were evaluated using logistic regression.

The analysis showed inequities in both treatment and clinical trial enrollment. There were no differences between groups in the use of CDK4/6 or mTOR inhibitors, which do not require a genomic profile, the researchers noted, but Black patients with PIK3CA single nucleotide variants (SNV) were significantly less likely than White patients to use PI3K inhibitors (5.9% versus 28.8%; P = .045), despite no difference in PIK3CA mutations between groups (36% and 34% respectively). Similarly, 11% of White patients with PIK3CA mutations were enrolled in clinical trials, but none of the Black patients was.

Genomic differences were also found, Dr. Podany reported. Black patients with estrogen/progesterone receptor (ER/PR) positive, HER2-negative disease were more likely to have a CCND1 copy number variant. And for ER-positive PR-negative HER2-negative patients, Black patients were more likely to have a GATA3 SNV, while White patients were more likely to have a KRAS copy number variant.
 

Black Survival Less Than Half

The analysis also found significant differences in overall survival from the time of the first liquid biopsy, with White ER-positive, PR-negative, HER2-negative patients living a median of 21 months, versus 9.1 months for Black patients.

There were several limitations to the study beyond its retrospective nature, “so, we may be underestimating the true inequity,” noted Dr. Podany. “These are large urban academic centers, so our patients have access to these treatments. They have access to care. They have access to ctDNA liquid biopsy testing. And the timing of ctDNA, especially the first ctDNA test, is variable and provider-dependant. We were also unable to assess receipt of PI3 kinase inhibitors at future time points after the end of this cohort study.”

Asked for comment, Giuseppe Del Priore, MD, MPH, from Morehouse School of Medicine in Atlanta, Georgia, approved of the study design “with subjects limited to three distinctive institutions. That parameter alone can control for several unknown variables among the studied comparison groups, ie, Black women versus others.”

However, Dr. Del Priore, who is adjunct professor of obstetrics and gynecology, with a specialty in oncology, added, “retrospective studies are not reliable except for generating hypotheses. Therefore, I would like to see a rapid implementation of an intervention trial at these same institutions to ensure equal consideration of, and access to, targeted therapies. Too often a retrospective correlation is reported, but the solution is elusive due to unknown factors. In this case, knowing there is a mutation is far from alleviating the disproportionate burden of disease that many communities face.”

Dr. Podany had no relevant disclosures. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

Black metastatic breast cancer patients with PIK3CA mutations were less likely to receive targeted therapy and less likely to be enrolled in clinical trials than White patients and had shorter overall survival, according to a retrospective cohort study. Black and White patients were equally likely to receive other drugs that did not require genomic testing.

“These clinical inequities in the use of targeted therapies and clinical trials ... must be a focus going forward,” said lead investigator Emily Podany, MD, a clinical fellow in hematology-oncology at Washington University in St. Louis, Missouri. “Our consortium is looking for paths forward in order to try and decrease these striking inequities. And it’s a focus of future research for us and future implementation [of] science interventions, hopefully, across the country.”

The study results were presented at the annual meeting of the American Society of Clinical Oncology.
 

Black Women Underrepresented

Black women are generally underrepresented in clinical trials, noted Dr. Podany. “They make up about 2%-5% of the patients in breast cancer clinical trials, and there are documented inequities in treatment and in outcomes for Black patients with metastatic breast cancer. This includes longer treatment delays, it includes fewer sentinel lymph node biopsies, and unfortunately, they’re more likely to discontinue treatment early.”

In terms of PI3K inhibition, PIK3CA mutations are found in about 40% of patients with HR-positive HER2-negative metastatic breast cancer. Alpelisib is FDA-approved as a targeted therapy for these patients, she said.

The study evaluated records of 1327 patients with metastatic breast cancer who also had circulating tumor DNA (ctDNA) results and were treated at Washington University, Massachusetts General Hospital in Boston, and Northwestern University in Chicago. Of these, 795 had an ER-positive, HER2-negative subtype and were included in the analysis. Most (89%) of the patients were White (n = 708), while 11% (n = 87) were Black, and the only baseline difference between patients was that Black patients had significantly more de novo metastatic breast cancer (31% versus 22%).

Use of PI3K, CDK4/6, or mTOR inhibitors was evaluated using manual electronic medical review, and genomic differences were evaluated using logistic regression.

The analysis showed inequities in both treatment and clinical trial enrollment. There were no differences between groups in the use of CDK4/6 or mTOR inhibitors, which do not require a genomic profile, the researchers noted, but Black patients with PIK3CA single nucleotide variants (SNV) were significantly less likely than White patients to use PI3K inhibitors (5.9% versus 28.8%; P = .045), despite no difference in PIK3CA mutations between groups (36% and 34% respectively). Similarly, 11% of White patients with PIK3CA mutations were enrolled in clinical trials, but none of the Black patients was.

Genomic differences were also found, Dr. Podany reported. Black patients with estrogen/progesterone receptor (ER/PR) positive, HER2-negative disease were more likely to have a CCND1 copy number variant. And for ER-positive PR-negative HER2-negative patients, Black patients were more likely to have a GATA3 SNV, while White patients were more likely to have a KRAS copy number variant.
 

Black Survival Less Than Half

The analysis also found significant differences in overall survival from the time of the first liquid biopsy, with White ER-positive, PR-negative, HER2-negative patients living a median of 21 months, versus 9.1 months for Black patients.

There were several limitations to the study beyond its retrospective nature, “so, we may be underestimating the true inequity,” noted Dr. Podany. “These are large urban academic centers, so our patients have access to these treatments. They have access to care. They have access to ctDNA liquid biopsy testing. And the timing of ctDNA, especially the first ctDNA test, is variable and provider-dependant. We were also unable to assess receipt of PI3 kinase inhibitors at future time points after the end of this cohort study.”

Asked for comment, Giuseppe Del Priore, MD, MPH, from Morehouse School of Medicine in Atlanta, Georgia, approved of the study design “with subjects limited to three distinctive institutions. That parameter alone can control for several unknown variables among the studied comparison groups, ie, Black women versus others.”

However, Dr. Del Priore, who is adjunct professor of obstetrics and gynecology, with a specialty in oncology, added, “retrospective studies are not reliable except for generating hypotheses. Therefore, I would like to see a rapid implementation of an intervention trial at these same institutions to ensure equal consideration of, and access to, targeted therapies. Too often a retrospective correlation is reported, but the solution is elusive due to unknown factors. In this case, knowing there is a mutation is far from alleviating the disproportionate burden of disease that many communities face.”

Dr. Podany had no relevant disclosures. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

Black metastatic breast cancer patients with PIK3CA mutations were less likely to receive targeted therapy and less likely to be enrolled in clinical trials than White patients and had shorter overall survival, according to a retrospective cohort study. Black and White patients were equally likely to receive other drugs that did not require genomic testing.

“These clinical inequities in the use of targeted therapies and clinical trials ... must be a focus going forward,” said lead investigator Emily Podany, MD, a clinical fellow in hematology-oncology at Washington University in St. Louis, Missouri. “Our consortium is looking for paths forward in order to try and decrease these striking inequities. And it’s a focus of future research for us and future implementation [of] science interventions, hopefully, across the country.”

The study results were presented at the annual meeting of the American Society of Clinical Oncology.
 

Black Women Underrepresented

Black women are generally underrepresented in clinical trials, noted Dr. Podany. “They make up about 2%-5% of the patients in breast cancer clinical trials, and there are documented inequities in treatment and in outcomes for Black patients with metastatic breast cancer. This includes longer treatment delays, it includes fewer sentinel lymph node biopsies, and unfortunately, they’re more likely to discontinue treatment early.”

In terms of PI3K inhibition, PIK3CA mutations are found in about 40% of patients with HR-positive HER2-negative metastatic breast cancer. Alpelisib is FDA-approved as a targeted therapy for these patients, she said.

The study evaluated records of 1327 patients with metastatic breast cancer who also had circulating tumor DNA (ctDNA) results and were treated at Washington University, Massachusetts General Hospital in Boston, and Northwestern University in Chicago. Of these, 795 had an ER-positive, HER2-negative subtype and were included in the analysis. Most (89%) of the patients were White (n = 708), while 11% (n = 87) were Black, and the only baseline difference between patients was that Black patients had significantly more de novo metastatic breast cancer (31% versus 22%).

Use of PI3K, CDK4/6, or mTOR inhibitors was evaluated using manual electronic medical review, and genomic differences were evaluated using logistic regression.

The analysis showed inequities in both treatment and clinical trial enrollment. There were no differences between groups in the use of CDK4/6 or mTOR inhibitors, which do not require a genomic profile, the researchers noted, but Black patients with PIK3CA single nucleotide variants (SNV) were significantly less likely than White patients to use PI3K inhibitors (5.9% versus 28.8%; P = .045), despite no difference in PIK3CA mutations between groups (36% and 34% respectively). Similarly, 11% of White patients with PIK3CA mutations were enrolled in clinical trials, but none of the Black patients was.

Genomic differences were also found, Dr. Podany reported. Black patients with estrogen/progesterone receptor (ER/PR) positive, HER2-negative disease were more likely to have a CCND1 copy number variant. And for ER-positive PR-negative HER2-negative patients, Black patients were more likely to have a GATA3 SNV, while White patients were more likely to have a KRAS copy number variant.
 

Black Survival Less Than Half

The analysis also found significant differences in overall survival from the time of the first liquid biopsy, with White ER-positive, PR-negative, HER2-negative patients living a median of 21 months, versus 9.1 months for Black patients.

There were several limitations to the study beyond its retrospective nature, “so, we may be underestimating the true inequity,” noted Dr. Podany. “These are large urban academic centers, so our patients have access to these treatments. They have access to care. They have access to ctDNA liquid biopsy testing. And the timing of ctDNA, especially the first ctDNA test, is variable and provider-dependant. We were also unable to assess receipt of PI3 kinase inhibitors at future time points after the end of this cohort study.”

Asked for comment, Giuseppe Del Priore, MD, MPH, from Morehouse School of Medicine in Atlanta, Georgia, approved of the study design “with subjects limited to three distinctive institutions. That parameter alone can control for several unknown variables among the studied comparison groups, ie, Black women versus others.”

However, Dr. Del Priore, who is adjunct professor of obstetrics and gynecology, with a specialty in oncology, added, “retrospective studies are not reliable except for generating hypotheses. Therefore, I would like to see a rapid implementation of an intervention trial at these same institutions to ensure equal consideration of, and access to, targeted therapies. Too often a retrospective correlation is reported, but the solution is elusive due to unknown factors. In this case, knowing there is a mutation is far from alleviating the disproportionate burden of disease that many communities face.”

Dr. Podany had no relevant disclosures. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.