AVAHO

Artera, the Los Altos, California–based developer of tools to diagnose cancer, has launched the first artificial intelligence (AI) test to guide patients in making informed decisions between active surveillance and active treatment based on an analysis of digital pathology images.

Trevor Royce, MD, MPH, senior medical director of Artera, said the new version of the ArteraAI Prostate Test helps patients with low-risk (Grade Group 1/Gleason 6) to favorable intermediate-risk (Grade Group 2/Gleason 3+4) prostate cancer choose between treatment or active surveillance.

The test estimates how a patient’s cancer may progress and predicts the benefit of treatment for localized prostate cancer. 

“The prognostic performance of the test has now been validated in a diverse cohort of patients, including those who have undergone active surveillance, radiation therapy, or had a radical prostatectomy,” said Dr. Royce, a faculty member in radiation oncology at Wake Forest University School of Medicine in Winston-Salem, North Carolina. “The prognostic risk result reflects the patient’s prognosis regardless of the treatment path chosen.”

Dr. Royce said the new test predicts the risk for developing distant metastasis in 10 years. For the population considering active surveillance, it also can predict the likelihood their cancer will show more aggressive features. The test does not make a clinical recommendation, he added.

“Ultimately, that’s a very personal decision between the patient and their physician, and we view it as supporting that decision-making process,” he said.

The test is available in all states but New York and California, where the company is now, in discussions with regulators for approval, according to Dr. Royce. He said the company is in discussion with private insurers to set reimbursement and payment rates. In January 2024, Medicare set a payment rate of $700 for the AI test, which carries no out-of-pocket costs for patients. 

The first indication for the test was for localized prostate cancer, prognosticating the risk for distant metastases and death from prostate cancer. It can also predict if an individual will benefit from androgen deprivation therapy (ADT). Dr. Royce said up to 60% of patients with intermediate risk prostate cancer now can avoid ADT and its serious side effects, such as brain fog, weight gain, and reduction in muscle mass.

In March, the National Comprehensive Cancer Network, an alliance of 33 cancer centers included Artera as the first AI test in its Clinical Practice Guidelines in Oncology.

Dr. Royce said active surveillance is a new application of the test. The test was initially developed on a foundational study of almost 22,000 pathology slides from nearly 7000 patients published in npj Digital Medicine in 2022.

Todd Morgan, MD, chief of the Division of Urologic Oncology at the University of Michigan in Ann Arbor, and coauthor of the foundational study, said the AI test adds another layer of data to making clinical decisions for lower-risk patients.

“The technology is a big deal. The ability to use digital images to make accurate prognostic estimates is pretty remarkable, and this is the first test in any disease site to do this,” Dr. Morgan said. “Ultimately, this means tests may someday be performed by just sending images rather than sending actual tissue to an outside laboratory. Is the AI test dramatically more accurate than the genomic platforms? That’s TBD [to be determined].”

Dr. Royce said Artera is now working on a version of its test to inform men with higher-risk prostate cancer how long ADT should last and what the prognosis is for patients who have undergone prostatectomy based on their surgical specimen. The current test uses samples from the prostate biopsy, which are processed in a central lab. 

Dr. Royce said the company would like to eventually perform the test using digital images of pathology slides only.

Dr. Morgan reported no conflicts of interest.
 

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

Artera, the Los Altos, California–based developer of tools to diagnose cancer, has launched the first artificial intelligence (AI) test to guide patients in making informed decisions between active surveillance and active treatment based on an analysis of digital pathology images.

Trevor Royce, MD, MPH, senior medical director of Artera, said the new version of the ArteraAI Prostate Test helps patients with low-risk (Grade Group 1/Gleason 6) to favorable intermediate-risk (Grade Group 2/Gleason 3+4) prostate cancer choose between treatment or active surveillance.

The test estimates how a patient’s cancer may progress and predicts the benefit of treatment for localized prostate cancer. 

“The prognostic performance of the test has now been validated in a diverse cohort of patients, including those who have undergone active surveillance, radiation therapy, or had a radical prostatectomy,” said Dr. Royce, a faculty member in radiation oncology at Wake Forest University School of Medicine in Winston-Salem, North Carolina. “The prognostic risk result reflects the patient’s prognosis regardless of the treatment path chosen.”

Dr. Royce said the new test predicts the risk for developing distant metastasis in 10 years. For the population considering active surveillance, it also can predict the likelihood their cancer will show more aggressive features. The test does not make a clinical recommendation, he added.

“Ultimately, that’s a very personal decision between the patient and their physician, and we view it as supporting that decision-making process,” he said.

The test is available in all states but New York and California, where the company is now, in discussions with regulators for approval, according to Dr. Royce. He said the company is in discussion with private insurers to set reimbursement and payment rates. In January 2024, Medicare set a payment rate of $700 for the AI test, which carries no out-of-pocket costs for patients. 

The first indication for the test was for localized prostate cancer, prognosticating the risk for distant metastases and death from prostate cancer. It can also predict if an individual will benefit from androgen deprivation therapy (ADT). Dr. Royce said up to 60% of patients with intermediate risk prostate cancer now can avoid ADT and its serious side effects, such as brain fog, weight gain, and reduction in muscle mass.

In March, the National Comprehensive Cancer Network, an alliance of 33 cancer centers included Artera as the first AI test in its Clinical Practice Guidelines in Oncology.

Dr. Royce said active surveillance is a new application of the test. The test was initially developed on a foundational study of almost 22,000 pathology slides from nearly 7000 patients published in npj Digital Medicine in 2022.

Todd Morgan, MD, chief of the Division of Urologic Oncology at the University of Michigan in Ann Arbor, and coauthor of the foundational study, said the AI test adds another layer of data to making clinical decisions for lower-risk patients.

“The technology is a big deal. The ability to use digital images to make accurate prognostic estimates is pretty remarkable, and this is the first test in any disease site to do this,” Dr. Morgan said. “Ultimately, this means tests may someday be performed by just sending images rather than sending actual tissue to an outside laboratory. Is the AI test dramatically more accurate than the genomic platforms? That’s TBD [to be determined].”

Dr. Royce said Artera is now working on a version of its test to inform men with higher-risk prostate cancer how long ADT should last and what the prognosis is for patients who have undergone prostatectomy based on their surgical specimen. The current test uses samples from the prostate biopsy, which are processed in a central lab. 

Dr. Royce said the company would like to eventually perform the test using digital images of pathology slides only.

Dr. Morgan reported no conflicts of interest.
 

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

Artera, the Los Altos, California–based developer of tools to diagnose cancer, has launched the first artificial intelligence (AI) test to guide patients in making informed decisions between active surveillance and active treatment based on an analysis of digital pathology images.

Trevor Royce, MD, MPH, senior medical director of Artera, said the new version of the ArteraAI Prostate Test helps patients with low-risk (Grade Group 1/Gleason 6) to favorable intermediate-risk (Grade Group 2/Gleason 3+4) prostate cancer choose between treatment or active surveillance.

The test estimates how a patient’s cancer may progress and predicts the benefit of treatment for localized prostate cancer. 

“The prognostic performance of the test has now been validated in a diverse cohort of patients, including those who have undergone active surveillance, radiation therapy, or had a radical prostatectomy,” said Dr. Royce, a faculty member in radiation oncology at Wake Forest University School of Medicine in Winston-Salem, North Carolina. “The prognostic risk result reflects the patient’s prognosis regardless of the treatment path chosen.”

Dr. Royce said the new test predicts the risk for developing distant metastasis in 10 years. For the population considering active surveillance, it also can predict the likelihood their cancer will show more aggressive features. The test does not make a clinical recommendation, he added.

“Ultimately, that’s a very personal decision between the patient and their physician, and we view it as supporting that decision-making process,” he said.

The test is available in all states but New York and California, where the company is now, in discussions with regulators for approval, according to Dr. Royce. He said the company is in discussion with private insurers to set reimbursement and payment rates. In January 2024, Medicare set a payment rate of $700 for the AI test, which carries no out-of-pocket costs for patients. 

The first indication for the test was for localized prostate cancer, prognosticating the risk for distant metastases and death from prostate cancer. It can also predict if an individual will benefit from androgen deprivation therapy (ADT). Dr. Royce said up to 60% of patients with intermediate risk prostate cancer now can avoid ADT and its serious side effects, such as brain fog, weight gain, and reduction in muscle mass.

In March, the National Comprehensive Cancer Network, an alliance of 33 cancer centers included Artera as the first AI test in its Clinical Practice Guidelines in Oncology.

Dr. Royce said active surveillance is a new application of the test. The test was initially developed on a foundational study of almost 22,000 pathology slides from nearly 7000 patients published in npj Digital Medicine in 2022.

Todd Morgan, MD, chief of the Division of Urologic Oncology at the University of Michigan in Ann Arbor, and coauthor of the foundational study, said the AI test adds another layer of data to making clinical decisions for lower-risk patients.

“The technology is a big deal. The ability to use digital images to make accurate prognostic estimates is pretty remarkable, and this is the first test in any disease site to do this,” Dr. Morgan said. “Ultimately, this means tests may someday be performed by just sending images rather than sending actual tissue to an outside laboratory. Is the AI test dramatically more accurate than the genomic platforms? That’s TBD [to be determined].”

Dr. Royce said Artera is now working on a version of its test to inform men with higher-risk prostate cancer how long ADT should last and what the prognosis is for patients who have undergone prostatectomy based on their surgical specimen. The current test uses samples from the prostate biopsy, which are processed in a central lab. 

Dr. Royce said the company would like to eventually perform the test using digital images of pathology slides only.

Dr. Morgan reported no conflicts of interest.
 

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

TOPLINE:

An easy-to-use web-based prognostic tool, MetroPancreas, may help predict the likelihood of futile pancreatectomy in patients with resectable pancreatic ductal adenocarcinoma and improve patient selection for upfront surgery.

METHODOLOGY:

• Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
• To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
• The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
• The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
• The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.

TAKEAWAY:

• The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
• Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
• The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
• Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).

IN PRACTICE:

“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.

SOURCE:

This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.

LIMITATIONS:

In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.

DISCLOSURES:

The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.

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

TOPLINE:

An easy-to-use web-based prognostic tool, MetroPancreas, may help predict the likelihood of futile pancreatectomy in patients with resectable pancreatic ductal adenocarcinoma and improve patient selection for upfront surgery.

METHODOLOGY:

• Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
• To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
• The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
• The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
• The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.

TAKEAWAY:

• The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
• Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
• The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
• Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).

IN PRACTICE:

“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.

SOURCE:

This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.

LIMITATIONS:

In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.

DISCLOSURES:

The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.

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

TOPLINE:

An easy-to-use web-based prognostic tool, MetroPancreas, may help predict the likelihood of futile pancreatectomy in patients with resectable pancreatic ductal adenocarcinoma and improve patient selection for upfront surgery.

METHODOLOGY:

• Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
• To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
• The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
• The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
• The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.

TAKEAWAY:

• The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
• Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
• The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
• Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).

IN PRACTICE:

“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.

SOURCE:

This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.

LIMITATIONS:

In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.

DISCLOSURES:

The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.

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 lowest point in the nascent career of Neelendu Dey, MD, helped seal his fate as a physician-scientist.

He had just started his first year as a resident at University of California, San Francisco. One of his patients was a 30-year-old woman who was dying of metastatic colorectal cancer. “I was in my mid-20s interacting with an individual just a few years older than I am, going through one of the most terrible health outcomes one could imagine,” Dr. Dey said.

He remembers asking the patient what he could do for her, how he could make her feel more comfortable. “That feeling of helplessness, particularly as we think about young people developing cancer, it really stuck with me through the years,” he said.

Dr. Dey, a graduate of the AGA Future Leaders Program, is now a gastroenterologist and researcher at the Fred Hutch Cancer Center in Seattle. In an interview, he talked about his dual role as a physician and scientist, and how those two interests are guiding his research in precancerous conditions of the colon.

Cases like that of the young woman with colon cancer “really help drive the urgency of the work we do, and the research questions we ask, as we try to move the ball forward and help folks at earlier stages,” he said.

Fred Hutch Cancer Center

Q: Why did you choose GI?

When you think about what sorts of chronic diseases really impact your quality of life, gut health is one of the chief contributors among various aspects of health. And that really appealed to me — the ability to take someone who is essentially handicapped by a series of illnesses and symptoms that derive from the GI tract and enable them to return to the person they want to be, to be productive in the way that they want to be, and have a rewarding life.

As I thought about how I wanted to contribute to the future of medicine, one of the ways in which I’ve always thought that I would do that is through research. When I considered the fields that really appealed to me, both from that clinical standpoint and research standpoint, GI was one that really stood out. There has been a lot of exciting research going on in GI. My lab currently studies the microbiome, and I feel like this is an area in which we can contribute.
 

Q: What role does digestive health play in overall health?

Obviously, the direct answer is gut health is so critical in something like nutritional intake. Some GI symptoms, if your gut health has gone awry, can really be detrimental in terms of quality of life. But one less obvious role that digestive health plays is its long-term effects. We’re starting to appreciate that gut health, the gut microbiome, and gut immune education are probably long-term players. Some experiences in early life might shape our immunity in ways that have consequences for us much later in life. Whether we get early life antibiotics, for example, may potentially contribute to colorectal cancer down the line. Thinking about the long-term players is more challenging, but it’s also an appealing opportunity as we think about how we can shape medicine moving forward.

Q: What practice challenges have you faced in your career?

First, being a physician-scientist. It’s challenging to be either a physician alone or to be a researcher alone. And trying to do both includes the challenges of both individual worlds. It just takes more time to get all the prerequisite training. And second, there are just challenges with getting the opportunities to contribute in the ways that you want — to get the research funding, to get the papers out, things like that.

Q: Tell me about the work you’ve been doing in your lab to develop microbiome-based strategies for preventing and treating cancer.

The microbiome presents several opportunities when it comes to cancer prevention. One is identifying markers of cancer risk, or of general good health down the line. Some of those biomarkers could — potentially — feed directly into personalized risk assessment and maybe even inform a future screening strategy. The second opportunity the microbiome presents is if we identify a microbe that influences your cancer risk, can we then understand and exploit, or utilize, that mechanism to mitigate cancer risk in the future? Our lab has done work looking at subspecies levels of microbes that track with health or cancer. We’ve done some work to identify what these subspecies groupings are and have identified some links to certain precancerous changes in the colon. We think that there’s an opportunity here for future interventions.

Q: Have you published other papers?

We recently published another paper describing how some microbes can interact with a tumor suppressor gene and are influenced in a sex-biased manner to drive tumorigenesis in a mouse model. We think, based on what we’re seeing in human data, that there may be some relationships and we’re exploring that now as well. 

Q: What is your vision for the future in GI, and in your career?

The vision that I have is to create clinical tools that can expand our reach and our effectiveness and cancer prevention. I think that there are opportunities for leveraging microbiome research to accomplish this. And one outcome I could imagine is leveraging some of these insights to expand noninvasive screening at even earlier ages than we do now. I mean, we just dialed back the recommended age for colonoscopy for average risk individuals to 45. But I could envision a future in which noninvasive screening starts earlier, in which the first stool-based tests that we deploy to assess personalized risk are used in the pediatric clinic.

Lightning Round

Texting or talking?

Talking

Favorite city in the United States besides the one you live in?

St. Louis

Cat or dog person?

Both

If you weren’t a GI, what would you be?

Musician

Best place you went on vacation?

Borneo

Favorite sport?

Soccer

Favorite ice cream?

Cashew-based salted caramel

What song do you have to sing along with when you hear it?

Sweet Child of Mine

Favorite movie or TV show?

25th Hour or Shawshank Redemption

Optimist or Pessimist?

Optimist

The lowest point in the nascent career of Neelendu Dey, MD, helped seal his fate as a physician-scientist.

He had just started his first year as a resident at University of California, San Francisco. One of his patients was a 30-year-old woman who was dying of metastatic colorectal cancer. “I was in my mid-20s interacting with an individual just a few years older than I am, going through one of the most terrible health outcomes one could imagine,” Dr. Dey said.

He remembers asking the patient what he could do for her, how he could make her feel more comfortable. “That feeling of helplessness, particularly as we think about young people developing cancer, it really stuck with me through the years,” he said.

Dr. Dey, a graduate of the AGA Future Leaders Program, is now a gastroenterologist and researcher at the Fred Hutch Cancer Center in Seattle. In an interview, he talked about his dual role as a physician and scientist, and how those two interests are guiding his research in precancerous conditions of the colon.

Cases like that of the young woman with colon cancer “really help drive the urgency of the work we do, and the research questions we ask, as we try to move the ball forward and help folks at earlier stages,” he said.

Fred Hutch Cancer Center

Q: Why did you choose GI?

When you think about what sorts of chronic diseases really impact your quality of life, gut health is one of the chief contributors among various aspects of health. And that really appealed to me — the ability to take someone who is essentially handicapped by a series of illnesses and symptoms that derive from the GI tract and enable them to return to the person they want to be, to be productive in the way that they want to be, and have a rewarding life.

As I thought about how I wanted to contribute to the future of medicine, one of the ways in which I’ve always thought that I would do that is through research. When I considered the fields that really appealed to me, both from that clinical standpoint and research standpoint, GI was one that really stood out. There has been a lot of exciting research going on in GI. My lab currently studies the microbiome, and I feel like this is an area in which we can contribute.
 

Q: What role does digestive health play in overall health?

Obviously, the direct answer is gut health is so critical in something like nutritional intake. Some GI symptoms, if your gut health has gone awry, can really be detrimental in terms of quality of life. But one less obvious role that digestive health plays is its long-term effects. We’re starting to appreciate that gut health, the gut microbiome, and gut immune education are probably long-term players. Some experiences in early life might shape our immunity in ways that have consequences for us much later in life. Whether we get early life antibiotics, for example, may potentially contribute to colorectal cancer down the line. Thinking about the long-term players is more challenging, but it’s also an appealing opportunity as we think about how we can shape medicine moving forward.

Q: What practice challenges have you faced in your career?

First, being a physician-scientist. It’s challenging to be either a physician alone or to be a researcher alone. And trying to do both includes the challenges of both individual worlds. It just takes more time to get all the prerequisite training. And second, there are just challenges with getting the opportunities to contribute in the ways that you want — to get the research funding, to get the papers out, things like that.

Q: Tell me about the work you’ve been doing in your lab to develop microbiome-based strategies for preventing and treating cancer.

The microbiome presents several opportunities when it comes to cancer prevention. One is identifying markers of cancer risk, or of general good health down the line. Some of those biomarkers could — potentially — feed directly into personalized risk assessment and maybe even inform a future screening strategy. The second opportunity the microbiome presents is if we identify a microbe that influences your cancer risk, can we then understand and exploit, or utilize, that mechanism to mitigate cancer risk in the future? Our lab has done work looking at subspecies levels of microbes that track with health or cancer. We’ve done some work to identify what these subspecies groupings are and have identified some links to certain precancerous changes in the colon. We think that there’s an opportunity here for future interventions.

Q: Have you published other papers?

We recently published another paper describing how some microbes can interact with a tumor suppressor gene and are influenced in a sex-biased manner to drive tumorigenesis in a mouse model. We think, based on what we’re seeing in human data, that there may be some relationships and we’re exploring that now as well. 

Q: What is your vision for the future in GI, and in your career?

The vision that I have is to create clinical tools that can expand our reach and our effectiveness and cancer prevention. I think that there are opportunities for leveraging microbiome research to accomplish this. And one outcome I could imagine is leveraging some of these insights to expand noninvasive screening at even earlier ages than we do now. I mean, we just dialed back the recommended age for colonoscopy for average risk individuals to 45. But I could envision a future in which noninvasive screening starts earlier, in which the first stool-based tests that we deploy to assess personalized risk are used in the pediatric clinic.

Lightning Round

Texting or talking?

Talking

Favorite city in the United States besides the one you live in?

St. Louis

Cat or dog person?

Both

If you weren’t a GI, what would you be?

Musician

Best place you went on vacation?

Borneo

Favorite sport?

Soccer

Favorite ice cream?

Cashew-based salted caramel

What song do you have to sing along with when you hear it?

Sweet Child of Mine

Favorite movie or TV show?

25th Hour or Shawshank Redemption

Optimist or Pessimist?

Optimist

The lowest point in the nascent career of Neelendu Dey, MD, helped seal his fate as a physician-scientist.

He had just started his first year as a resident at University of California, San Francisco. One of his patients was a 30-year-old woman who was dying of metastatic colorectal cancer. “I was in my mid-20s interacting with an individual just a few years older than I am, going through one of the most terrible health outcomes one could imagine,” Dr. Dey said.

He remembers asking the patient what he could do for her, how he could make her feel more comfortable. “That feeling of helplessness, particularly as we think about young people developing cancer, it really stuck with me through the years,” he said.

Dr. Dey, a graduate of the AGA Future Leaders Program, is now a gastroenterologist and researcher at the Fred Hutch Cancer Center in Seattle. In an interview, he talked about his dual role as a physician and scientist, and how those two interests are guiding his research in precancerous conditions of the colon.

Cases like that of the young woman with colon cancer “really help drive the urgency of the work we do, and the research questions we ask, as we try to move the ball forward and help folks at earlier stages,” he said.

Fred Hutch Cancer Center

Q: Why did you choose GI?

When you think about what sorts of chronic diseases really impact your quality of life, gut health is one of the chief contributors among various aspects of health. And that really appealed to me — the ability to take someone who is essentially handicapped by a series of illnesses and symptoms that derive from the GI tract and enable them to return to the person they want to be, to be productive in the way that they want to be, and have a rewarding life.

As I thought about how I wanted to contribute to the future of medicine, one of the ways in which I’ve always thought that I would do that is through research. When I considered the fields that really appealed to me, both from that clinical standpoint and research standpoint, GI was one that really stood out. There has been a lot of exciting research going on in GI. My lab currently studies the microbiome, and I feel like this is an area in which we can contribute.
 

Q: What role does digestive health play in overall health?

Obviously, the direct answer is gut health is so critical in something like nutritional intake. Some GI symptoms, if your gut health has gone awry, can really be detrimental in terms of quality of life. But one less obvious role that digestive health plays is its long-term effects. We’re starting to appreciate that gut health, the gut microbiome, and gut immune education are probably long-term players. Some experiences in early life might shape our immunity in ways that have consequences for us much later in life. Whether we get early life antibiotics, for example, may potentially contribute to colorectal cancer down the line. Thinking about the long-term players is more challenging, but it’s also an appealing opportunity as we think about how we can shape medicine moving forward.

Q: What practice challenges have you faced in your career?

First, being a physician-scientist. It’s challenging to be either a physician alone or to be a researcher alone. And trying to do both includes the challenges of both individual worlds. It just takes more time to get all the prerequisite training. And second, there are just challenges with getting the opportunities to contribute in the ways that you want — to get the research funding, to get the papers out, things like that.

Q: Tell me about the work you’ve been doing in your lab to develop microbiome-based strategies for preventing and treating cancer.

The microbiome presents several opportunities when it comes to cancer prevention. One is identifying markers of cancer risk, or of general good health down the line. Some of those biomarkers could — potentially — feed directly into personalized risk assessment and maybe even inform a future screening strategy. The second opportunity the microbiome presents is if we identify a microbe that influences your cancer risk, can we then understand and exploit, or utilize, that mechanism to mitigate cancer risk in the future? Our lab has done work looking at subspecies levels of microbes that track with health or cancer. We’ve done some work to identify what these subspecies groupings are and have identified some links to certain precancerous changes in the colon. We think that there’s an opportunity here for future interventions.

Q: Have you published other papers?

We recently published another paper describing how some microbes can interact with a tumor suppressor gene and are influenced in a sex-biased manner to drive tumorigenesis in a mouse model. We think, based on what we’re seeing in human data, that there may be some relationships and we’re exploring that now as well. 

Q: What is your vision for the future in GI, and in your career?

The vision that I have is to create clinical tools that can expand our reach and our effectiveness and cancer prevention. I think that there are opportunities for leveraging microbiome research to accomplish this. And one outcome I could imagine is leveraging some of these insights to expand noninvasive screening at even earlier ages than we do now. I mean, we just dialed back the recommended age for colonoscopy for average risk individuals to 45. But I could envision a future in which noninvasive screening starts earlier, in which the first stool-based tests that we deploy to assess personalized risk are used in the pediatric clinic.

Lightning Round

Texting or talking?

Talking

Favorite city in the United States besides the one you live in?

St. Louis

Cat or dog person?

Both

If you weren’t a GI, what would you be?

Musician

Best place you went on vacation?

Borneo

Favorite sport?

Soccer

Favorite ice cream?

Cashew-based salted caramel

What song do you have to sing along with when you hear it?

Sweet Child of Mine

Favorite movie or TV show?

25th Hour or Shawshank Redemption

Optimist or Pessimist?

Optimist

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article 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.

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 metastatic hormone-sensitive prostate cancer and baseline bone pain at diagnosis have worse overall survival compared to those without bone pain, a post hoc study found.

METHODOLOGY:

• Prostate cancer often metastasizes to the bones, leading to pain and a reduced quality of life. While the relationship between bone pain and overall survival in metastatic, castration-resistant prostate cancer is well-documented, its impact in metastatic hormone-sensitive prostate cancer is less clear.
• Researchers conducted a post hoc secondary analysis using data from the SWOG-1216 phase 3 randomized clinical trial, which included 1279 men diagnosed with metastatic hormone-sensitive prostate cancer from 248 centers across the United States. Patients had received androgen deprivation therapy either with orteronel or bicalutamide.
• Among the 1197 patients (median age, 67.6 years) with data on bone pain included in the secondary analysis, 301 (23.5%) reported bone pain at baseline.
• The primary outcome was overall survival; secondary outcomes included progression-free survival and prostate-specific antigen response.

TAKEAWAY:

• The median overall survival for patients with baseline bone pain was 3.9 years compared with not reached (95% CI, 6.6 years to not reached) for those without bone pain at a median follow-up of 4 years (adjusted hazard ratio [aHR], 1.66; P < .001).
• Similarly, patients with bone pain had a shorter progression-free survival vs those without bone pain (median, 1.3 years vs 3.7 years; aHR, 1.46; P < .001).
• The complete prostate-specific antigen response rate at 7 months was also lower for patients with baseline bone pain (46.3% vs 66.3%; P < .001).

IN PRACTICE:

Patients with metastatic hormone-sensitive prostate cancer “with baseline bone pain had worse survival outcomes than those without baseline bone pain,” the authors wrote. “These results highlight the need to consider bone pain in prognostic modeling, treatment selection, patient monitoring, and follow-up and suggest prioritizing these patients for clinical trials and immediate systemic treatment initiation.”

SOURCE:

The study, led by Georges Gebrael, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, was published online in JAMA Network Open.

LIMITATIONS:

The post hoc design may introduce bias. Orteronel failed to receive regulatory approval, which may affect the generalizability of the findings. In addition, the study did not account for synchronous vs metachronous disease status, a known established prognostic factor.

DISCLOSURES:

The study was funded by the National Institutes of Health/National Cancer Institute and Millennium Pharmaceuticals (Takeda Oncology Company). Several authors declared 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:

Patients with metastatic hormone-sensitive prostate cancer and baseline bone pain at diagnosis have worse overall survival compared to those without bone pain, a post hoc study found.

METHODOLOGY:

• Prostate cancer often metastasizes to the bones, leading to pain and a reduced quality of life. While the relationship between bone pain and overall survival in metastatic, castration-resistant prostate cancer is well-documented, its impact in metastatic hormone-sensitive prostate cancer is less clear.
• Researchers conducted a post hoc secondary analysis using data from the SWOG-1216 phase 3 randomized clinical trial, which included 1279 men diagnosed with metastatic hormone-sensitive prostate cancer from 248 centers across the United States. Patients had received androgen deprivation therapy either with orteronel or bicalutamide.
• Among the 1197 patients (median age, 67.6 years) with data on bone pain included in the secondary analysis, 301 (23.5%) reported bone pain at baseline.
• The primary outcome was overall survival; secondary outcomes included progression-free survival and prostate-specific antigen response.

TAKEAWAY:

• The median overall survival for patients with baseline bone pain was 3.9 years compared with not reached (95% CI, 6.6 years to not reached) for those without bone pain at a median follow-up of 4 years (adjusted hazard ratio [aHR], 1.66; P < .001).
• Similarly, patients with bone pain had a shorter progression-free survival vs those without bone pain (median, 1.3 years vs 3.7 years; aHR, 1.46; P < .001).
• The complete prostate-specific antigen response rate at 7 months was also lower for patients with baseline bone pain (46.3% vs 66.3%; P < .001).

IN PRACTICE:

Patients with metastatic hormone-sensitive prostate cancer “with baseline bone pain had worse survival outcomes than those without baseline bone pain,” the authors wrote. “These results highlight the need to consider bone pain in prognostic modeling, treatment selection, patient monitoring, and follow-up and suggest prioritizing these patients for clinical trials and immediate systemic treatment initiation.”

SOURCE:

The study, led by Georges Gebrael, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, was published online in JAMA Network Open.

LIMITATIONS:

The post hoc design may introduce bias. Orteronel failed to receive regulatory approval, which may affect the generalizability of the findings. In addition, the study did not account for synchronous vs metachronous disease status, a known established prognostic factor.

DISCLOSURES:

The study was funded by the National Institutes of Health/National Cancer Institute and Millennium Pharmaceuticals (Takeda Oncology Company). Several authors declared 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:

Patients with metastatic hormone-sensitive prostate cancer and baseline bone pain at diagnosis have worse overall survival compared to those without bone pain, a post hoc study found.

METHODOLOGY:

• Prostate cancer often metastasizes to the bones, leading to pain and a reduced quality of life. While the relationship between bone pain and overall survival in metastatic, castration-resistant prostate cancer is well-documented, its impact in metastatic hormone-sensitive prostate cancer is less clear.
• Researchers conducted a post hoc secondary analysis using data from the SWOG-1216 phase 3 randomized clinical trial, which included 1279 men diagnosed with metastatic hormone-sensitive prostate cancer from 248 centers across the United States. Patients had received androgen deprivation therapy either with orteronel or bicalutamide.
• Among the 1197 patients (median age, 67.6 years) with data on bone pain included in the secondary analysis, 301 (23.5%) reported bone pain at baseline.
• The primary outcome was overall survival; secondary outcomes included progression-free survival and prostate-specific antigen response.

TAKEAWAY:

• The median overall survival for patients with baseline bone pain was 3.9 years compared with not reached (95% CI, 6.6 years to not reached) for those without bone pain at a median follow-up of 4 years (adjusted hazard ratio [aHR], 1.66; P < .001).
• Similarly, patients with bone pain had a shorter progression-free survival vs those without bone pain (median, 1.3 years vs 3.7 years; aHR, 1.46; P < .001).
• The complete prostate-specific antigen response rate at 7 months was also lower for patients with baseline bone pain (46.3% vs 66.3%; P < .001).

IN PRACTICE:

Patients with metastatic hormone-sensitive prostate cancer “with baseline bone pain had worse survival outcomes than those without baseline bone pain,” the authors wrote. “These results highlight the need to consider bone pain in prognostic modeling, treatment selection, patient monitoring, and follow-up and suggest prioritizing these patients for clinical trials and immediate systemic treatment initiation.”

SOURCE:

The study, led by Georges Gebrael, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, was published online in JAMA Network Open.

LIMITATIONS:

The post hoc design may introduce bias. Orteronel failed to receive regulatory approval, which may affect the generalizability of the findings. In addition, the study did not account for synchronous vs metachronous disease status, a known established prognostic factor.

DISCLOSURES:

The study was funded by the National Institutes of Health/National Cancer Institute and Millennium Pharmaceuticals (Takeda Oncology Company). Several authors declared 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.