Federal Practitioner

MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.

Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant therapy,” said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.

Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.

Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.

One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.

Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.

In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).

In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).

Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.

Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.

The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.

Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.

The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.

Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?

The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.

With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.

Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.

The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.

But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?

Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.

For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.

“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.

Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.

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

MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.

Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant therapy,” said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.

Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.

Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.

One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.

Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.

In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).

In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).

Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.

Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.

The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.

Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.

The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.

Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?

The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.

With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.

Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.

The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.

But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?

Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.

For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.

“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.

Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.

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

MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.

Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant therapy,” said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.

Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.

Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.

One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.

Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.

In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).

In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).

Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.

Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.

The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.

Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.

The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.

Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?

The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.

With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.

Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.

The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.

But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?

Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.

For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.

“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.

Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.

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

VANCOUVER – Two multitarget stool tests in development compare favorably for colorectal cancer (CRC) screening in average-risk people, suggest two new studies.

In a blinded, prospective, cross-sectional study, researchers assessed a multitarget stool RNA test (mt-sRNA; Colosense, Geneoscopy) vs. colonoscopy for detection of advanced adenomas and CRC in average-risk individuals aged 45 years and older.

In a prospective, cross-sectional study, investigators evaluated the clinical performance of a next-generation multitarget stool DNA (mt-sDNA; Cologuard, Exact Sciences) and fecal hemoglobin assay for CRC screening in adults aged 40 years and older.

Both studies were presented at the ACG: American College of Gastroenterology 2023 Annual Scientific Meeting.
 

RNA as a biomarker

For CRC-PREVENT, which evaluated the mt-sRNA test, David Lieberman, MD, professor of medicine and former chief of the division of gastroenterology and hepatology at the Oregon Health & Science University, Portland, and colleagues recruited a diverse group of 8,289 adults undergoing colonoscopy at one of more than 3,800 endoscopy centers nationwide. Recruitment included outreach through social media, which could be used to improve future screening rates, Dr. Lieberman said.

The full study findings of CRC-PREVENT were also published online in the Journal of the American Medical Association.

Participants provided stool samples before colonoscopy. Colosense includes a commercially available fecal immunochemical test (FIT) and tests for eight different strands of RNA. The mt-sRNA test results were compared with the colonoscopy results.

The mt-sRNA test had 100% sensitivity for early, stage I cancers, which were detected in 12 patients. Advanced adenomas were detected with an overall sensitivity of 45%. When the advanced adenomas were ≥ 2 cm, sensitivity increased to 51%.

Specificity was 87% among patients with negative findings for hyperplastic polyps or lesions.

The mt-sRNA test showed significant improvements in sensitivity for CRC (94% vs. 77%; P = .029) and advanced adenomas (45% vs 29%; P < .001), when compared with the FIT results alone.

“This is the first large study to include the 45- to 49-year-old population, for whom screening is now recommended,” Dr. Lieberman told this news organization.

Results show a sensitivity of 100% for detecting CRC and 44% for advanced adenomas in this younger age group. That performance is “excellent,” said Dr. Lieberman.

Results also were reliable across all ages.

“The consistent performance across all age groups for whom screening is recommended is a key finding and was totally unknown” before this study, Dr. Lieberman said.

RNA-based testing may have an advantage over DNA biomarker tests, which can be prone to age-related DNA methylation changes, he added.
 

Detection by DNA

Thomas Imperiale, MD, distinguished professor of medicine at Indiana University, Indianapolis, and colleagues conducted the BLUE-C trial to validate the next-generation mt-sDNA test for CRC screening.

The mt-sDNA assay tests for three novel methylated DNA markers and fecal hemoglobin.

Dr. Imperiale and colleagues studied 20,176 adults (mean age, 63 years) scheduled for screening colonoscopy at one of 186 U.S. sites. Participants provided a stool sample for the mt-sDNA test and comparator FIT prior to colonoscopy preparation. They compared results to colonoscopy and FIT findings.

Colonoscopy revealed 98 people with CRC, 2,144 with advanced precancerous lesions, and 17,934 with no advanced neoplasia.

Sensitivity of the mt-sDNA test for detecting CRC was 93.9% (95% confidence interval, 87.1-97.7), advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6), and advanced precancerous lesions with high-grade dysplasia was 74.6% (95% CI, 65.6-82.3).

Sensitivities of the mt-sDNA test for detecting CRC and advanced precancerous lesions were significantly higher than FIT (P < .0001).

In terms of specificity, the mt-sDNA test had a specificity of 90.6% (95% CI, 90.1-91.0) for the absence of advanced neoplasia. Specificity for non-neoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1).

The mt-sDNA test demonstrated high specificity and high CRC and advanced precancerous lesion sensitivity. The test outperformed FIT for these factors on sensitivity but not specificity, the authors noted.

Improved specificity was a goal of developing this next-generation assay. The BLUE-C trial demonstrated a 30% improvement in specificity that “will decrease the number of unnecessary colonoscopies performed for false-positive results,” said Dr. Imperiale.

“I was pleased to see the robust results support this new battery of markers,” Dr. Imperiale added. Improvements associated with this next-generation test could “help further reduce the incidence of and mortality from colorectal cancer.”
 

Tests to provide more noninvasive options

Both are “important studies” that look at a large, average-risk screening population in the United States, said Aasma Shaukat, MD, MPH, who was not affiliated with the research. “Both show high sensitivity for detecting CRC and decent specificity for advanced adenomas.”

While we will have to wait for the full publications, U.S. Food and Drug Administration approvals, and insurance coverage, gastroenterologists can expect to see these tests in clinical use in the near future, added Dr. Shaukat, professor of medicine and population health at NYU Langone Health, New York, and lead author of the ACG 2021 Colorectal Cancer Screening Guidelines.

These tests provide more noninvasive options for CRC screening and are more accurate, which hopefully will translate into increased screening and a reduced burden of CRC, she said.

“We are always looking for ways to increase colon cancer screening uptake,” said Brooks Cash, MD, professor and chief of the division of gastroenterology, hepatology, and nutrition at the University of Texas, Houston, who also was not affiliated with the research.

Certainly, the multitarget stool DNA is not a new concept with Cologuard, but it is a new assay, Dr. Cash said.

“It’s significantly different than their previous version, and they were able to show improved sensitivity as well as specificity, which has been one of the concerns,” he said.

The multitarget stool RNA test “shows very similar results,” Dr. Cash added. “Their predicate is that it’s slightly different and actually may return very good sensitivity for older patients, where you don’t have the same methylation issues with the DNA.”

“It will be interesting to see how they play out,” he added.

“The critical part to all of these tests is that if a patient has a positive test, they need to get a colonoscopy. That doesn’t always happen,” Dr. Cash said. “We have to make sure that there’s appropriate education for not only patients but also providers, many of whom will not be gastroenterologists.”

Geneoscopy funded the CRC-PREVENT trial. Exact Sciences funded the BLUE-C trial. Dr. Lieberman is an advisor or review panel member for Geneoscopy. Dr. Imperiale receives grant or research support from Exact Sciences. Dr. Shaukat reports no relevant financial relationships. Dr. Cash is on the advisory board for Exact Sciences.

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

VANCOUVER – Two multitarget stool tests in development compare favorably for colorectal cancer (CRC) screening in average-risk people, suggest two new studies.

In a blinded, prospective, cross-sectional study, researchers assessed a multitarget stool RNA test (mt-sRNA; Colosense, Geneoscopy) vs. colonoscopy for detection of advanced adenomas and CRC in average-risk individuals aged 45 years and older.

In a prospective, cross-sectional study, investigators evaluated the clinical performance of a next-generation multitarget stool DNA (mt-sDNA; Cologuard, Exact Sciences) and fecal hemoglobin assay for CRC screening in adults aged 40 years and older.

Both studies were presented at the ACG: American College of Gastroenterology 2023 Annual Scientific Meeting.
 

RNA as a biomarker

For CRC-PREVENT, which evaluated the mt-sRNA test, David Lieberman, MD, professor of medicine and former chief of the division of gastroenterology and hepatology at the Oregon Health & Science University, Portland, and colleagues recruited a diverse group of 8,289 adults undergoing colonoscopy at one of more than 3,800 endoscopy centers nationwide. Recruitment included outreach through social media, which could be used to improve future screening rates, Dr. Lieberman said.

The full study findings of CRC-PREVENT were also published online in the Journal of the American Medical Association.

Participants provided stool samples before colonoscopy. Colosense includes a commercially available fecal immunochemical test (FIT) and tests for eight different strands of RNA. The mt-sRNA test results were compared with the colonoscopy results.

The mt-sRNA test had 100% sensitivity for early, stage I cancers, which were detected in 12 patients. Advanced adenomas were detected with an overall sensitivity of 45%. When the advanced adenomas were ≥ 2 cm, sensitivity increased to 51%.

Specificity was 87% among patients with negative findings for hyperplastic polyps or lesions.

The mt-sRNA test showed significant improvements in sensitivity for CRC (94% vs. 77%; P = .029) and advanced adenomas (45% vs 29%; P < .001), when compared with the FIT results alone.

“This is the first large study to include the 45- to 49-year-old population, for whom screening is now recommended,” Dr. Lieberman told this news organization.

Results show a sensitivity of 100% for detecting CRC and 44% for advanced adenomas in this younger age group. That performance is “excellent,” said Dr. Lieberman.

Results also were reliable across all ages.

“The consistent performance across all age groups for whom screening is recommended is a key finding and was totally unknown” before this study, Dr. Lieberman said.

RNA-based testing may have an advantage over DNA biomarker tests, which can be prone to age-related DNA methylation changes, he added.
 

Detection by DNA

Thomas Imperiale, MD, distinguished professor of medicine at Indiana University, Indianapolis, and colleagues conducted the BLUE-C trial to validate the next-generation mt-sDNA test for CRC screening.

The mt-sDNA assay tests for three novel methylated DNA markers and fecal hemoglobin.

Dr. Imperiale and colleagues studied 20,176 adults (mean age, 63 years) scheduled for screening colonoscopy at one of 186 U.S. sites. Participants provided a stool sample for the mt-sDNA test and comparator FIT prior to colonoscopy preparation. They compared results to colonoscopy and FIT findings.

Colonoscopy revealed 98 people with CRC, 2,144 with advanced precancerous lesions, and 17,934 with no advanced neoplasia.

Sensitivity of the mt-sDNA test for detecting CRC was 93.9% (95% confidence interval, 87.1-97.7), advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6), and advanced precancerous lesions with high-grade dysplasia was 74.6% (95% CI, 65.6-82.3).

Sensitivities of the mt-sDNA test for detecting CRC and advanced precancerous lesions were significantly higher than FIT (P < .0001).

In terms of specificity, the mt-sDNA test had a specificity of 90.6% (95% CI, 90.1-91.0) for the absence of advanced neoplasia. Specificity for non-neoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1).

The mt-sDNA test demonstrated high specificity and high CRC and advanced precancerous lesion sensitivity. The test outperformed FIT for these factors on sensitivity but not specificity, the authors noted.

Improved specificity was a goal of developing this next-generation assay. The BLUE-C trial demonstrated a 30% improvement in specificity that “will decrease the number of unnecessary colonoscopies performed for false-positive results,” said Dr. Imperiale.

“I was pleased to see the robust results support this new battery of markers,” Dr. Imperiale added. Improvements associated with this next-generation test could “help further reduce the incidence of and mortality from colorectal cancer.”
 

Tests to provide more noninvasive options

Both are “important studies” that look at a large, average-risk screening population in the United States, said Aasma Shaukat, MD, MPH, who was not affiliated with the research. “Both show high sensitivity for detecting CRC and decent specificity for advanced adenomas.”

While we will have to wait for the full publications, U.S. Food and Drug Administration approvals, and insurance coverage, gastroenterologists can expect to see these tests in clinical use in the near future, added Dr. Shaukat, professor of medicine and population health at NYU Langone Health, New York, and lead author of the ACG 2021 Colorectal Cancer Screening Guidelines.

These tests provide more noninvasive options for CRC screening and are more accurate, which hopefully will translate into increased screening and a reduced burden of CRC, she said.

“We are always looking for ways to increase colon cancer screening uptake,” said Brooks Cash, MD, professor and chief of the division of gastroenterology, hepatology, and nutrition at the University of Texas, Houston, who also was not affiliated with the research.

Certainly, the multitarget stool DNA is not a new concept with Cologuard, but it is a new assay, Dr. Cash said.

“It’s significantly different than their previous version, and they were able to show improved sensitivity as well as specificity, which has been one of the concerns,” he said.

The multitarget stool RNA test “shows very similar results,” Dr. Cash added. “Their predicate is that it’s slightly different and actually may return very good sensitivity for older patients, where you don’t have the same methylation issues with the DNA.”

“It will be interesting to see how they play out,” he added.

“The critical part to all of these tests is that if a patient has a positive test, they need to get a colonoscopy. That doesn’t always happen,” Dr. Cash said. “We have to make sure that there’s appropriate education for not only patients but also providers, many of whom will not be gastroenterologists.”

Geneoscopy funded the CRC-PREVENT trial. Exact Sciences funded the BLUE-C trial. Dr. Lieberman is an advisor or review panel member for Geneoscopy. Dr. Imperiale receives grant or research support from Exact Sciences. Dr. Shaukat reports no relevant financial relationships. Dr. Cash is on the advisory board for Exact Sciences.

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

VANCOUVER – Two multitarget stool tests in development compare favorably for colorectal cancer (CRC) screening in average-risk people, suggest two new studies.

In a blinded, prospective, cross-sectional study, researchers assessed a multitarget stool RNA test (mt-sRNA; Colosense, Geneoscopy) vs. colonoscopy for detection of advanced adenomas and CRC in average-risk individuals aged 45 years and older.

In a prospective, cross-sectional study, investigators evaluated the clinical performance of a next-generation multitarget stool DNA (mt-sDNA; Cologuard, Exact Sciences) and fecal hemoglobin assay for CRC screening in adults aged 40 years and older.

Both studies were presented at the ACG: American College of Gastroenterology 2023 Annual Scientific Meeting.
 

RNA as a biomarker

For CRC-PREVENT, which evaluated the mt-sRNA test, David Lieberman, MD, professor of medicine and former chief of the division of gastroenterology and hepatology at the Oregon Health & Science University, Portland, and colleagues recruited a diverse group of 8,289 adults undergoing colonoscopy at one of more than 3,800 endoscopy centers nationwide. Recruitment included outreach through social media, which could be used to improve future screening rates, Dr. Lieberman said.

The full study findings of CRC-PREVENT were also published online in the Journal of the American Medical Association.

Participants provided stool samples before colonoscopy. Colosense includes a commercially available fecal immunochemical test (FIT) and tests for eight different strands of RNA. The mt-sRNA test results were compared with the colonoscopy results.

The mt-sRNA test had 100% sensitivity for early, stage I cancers, which were detected in 12 patients. Advanced adenomas were detected with an overall sensitivity of 45%. When the advanced adenomas were ≥ 2 cm, sensitivity increased to 51%.

Specificity was 87% among patients with negative findings for hyperplastic polyps or lesions.

The mt-sRNA test showed significant improvements in sensitivity for CRC (94% vs. 77%; P = .029) and advanced adenomas (45% vs 29%; P < .001), when compared with the FIT results alone.

“This is the first large study to include the 45- to 49-year-old population, for whom screening is now recommended,” Dr. Lieberman told this news organization.

Results show a sensitivity of 100% for detecting CRC and 44% for advanced adenomas in this younger age group. That performance is “excellent,” said Dr. Lieberman.

Results also were reliable across all ages.

“The consistent performance across all age groups for whom screening is recommended is a key finding and was totally unknown” before this study, Dr. Lieberman said.

RNA-based testing may have an advantage over DNA biomarker tests, which can be prone to age-related DNA methylation changes, he added.
 

Detection by DNA

Thomas Imperiale, MD, distinguished professor of medicine at Indiana University, Indianapolis, and colleagues conducted the BLUE-C trial to validate the next-generation mt-sDNA test for CRC screening.

The mt-sDNA assay tests for three novel methylated DNA markers and fecal hemoglobin.

Dr. Imperiale and colleagues studied 20,176 adults (mean age, 63 years) scheduled for screening colonoscopy at one of 186 U.S. sites. Participants provided a stool sample for the mt-sDNA test and comparator FIT prior to colonoscopy preparation. They compared results to colonoscopy and FIT findings.

Colonoscopy revealed 98 people with CRC, 2,144 with advanced precancerous lesions, and 17,934 with no advanced neoplasia.

Sensitivity of the mt-sDNA test for detecting CRC was 93.9% (95% confidence interval, 87.1-97.7), advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6), and advanced precancerous lesions with high-grade dysplasia was 74.6% (95% CI, 65.6-82.3).

Sensitivities of the mt-sDNA test for detecting CRC and advanced precancerous lesions were significantly higher than FIT (P < .0001).

In terms of specificity, the mt-sDNA test had a specificity of 90.6% (95% CI, 90.1-91.0) for the absence of advanced neoplasia. Specificity for non-neoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1).

The mt-sDNA test demonstrated high specificity and high CRC and advanced precancerous lesion sensitivity. The test outperformed FIT for these factors on sensitivity but not specificity, the authors noted.

Improved specificity was a goal of developing this next-generation assay. The BLUE-C trial demonstrated a 30% improvement in specificity that “will decrease the number of unnecessary colonoscopies performed for false-positive results,” said Dr. Imperiale.

“I was pleased to see the robust results support this new battery of markers,” Dr. Imperiale added. Improvements associated with this next-generation test could “help further reduce the incidence of and mortality from colorectal cancer.”
 

Tests to provide more noninvasive options

Both are “important studies” that look at a large, average-risk screening population in the United States, said Aasma Shaukat, MD, MPH, who was not affiliated with the research. “Both show high sensitivity for detecting CRC and decent specificity for advanced adenomas.”

While we will have to wait for the full publications, U.S. Food and Drug Administration approvals, and insurance coverage, gastroenterologists can expect to see these tests in clinical use in the near future, added Dr. Shaukat, professor of medicine and population health at NYU Langone Health, New York, and lead author of the ACG 2021 Colorectal Cancer Screening Guidelines.

These tests provide more noninvasive options for CRC screening and are more accurate, which hopefully will translate into increased screening and a reduced burden of CRC, she said.

“We are always looking for ways to increase colon cancer screening uptake,” said Brooks Cash, MD, professor and chief of the division of gastroenterology, hepatology, and nutrition at the University of Texas, Houston, who also was not affiliated with the research.

Certainly, the multitarget stool DNA is not a new concept with Cologuard, but it is a new assay, Dr. Cash said.

“It’s significantly different than their previous version, and they were able to show improved sensitivity as well as specificity, which has been one of the concerns,” he said.

The multitarget stool RNA test “shows very similar results,” Dr. Cash added. “Their predicate is that it’s slightly different and actually may return very good sensitivity for older patients, where you don’t have the same methylation issues with the DNA.”

“It will be interesting to see how they play out,” he added.

“The critical part to all of these tests is that if a patient has a positive test, they need to get a colonoscopy. That doesn’t always happen,” Dr. Cash said. “We have to make sure that there’s appropriate education for not only patients but also providers, many of whom will not be gastroenterologists.”

Geneoscopy funded the CRC-PREVENT trial. Exact Sciences funded the BLUE-C trial. Dr. Lieberman is an advisor or review panel member for Geneoscopy. Dr. Imperiale receives grant or research support from Exact Sciences. Dr. Shaukat reports no relevant financial relationships. Dr. Cash is on the advisory board for Exact Sciences.

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

NEW YORK – Peripheral T-cell lymphomas (PTCL) make up only about 10% of non-Hodgkin lymphomas, yet this disease presents a vexing problem. The majority of patients relapse, but efforts to develop new therapies are stymied by the rarity and genetic varieties of the condition.

University of Nebraska Medical Center

“Over the past 5 years, researchers have gotten a clearer picture of the different subtypes of peripheral T-cell lymphomas, and with this knowledge we are trying to identify potential targets of new treatments. Despite some progress, the need for these new treatments is still acute, due to the disease’s many subtypes and the difficulty of enrolling sufficient numbers of patients in clinical trials,” said Julie M. Vose, MD, MBA, of the University of Nebraska Medical Center, Omaha, speaking at the Lymphoma, Leukemia and Myeloma Congress 2023, in New York. Before her presentation at this year’s conference, Dr. Vose was awarded the SASS-ARENA Foundation’s John Ultmann Award for Major Contributions to Lymphoma Research.

Dr. Vose noted that only one subtype of PTCL, ALK+ ALCL, responds well to frontline treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). Patients with the ALK+ ALCL signature treated with CHOP have a 5-year overall survival (OS) rate of 70%-90%, but this group only makes up about 6% of PTCL cases in North America, she added.

One of the most promising breakthroughs in treatment has been the addition of the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) to chemotherapy with CHP (cyclophosphamide, doxorubicin, prednisone), Dr. Vose said. Results from the ECHELON-2 trial indicate that CD30+ PTCL patients have improved performance with R-CHP, compared with CHOP; 5-year progression free survival (PFS) rates were 51.4% with R+CHP versus 43.0% with CHOP, and 5-year overall survival rates were 70.1% versus 61.0%, respectively.

“ALCL is one of the most prevalent PTCL subtypes and accounts for about 24% of all PTCL; the current standard-of-care for induction treatment in these patients is BV-CHP,” said Jia Ruan, MD, PhD, of Weill Cornell Medicine in New York. Dr. Ruan explained the limitation of adding BV-CHP, saying “We don’t have as effective biological targeted therapies in other subtypes of T-cell lymphoma, such as PTCL NOS [not-other specified] or angioimmunoblastic T-cell lymphoma.”

There is evidence that autologous stem cell transplant (ACST) can increase PFS and OS in newly diagnosed patients with angioimmunoblastic T-cell lymphoma (AITL), but not in patients with other types of newly diagnosed PTCL. The estimated 2-year OS and PFS for patients with AITL who received ASCT + chemotherapy were 93.3% and 68.8 respectively versus 52.9% and 41.2 in the non-ASCT group. This news is promising, yet Dr. Vose presented statistics indicating that AITL PTCL has been estimated to account for less than 19% of PTCL cases.

Despite the improvements in PFS and OS in a few subtypes for frontline PTCL, 60% of patients with non-ALCL PTCL will relapse, and relapsed/ refractory (R/R) PTCL patients have a median PFS of 9.6 months. Several studies have shown some promise for improving outcomes in R/R PTCL patients, such as the phase-II PRIMO study of duvelisib (a dual PI3K-delta,gamma inhibitor), in which there was an overall response rate of 50% and a complete response rate of 32%. Despite these modest gains, the prognosis for most PTCL patients remains poor. Dr. Vose concluded her presentation by reiterating the need for new agents and for further research. She emphasized that studies will need to be collaborative and international to enroll sufficient patients.

Dr Ruan drew a similar conclusion, noting “We need to increase clinical, translational and basic research on a collaborative scale, so that we can advance bench-to-bedside discovery and bring new treatment to patients quickly.”

Dr. Vose disclosed research funding from Epizyme, GenMab, Kite, Novartis, and Lilly. Dr. Ruan disclosed clinical research trial support from BMS and Daiichi Sankyo.
 

NEW YORK – Peripheral T-cell lymphomas (PTCL) make up only about 10% of non-Hodgkin lymphomas, yet this disease presents a vexing problem. The majority of patients relapse, but efforts to develop new therapies are stymied by the rarity and genetic varieties of the condition.

University of Nebraska Medical Center

“Over the past 5 years, researchers have gotten a clearer picture of the different subtypes of peripheral T-cell lymphomas, and with this knowledge we are trying to identify potential targets of new treatments. Despite some progress, the need for these new treatments is still acute, due to the disease’s many subtypes and the difficulty of enrolling sufficient numbers of patients in clinical trials,” said Julie M. Vose, MD, MBA, of the University of Nebraska Medical Center, Omaha, speaking at the Lymphoma, Leukemia and Myeloma Congress 2023, in New York. Before her presentation at this year’s conference, Dr. Vose was awarded the SASS-ARENA Foundation’s John Ultmann Award for Major Contributions to Lymphoma Research.

Dr. Vose noted that only one subtype of PTCL, ALK+ ALCL, responds well to frontline treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). Patients with the ALK+ ALCL signature treated with CHOP have a 5-year overall survival (OS) rate of 70%-90%, but this group only makes up about 6% of PTCL cases in North America, she added.

One of the most promising breakthroughs in treatment has been the addition of the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) to chemotherapy with CHP (cyclophosphamide, doxorubicin, prednisone), Dr. Vose said. Results from the ECHELON-2 trial indicate that CD30+ PTCL patients have improved performance with R-CHP, compared with CHOP; 5-year progression free survival (PFS) rates were 51.4% with R+CHP versus 43.0% with CHOP, and 5-year overall survival rates were 70.1% versus 61.0%, respectively.

“ALCL is one of the most prevalent PTCL subtypes and accounts for about 24% of all PTCL; the current standard-of-care for induction treatment in these patients is BV-CHP,” said Jia Ruan, MD, PhD, of Weill Cornell Medicine in New York. Dr. Ruan explained the limitation of adding BV-CHP, saying “We don’t have as effective biological targeted therapies in other subtypes of T-cell lymphoma, such as PTCL NOS [not-other specified] or angioimmunoblastic T-cell lymphoma.”

There is evidence that autologous stem cell transplant (ACST) can increase PFS and OS in newly diagnosed patients with angioimmunoblastic T-cell lymphoma (AITL), but not in patients with other types of newly diagnosed PTCL. The estimated 2-year OS and PFS for patients with AITL who received ASCT + chemotherapy were 93.3% and 68.8 respectively versus 52.9% and 41.2 in the non-ASCT group. This news is promising, yet Dr. Vose presented statistics indicating that AITL PTCL has been estimated to account for less than 19% of PTCL cases.

Despite the improvements in PFS and OS in a few subtypes for frontline PTCL, 60% of patients with non-ALCL PTCL will relapse, and relapsed/ refractory (R/R) PTCL patients have a median PFS of 9.6 months. Several studies have shown some promise for improving outcomes in R/R PTCL patients, such as the phase-II PRIMO study of duvelisib (a dual PI3K-delta,gamma inhibitor), in which there was an overall response rate of 50% and a complete response rate of 32%. Despite these modest gains, the prognosis for most PTCL patients remains poor. Dr. Vose concluded her presentation by reiterating the need for new agents and for further research. She emphasized that studies will need to be collaborative and international to enroll sufficient patients.

Dr Ruan drew a similar conclusion, noting “We need to increase clinical, translational and basic research on a collaborative scale, so that we can advance bench-to-bedside discovery and bring new treatment to patients quickly.”

Dr. Vose disclosed research funding from Epizyme, GenMab, Kite, Novartis, and Lilly. Dr. Ruan disclosed clinical research trial support from BMS and Daiichi Sankyo.
 

NEW YORK – Peripheral T-cell lymphomas (PTCL) make up only about 10% of non-Hodgkin lymphomas, yet this disease presents a vexing problem. The majority of patients relapse, but efforts to develop new therapies are stymied by the rarity and genetic varieties of the condition.

University of Nebraska Medical Center

“Over the past 5 years, researchers have gotten a clearer picture of the different subtypes of peripheral T-cell lymphomas, and with this knowledge we are trying to identify potential targets of new treatments. Despite some progress, the need for these new treatments is still acute, due to the disease’s many subtypes and the difficulty of enrolling sufficient numbers of patients in clinical trials,” said Julie M. Vose, MD, MBA, of the University of Nebraska Medical Center, Omaha, speaking at the Lymphoma, Leukemia and Myeloma Congress 2023, in New York. Before her presentation at this year’s conference, Dr. Vose was awarded the SASS-ARENA Foundation’s John Ultmann Award for Major Contributions to Lymphoma Research.

Dr. Vose noted that only one subtype of PTCL, ALK+ ALCL, responds well to frontline treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). Patients with the ALK+ ALCL signature treated with CHOP have a 5-year overall survival (OS) rate of 70%-90%, but this group only makes up about 6% of PTCL cases in North America, she added.

One of the most promising breakthroughs in treatment has been the addition of the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) to chemotherapy with CHP (cyclophosphamide, doxorubicin, prednisone), Dr. Vose said. Results from the ECHELON-2 trial indicate that CD30+ PTCL patients have improved performance with R-CHP, compared with CHOP; 5-year progression free survival (PFS) rates were 51.4% with R+CHP versus 43.0% with CHOP, and 5-year overall survival rates were 70.1% versus 61.0%, respectively.

“ALCL is one of the most prevalent PTCL subtypes and accounts for about 24% of all PTCL; the current standard-of-care for induction treatment in these patients is BV-CHP,” said Jia Ruan, MD, PhD, of Weill Cornell Medicine in New York. Dr. Ruan explained the limitation of adding BV-CHP, saying “We don’t have as effective biological targeted therapies in other subtypes of T-cell lymphoma, such as PTCL NOS [not-other specified] or angioimmunoblastic T-cell lymphoma.”

There is evidence that autologous stem cell transplant (ACST) can increase PFS and OS in newly diagnosed patients with angioimmunoblastic T-cell lymphoma (AITL), but not in patients with other types of newly diagnosed PTCL. The estimated 2-year OS and PFS for patients with AITL who received ASCT + chemotherapy were 93.3% and 68.8 respectively versus 52.9% and 41.2 in the non-ASCT group. This news is promising, yet Dr. Vose presented statistics indicating that AITL PTCL has been estimated to account for less than 19% of PTCL cases.

Despite the improvements in PFS and OS in a few subtypes for frontline PTCL, 60% of patients with non-ALCL PTCL will relapse, and relapsed/ refractory (R/R) PTCL patients have a median PFS of 9.6 months. Several studies have shown some promise for improving outcomes in R/R PTCL patients, such as the phase-II PRIMO study of duvelisib (a dual PI3K-delta,gamma inhibitor), in which there was an overall response rate of 50% and a complete response rate of 32%. Despite these modest gains, the prognosis for most PTCL patients remains poor. Dr. Vose concluded her presentation by reiterating the need for new agents and for further research. She emphasized that studies will need to be collaborative and international to enroll sufficient patients.

Dr Ruan drew a similar conclusion, noting “We need to increase clinical, translational and basic research on a collaborative scale, so that we can advance bench-to-bedside discovery and bring new treatment to patients quickly.”

Dr. Vose disclosed research funding from Epizyme, GenMab, Kite, Novartis, and Lilly. Dr. Ruan disclosed clinical research trial support from BMS and Daiichi Sankyo.
 

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

MADRID – New data from three trials evaluating the bispecific antibody amivantamab (Rybrevant) in EGFR-mutated advanced non–small cell lung cancer (NSCLC) have revealed a clear benefit, experts said at the annual meeting of the European Society for Medical Oncology (ESMO).

The results of the three trials – PAPILLON, MARIPOSA, and MARIPOSA-2 – are “really exciting” for patients harboring EGFR mutations, said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland, and the ESMO 2023 scientific chair.

Presenting findings from PAPILLON, Nicolas Girard, MD, PhD, highlighted outcomes among patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2%-3% of NSCLC cases, have “historically poor” outcomes, with a 5-year overall survival rate of just 8%.

Tumors harboring exon 20 insertions are largely insensitive to targeted and immune checkpoint therapies, explained Dr. Girard, from Curie-Montsouris Thorax Institute, Institut Curie, Paris. That leaves platinum-based chemotherapy as the standard of care, which has “limited efficacy,” he noted.

The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.

In the trial, 308 treatment-naive patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian – a similar patient profile as MARIPOSA and MARIPOSA-2.

The results, simultaneously published in The New England Journal of Medicine, showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs. 5.7 months with chemotherapy alone (hazard ratio, 0.395; P < .0001). This benefit consistently occurred across predefined subgroups.

Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs. 17.2 months with chemotherapy alone (HR, 0.493; P = .001).

A higher proportion of patients receiving the combination had an objective response – 73% vs. 47% – and these patients had a longer duration of response as well – 9.7 months vs. 4.4 months.

The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106).

The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.

Dr. Girard concluded that, with a safety profile “consistent” with that seen for the individual agents, amivantamab plus chemotherapy “represents a new standard of care” for first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC.

Benjamin Besse, MD, PhD, who was not involved in the research, agreed that this combination is “definitely a new standard of care.”

The effect of giving amivantamab alongside chemotherapy “seems to be really additive,” said Dr. Besse, director of clinical research at the Gustave Roussy Institute and professor of medical oncology at Paris-Saclay University, both in Paris. But he noted that amivantamab is a “challenging drug in terms of toxicity.”
 

The MARIPOSA trials

The two MARIPOSA trials also demonstrated that amivantamab, in combination with other agents, improved PFS among patients with EGFR-mutated advanced NSCLC.

Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, South Korea, presented results from MARIPOSA, which focused on patients with any kind of EGFR mutation.

Although the EGFR tyrosine kinase inhibitor (TKI) osimertinib is the current standard of care in this first-line setting, “resistance and disease progression are nearly inevitable,” and secondary EGFR and MET mutations may account for up to 50% of tumor resistance, Dr. Cho noted.

Early clinical data suggest that combining amivantamab with the highly selective third-generation EGFR TKI lazertinib leads to clinical activity and durable responses.

For the phase 3 MARIPOSA trial, 1,074 patients with treatment-naive locally advanced or metastatic EGFR-mutant NSCLC were randomly assigned to amivantamab plus lazertinib (n = 429), osimertinib alone (n = 429), or lazertinib alone (n = 216).

After a median follow-up of 22 months, the median PFS among patients on the combination was 23.7 months vs. 16.6 months for those on osimertinib alone (HR, 0.70; P < .001) and 18.5 months for those on lazertinib alone.

The PFS benefit observed with amivantamab plus lazertinib occurred across subgroups, including among patients with brain metastases. The combination reduced the risk for extracranial progression or death by 32% and improved median PFS by 9 months, compared with osimertinib alone (HR, 0.68; P < .001).

The risk for a second progression was also lower with the combination (HR, 0.75).

Interim overall survival data suggested a benefit with the combination therapy, compared with osimertinib alone (HR, 0.80; P = .11).

Grade 3 or higher adverse events were more common among patients treated with the combination vs. osimertinib alone – 75% vs. 43%. Higher rates of treatment-related discontinuation of any agent were observed in the combination group – 35% vs. 14% – though rates of adverse events leading to death were similar between the groups – 8% and 7%, respectively.

As in PAPILLON, rates of ILD/pneumonitis were “low,” said Dr. Cho, at approximately 3% in both treatment arms. However, he noted, rates of venous thromboembolism were higher with the combination, with grade ≥ 3 events occurring in 11% vs. 3.7% of patients on osimertinib.

Based on the findings, amivantamab plus lazertinib “represents a new standard of care in first-line EGFR-mutant advanced NSCLC,” Dr. Cho said. “It has been a long way and we finally made it.”

Next up is MARIPOSA-2, which evaluated patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on or after osimertinib.

In this trial, 657 patients were randomly assigned to amivantamab plus lazertinib and chemotherapy (n = 263), amivantamab plus chemotherapy (n = 263), or chemotherapy alone (n = 131).

Given the increased risk for hematologic toxicities, the study protocol was adjusted in the triple therapy arm so that patients received lazertinib after completing carboplatin.

The findings, presented by study investigator Antonio Passaro, MD, PhD, were simultaneously published in Annals of Oncology.

After a median follow-up of 8.7 months, the triple therapy reduced the risk for progression or death by 56% (HR,0.44) and amivantamab plus chemotherapy reduced the risk for progression or death by 52% (HR, 0.48). Overall, the median PFS was 8.3 months in the triple combination arm, 6.3 months in the amivantamab plus chemotherapy arm, and 4.2 months in the chemotherapy arm.

This PFS benefit was observed across prespecified subgroups with both combination therapies. The combinations also reduced the risk for intracranial progression (HR, 0.58 in the triple therapy arm; HR, 0.55 in the amivantamab plus chemotherapy arm).

The current interim analysis did not show an overall survival benefit with either combination therapy vs. chemotherapy alone, although the survival curve hinted at a benefit in the amivantamab plus chemotherapy arm.

The median duration of response was 9.4 months for triple therapy, 6.9 months for the double combination, and 5.6 months for monotherapy.

Rates of grade ≥ 3 adverse events were notably higher in the combination groups – 92% of patients on triple therapy, 72% on double, and 48% on chemotherapy alone. But the treatment duration was longer in the combination groups and adverse events leading to death were low, as was discontinuation.

Amivantamab plus chemotherapy or plus lazertinib and chemotherapy are the “first regimens to demonstrate improved PFS vs. chemotherapy in EGFR-mutated NSCLC after disease progression on osimertinib,” concluded Dr. Passaro, from the European Institute of Oncology IRCCS, Milan, who presented the findings.

Dr. Passaro added that, given the consistent efficacy and more favorable safety profile, “we can say that amivantamab plus chemotherapy is the new standard of care for patients that are progressing after osimertinib,” although more follow-up is required to understand its “real impact” in the clinic.

Zofia Piotrowska, MD, who was not involved in either MARIPOSA trial, said both “are really important” in the EGFR-mutant NSCLC space.

The studies “addressed two different questions,” but both were “positive, and I think clinically significantly,” said Dr. Piotrowska, a lung cancer specialist at Massachusetts General Hospital Cancer Center, Boston.

However, Dr. Piotrowska noted that a core question for the community will be “how we find that balance between the clinical benefits [and] the toxicities.”

“There’s not going to be one easy answer” and treatment selection will have to be made on a “patient-by-patient basis,” she said.

PAPILLON, MARIPOSA, and MARIPOSA-2 were funded by Janssen Pharmaceuticals. Dr. Girard declared relationships with AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, and others. Dr. Cho declared relationships with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Onegene Biotechnology, Pfizer, Eli Lilly, and others. Dr. Passaro declared relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer, Boehringer-Ingelheim, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, and eCancer. Dr. Besse declared institutional relationships with AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi-Sankyo, Eli Lilly, EISAI, Genzyme Corporation, GSK, and others. Dr. Piotrowska declared relationships with numerous companies including AstraZeneca, Novartis, and Takeda.

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

MADRID – New data from three trials evaluating the bispecific antibody amivantamab (Rybrevant) in EGFR-mutated advanced non–small cell lung cancer (NSCLC) have revealed a clear benefit, experts said at the annual meeting of the European Society for Medical Oncology (ESMO).

The results of the three trials – PAPILLON, MARIPOSA, and MARIPOSA-2 – are “really exciting” for patients harboring EGFR mutations, said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland, and the ESMO 2023 scientific chair.

Presenting findings from PAPILLON, Nicolas Girard, MD, PhD, highlighted outcomes among patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2%-3% of NSCLC cases, have “historically poor” outcomes, with a 5-year overall survival rate of just 8%.

Tumors harboring exon 20 insertions are largely insensitive to targeted and immune checkpoint therapies, explained Dr. Girard, from Curie-Montsouris Thorax Institute, Institut Curie, Paris. That leaves platinum-based chemotherapy as the standard of care, which has “limited efficacy,” he noted.

The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.

In the trial, 308 treatment-naive patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian – a similar patient profile as MARIPOSA and MARIPOSA-2.

The results, simultaneously published in The New England Journal of Medicine, showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs. 5.7 months with chemotherapy alone (hazard ratio, 0.395; P < .0001). This benefit consistently occurred across predefined subgroups.

Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs. 17.2 months with chemotherapy alone (HR, 0.493; P = .001).

A higher proportion of patients receiving the combination had an objective response – 73% vs. 47% – and these patients had a longer duration of response as well – 9.7 months vs. 4.4 months.

The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106).

The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.

Dr. Girard concluded that, with a safety profile “consistent” with that seen for the individual agents, amivantamab plus chemotherapy “represents a new standard of care” for first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC.

Benjamin Besse, MD, PhD, who was not involved in the research, agreed that this combination is “definitely a new standard of care.”

The effect of giving amivantamab alongside chemotherapy “seems to be really additive,” said Dr. Besse, director of clinical research at the Gustave Roussy Institute and professor of medical oncology at Paris-Saclay University, both in Paris. But he noted that amivantamab is a “challenging drug in terms of toxicity.”
 

The MARIPOSA trials

The two MARIPOSA trials also demonstrated that amivantamab, in combination with other agents, improved PFS among patients with EGFR-mutated advanced NSCLC.

Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, South Korea, presented results from MARIPOSA, which focused on patients with any kind of EGFR mutation.

Although the EGFR tyrosine kinase inhibitor (TKI) osimertinib is the current standard of care in this first-line setting, “resistance and disease progression are nearly inevitable,” and secondary EGFR and MET mutations may account for up to 50% of tumor resistance, Dr. Cho noted.

Early clinical data suggest that combining amivantamab with the highly selective third-generation EGFR TKI lazertinib leads to clinical activity and durable responses.

For the phase 3 MARIPOSA trial, 1,074 patients with treatment-naive locally advanced or metastatic EGFR-mutant NSCLC were randomly assigned to amivantamab plus lazertinib (n = 429), osimertinib alone (n = 429), or lazertinib alone (n = 216).

After a median follow-up of 22 months, the median PFS among patients on the combination was 23.7 months vs. 16.6 months for those on osimertinib alone (HR, 0.70; P < .001) and 18.5 months for those on lazertinib alone.

The PFS benefit observed with amivantamab plus lazertinib occurred across subgroups, including among patients with brain metastases. The combination reduced the risk for extracranial progression or death by 32% and improved median PFS by 9 months, compared with osimertinib alone (HR, 0.68; P < .001).

The risk for a second progression was also lower with the combination (HR, 0.75).

Interim overall survival data suggested a benefit with the combination therapy, compared with osimertinib alone (HR, 0.80; P = .11).

Grade 3 or higher adverse events were more common among patients treated with the combination vs. osimertinib alone – 75% vs. 43%. Higher rates of treatment-related discontinuation of any agent were observed in the combination group – 35% vs. 14% – though rates of adverse events leading to death were similar between the groups – 8% and 7%, respectively.

As in PAPILLON, rates of ILD/pneumonitis were “low,” said Dr. Cho, at approximately 3% in both treatment arms. However, he noted, rates of venous thromboembolism were higher with the combination, with grade ≥ 3 events occurring in 11% vs. 3.7% of patients on osimertinib.

Based on the findings, amivantamab plus lazertinib “represents a new standard of care in first-line EGFR-mutant advanced NSCLC,” Dr. Cho said. “It has been a long way and we finally made it.”

Next up is MARIPOSA-2, which evaluated patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on or after osimertinib.

In this trial, 657 patients were randomly assigned to amivantamab plus lazertinib and chemotherapy (n = 263), amivantamab plus chemotherapy (n = 263), or chemotherapy alone (n = 131).

Given the increased risk for hematologic toxicities, the study protocol was adjusted in the triple therapy arm so that patients received lazertinib after completing carboplatin.

The findings, presented by study investigator Antonio Passaro, MD, PhD, were simultaneously published in Annals of Oncology.

After a median follow-up of 8.7 months, the triple therapy reduced the risk for progression or death by 56% (HR,0.44) and amivantamab plus chemotherapy reduced the risk for progression or death by 52% (HR, 0.48). Overall, the median PFS was 8.3 months in the triple combination arm, 6.3 months in the amivantamab plus chemotherapy arm, and 4.2 months in the chemotherapy arm.

This PFS benefit was observed across prespecified subgroups with both combination therapies. The combinations also reduced the risk for intracranial progression (HR, 0.58 in the triple therapy arm; HR, 0.55 in the amivantamab plus chemotherapy arm).

The current interim analysis did not show an overall survival benefit with either combination therapy vs. chemotherapy alone, although the survival curve hinted at a benefit in the amivantamab plus chemotherapy arm.

The median duration of response was 9.4 months for triple therapy, 6.9 months for the double combination, and 5.6 months for monotherapy.

Rates of grade ≥ 3 adverse events were notably higher in the combination groups – 92% of patients on triple therapy, 72% on double, and 48% on chemotherapy alone. But the treatment duration was longer in the combination groups and adverse events leading to death were low, as was discontinuation.

Amivantamab plus chemotherapy or plus lazertinib and chemotherapy are the “first regimens to demonstrate improved PFS vs. chemotherapy in EGFR-mutated NSCLC after disease progression on osimertinib,” concluded Dr. Passaro, from the European Institute of Oncology IRCCS, Milan, who presented the findings.

Dr. Passaro added that, given the consistent efficacy and more favorable safety profile, “we can say that amivantamab plus chemotherapy is the new standard of care for patients that are progressing after osimertinib,” although more follow-up is required to understand its “real impact” in the clinic.

Zofia Piotrowska, MD, who was not involved in either MARIPOSA trial, said both “are really important” in the EGFR-mutant NSCLC space.

The studies “addressed two different questions,” but both were “positive, and I think clinically significantly,” said Dr. Piotrowska, a lung cancer specialist at Massachusetts General Hospital Cancer Center, Boston.

However, Dr. Piotrowska noted that a core question for the community will be “how we find that balance between the clinical benefits [and] the toxicities.”

“There’s not going to be one easy answer” and treatment selection will have to be made on a “patient-by-patient basis,” she said.

PAPILLON, MARIPOSA, and MARIPOSA-2 were funded by Janssen Pharmaceuticals. Dr. Girard declared relationships with AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, and others. Dr. Cho declared relationships with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Onegene Biotechnology, Pfizer, Eli Lilly, and others. Dr. Passaro declared relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer, Boehringer-Ingelheim, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, and eCancer. Dr. Besse declared institutional relationships with AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi-Sankyo, Eli Lilly, EISAI, Genzyme Corporation, GSK, and others. Dr. Piotrowska declared relationships with numerous companies including AstraZeneca, Novartis, and Takeda.

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

MADRID – New data from three trials evaluating the bispecific antibody amivantamab (Rybrevant) in EGFR-mutated advanced non–small cell lung cancer (NSCLC) have revealed a clear benefit, experts said at the annual meeting of the European Society for Medical Oncology (ESMO).

The results of the three trials – PAPILLON, MARIPOSA, and MARIPOSA-2 – are “really exciting” for patients harboring EGFR mutations, said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland, and the ESMO 2023 scientific chair.

Presenting findings from PAPILLON, Nicolas Girard, MD, PhD, highlighted outcomes among patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2%-3% of NSCLC cases, have “historically poor” outcomes, with a 5-year overall survival rate of just 8%.

Tumors harboring exon 20 insertions are largely insensitive to targeted and immune checkpoint therapies, explained Dr. Girard, from Curie-Montsouris Thorax Institute, Institut Curie, Paris. That leaves platinum-based chemotherapy as the standard of care, which has “limited efficacy,” he noted.

The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.

In the trial, 308 treatment-naive patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian – a similar patient profile as MARIPOSA and MARIPOSA-2.

The results, simultaneously published in The New England Journal of Medicine, showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs. 5.7 months with chemotherapy alone (hazard ratio, 0.395; P < .0001). This benefit consistently occurred across predefined subgroups.

Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs. 17.2 months with chemotherapy alone (HR, 0.493; P = .001).

A higher proportion of patients receiving the combination had an objective response – 73% vs. 47% – and these patients had a longer duration of response as well – 9.7 months vs. 4.4 months.

The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106).

The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.

Dr. Girard concluded that, with a safety profile “consistent” with that seen for the individual agents, amivantamab plus chemotherapy “represents a new standard of care” for first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC.

Benjamin Besse, MD, PhD, who was not involved in the research, agreed that this combination is “definitely a new standard of care.”

The effect of giving amivantamab alongside chemotherapy “seems to be really additive,” said Dr. Besse, director of clinical research at the Gustave Roussy Institute and professor of medical oncology at Paris-Saclay University, both in Paris. But he noted that amivantamab is a “challenging drug in terms of toxicity.”
 

The MARIPOSA trials

The two MARIPOSA trials also demonstrated that amivantamab, in combination with other agents, improved PFS among patients with EGFR-mutated advanced NSCLC.

Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, South Korea, presented results from MARIPOSA, which focused on patients with any kind of EGFR mutation.

Although the EGFR tyrosine kinase inhibitor (TKI) osimertinib is the current standard of care in this first-line setting, “resistance and disease progression are nearly inevitable,” and secondary EGFR and MET mutations may account for up to 50% of tumor resistance, Dr. Cho noted.

Early clinical data suggest that combining amivantamab with the highly selective third-generation EGFR TKI lazertinib leads to clinical activity and durable responses.

For the phase 3 MARIPOSA trial, 1,074 patients with treatment-naive locally advanced or metastatic EGFR-mutant NSCLC were randomly assigned to amivantamab plus lazertinib (n = 429), osimertinib alone (n = 429), or lazertinib alone (n = 216).

After a median follow-up of 22 months, the median PFS among patients on the combination was 23.7 months vs. 16.6 months for those on osimertinib alone (HR, 0.70; P < .001) and 18.5 months for those on lazertinib alone.

The PFS benefit observed with amivantamab plus lazertinib occurred across subgroups, including among patients with brain metastases. The combination reduced the risk for extracranial progression or death by 32% and improved median PFS by 9 months, compared with osimertinib alone (HR, 0.68; P < .001).

The risk for a second progression was also lower with the combination (HR, 0.75).

Interim overall survival data suggested a benefit with the combination therapy, compared with osimertinib alone (HR, 0.80; P = .11).

Grade 3 or higher adverse events were more common among patients treated with the combination vs. osimertinib alone – 75% vs. 43%. Higher rates of treatment-related discontinuation of any agent were observed in the combination group – 35% vs. 14% – though rates of adverse events leading to death were similar between the groups – 8% and 7%, respectively.

As in PAPILLON, rates of ILD/pneumonitis were “low,” said Dr. Cho, at approximately 3% in both treatment arms. However, he noted, rates of venous thromboembolism were higher with the combination, with grade ≥ 3 events occurring in 11% vs. 3.7% of patients on osimertinib.

Based on the findings, amivantamab plus lazertinib “represents a new standard of care in first-line EGFR-mutant advanced NSCLC,” Dr. Cho said. “It has been a long way and we finally made it.”

Next up is MARIPOSA-2, which evaluated patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on or after osimertinib.

In this trial, 657 patients were randomly assigned to amivantamab plus lazertinib and chemotherapy (n = 263), amivantamab plus chemotherapy (n = 263), or chemotherapy alone (n = 131).

Given the increased risk for hematologic toxicities, the study protocol was adjusted in the triple therapy arm so that patients received lazertinib after completing carboplatin.

The findings, presented by study investigator Antonio Passaro, MD, PhD, were simultaneously published in Annals of Oncology.

After a median follow-up of 8.7 months, the triple therapy reduced the risk for progression or death by 56% (HR,0.44) and amivantamab plus chemotherapy reduced the risk for progression or death by 52% (HR, 0.48). Overall, the median PFS was 8.3 months in the triple combination arm, 6.3 months in the amivantamab plus chemotherapy arm, and 4.2 months in the chemotherapy arm.

This PFS benefit was observed across prespecified subgroups with both combination therapies. The combinations also reduced the risk for intracranial progression (HR, 0.58 in the triple therapy arm; HR, 0.55 in the amivantamab plus chemotherapy arm).

The current interim analysis did not show an overall survival benefit with either combination therapy vs. chemotherapy alone, although the survival curve hinted at a benefit in the amivantamab plus chemotherapy arm.

The median duration of response was 9.4 months for triple therapy, 6.9 months for the double combination, and 5.6 months for monotherapy.

Rates of grade ≥ 3 adverse events were notably higher in the combination groups – 92% of patients on triple therapy, 72% on double, and 48% on chemotherapy alone. But the treatment duration was longer in the combination groups and adverse events leading to death were low, as was discontinuation.

Amivantamab plus chemotherapy or plus lazertinib and chemotherapy are the “first regimens to demonstrate improved PFS vs. chemotherapy in EGFR-mutated NSCLC after disease progression on osimertinib,” concluded Dr. Passaro, from the European Institute of Oncology IRCCS, Milan, who presented the findings.

Dr. Passaro added that, given the consistent efficacy and more favorable safety profile, “we can say that amivantamab plus chemotherapy is the new standard of care for patients that are progressing after osimertinib,” although more follow-up is required to understand its “real impact” in the clinic.

Zofia Piotrowska, MD, who was not involved in either MARIPOSA trial, said both “are really important” in the EGFR-mutant NSCLC space.

The studies “addressed two different questions,” but both were “positive, and I think clinically significantly,” said Dr. Piotrowska, a lung cancer specialist at Massachusetts General Hospital Cancer Center, Boston.

However, Dr. Piotrowska noted that a core question for the community will be “how we find that balance between the clinical benefits [and] the toxicities.”

“There’s not going to be one easy answer” and treatment selection will have to be made on a “patient-by-patient basis,” she said.

PAPILLON, MARIPOSA, and MARIPOSA-2 were funded by Janssen Pharmaceuticals. Dr. Girard declared relationships with AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, and others. Dr. Cho declared relationships with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Onegene Biotechnology, Pfizer, Eli Lilly, and others. Dr. Passaro declared relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer, Boehringer-Ingelheim, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, and eCancer. Dr. Besse declared institutional relationships with AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi-Sankyo, Eli Lilly, EISAI, Genzyme Corporation, GSK, and others. Dr. Piotrowska declared relationships with numerous companies including AstraZeneca, Novartis, and Takeda.

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

Six weeks of induction chemotherapy before definitive chemoradiation for locally advanced cervical cancer substantially improves progression-free and overall survival and should be considered the new standard of care, according to Mary McCormack, MBBS, PhD, a gynecologic and breast oncologist at the University College Hospital, London.

Dr. McCormack was the lead investigator on a phase 3 trial called INTERLACE that tested the approach against stand-alone chemoradiation – the current standard of care – in 500 women, majority in the United Kingdom and Mexico.

She made her comments after presenting the results at the annual meeting of the European Society for Medical Oncology.

The 250 women randomized to induction chemotherapy before chemoradiation (CRT) had a 35% improvement in progression-free survival (PFS), with a 5-year PFS of 73% versus 64% among 250 randomized to CRT alone. Likewise, overall survival (OS) improved 39% in the induction group, with a 5-year OS of 80% versus 72% among women who went straight to CRT.

Induction chemotherapy consisted of 6 weekly doses of carboplatin AUC2 and paclitaxel 80 mg/m² followed by CRT within 7 days. CRT consisted of 5 weekly doses of cisplatin 40 mg/m² plus external beam radiotherapy and brachytherapy. Compliance in both arms was high.

“Induction chemotherapy with weekly paclitaxel and carboplatin delivered immediately before chemoradiotherapy should be considered the new standard in locally advanced cervical cancer, and [it] is feasible across diverse healthcare settings,” Dr. McCormack said.

Study discussant Krishnansu Tewari, MD, a gynecologic oncologist at the University of California, Irvine, was impressed by the results.

“This is the first phase 3 randomized trial in locally advanced cervical cancer that has shown [an overall] survival benefit in over 2 decades. Physicians taking care of these patients could consider induction chemotherapy ... tomorrow morning,” he said.

Dr. Tewari brought up how to incorporate the findings with another trial presented earlier at the meeting, KEYNOTE-A18.

KEYNOTE-A18 added pembrolizumab to CRT, which resulted in substantially better PFS and a strong trend towards better OS that could reach statistical significance with additional follow-up.

Both trials are “practice changing” for locally advanced cervical cancer. “I think we are ready for a paradigm shift,” Dr. Tewari said.

He noted a limit in the INTERLACE presentation was that outcomes were not broken down by tumor stage.

Over three-quarters of the women had stage 2 disease; 9% had stage 1 disease, and only 14% had stage 3B or 4A tumors. Almost 60% of the women were node negative.

It’s unclear at this point if women who have node-negative stage 1B3 or stage 2A-B disease “really need induction chemotherapy. I would think that those patients are probably curable by standard chemoradiation plus brachytherapy, and that the real [benefit would be] for stage 3B and 4A patients,” he said.

The median age in the study was 46 years, and 82% of the women had squamous cell tumors.

Grade 3/4 adverse events were higher in the induction arm, 59% versus 48%, driven mostly by a higher incidence of neutropenia and other hematologic adverse events with induction.

One woman died of adverse events in the induction arm and two died in the CRT-alone arm.

Local and pelvic relapse rates were equal in both groups at 16%, but total distant relapses were lower with induction chemotherapy, 12% versus 20%, over a median follow-up of 64 months.

The work was funded by Cancer Research UK. Dr. McCormack is a consultant for AstraZeneca, Eisai, and GSK, and disclosed honoraria/meeting expenses from Daiicho Sankyo, Roche, and Medscape, the publisher of this article. Among other industry ties, Dr. Tewari is an advisor/consultant, researcher, and speaker for Merck, SeaGen, and AstraZeneca.

Six weeks of induction chemotherapy before definitive chemoradiation for locally advanced cervical cancer substantially improves progression-free and overall survival and should be considered the new standard of care, according to Mary McCormack, MBBS, PhD, a gynecologic and breast oncologist at the University College Hospital, London.

Dr. McCormack was the lead investigator on a phase 3 trial called INTERLACE that tested the approach against stand-alone chemoradiation – the current standard of care – in 500 women, majority in the United Kingdom and Mexico.

She made her comments after presenting the results at the annual meeting of the European Society for Medical Oncology.

The 250 women randomized to induction chemotherapy before chemoradiation (CRT) had a 35% improvement in progression-free survival (PFS), with a 5-year PFS of 73% versus 64% among 250 randomized to CRT alone. Likewise, overall survival (OS) improved 39% in the induction group, with a 5-year OS of 80% versus 72% among women who went straight to CRT.

Induction chemotherapy consisted of 6 weekly doses of carboplatin AUC2 and paclitaxel 80 mg/m² followed by CRT within 7 days. CRT consisted of 5 weekly doses of cisplatin 40 mg/m² plus external beam radiotherapy and brachytherapy. Compliance in both arms was high.

“Induction chemotherapy with weekly paclitaxel and carboplatin delivered immediately before chemoradiotherapy should be considered the new standard in locally advanced cervical cancer, and [it] is feasible across diverse healthcare settings,” Dr. McCormack said.

Study discussant Krishnansu Tewari, MD, a gynecologic oncologist at the University of California, Irvine, was impressed by the results.

“This is the first phase 3 randomized trial in locally advanced cervical cancer that has shown [an overall] survival benefit in over 2 decades. Physicians taking care of these patients could consider induction chemotherapy ... tomorrow morning,” he said.

Dr. Tewari brought up how to incorporate the findings with another trial presented earlier at the meeting, KEYNOTE-A18.

KEYNOTE-A18 added pembrolizumab to CRT, which resulted in substantially better PFS and a strong trend towards better OS that could reach statistical significance with additional follow-up.

Both trials are “practice changing” for locally advanced cervical cancer. “I think we are ready for a paradigm shift,” Dr. Tewari said.

He noted a limit in the INTERLACE presentation was that outcomes were not broken down by tumor stage.

Over three-quarters of the women had stage 2 disease; 9% had stage 1 disease, and only 14% had stage 3B or 4A tumors. Almost 60% of the women were node negative.

It’s unclear at this point if women who have node-negative stage 1B3 or stage 2A-B disease “really need induction chemotherapy. I would think that those patients are probably curable by standard chemoradiation plus brachytherapy, and that the real [benefit would be] for stage 3B and 4A patients,” he said.

The median age in the study was 46 years, and 82% of the women had squamous cell tumors.

Grade 3/4 adverse events were higher in the induction arm, 59% versus 48%, driven mostly by a higher incidence of neutropenia and other hematologic adverse events with induction.

One woman died of adverse events in the induction arm and two died in the CRT-alone arm.

Local and pelvic relapse rates were equal in both groups at 16%, but total distant relapses were lower with induction chemotherapy, 12% versus 20%, over a median follow-up of 64 months.

The work was funded by Cancer Research UK. Dr. McCormack is a consultant for AstraZeneca, Eisai, and GSK, and disclosed honoraria/meeting expenses from Daiicho Sankyo, Roche, and Medscape, the publisher of this article. Among other industry ties, Dr. Tewari is an advisor/consultant, researcher, and speaker for Merck, SeaGen, and AstraZeneca.

Six weeks of induction chemotherapy before definitive chemoradiation for locally advanced cervical cancer substantially improves progression-free and overall survival and should be considered the new standard of care, according to Mary McCormack, MBBS, PhD, a gynecologic and breast oncologist at the University College Hospital, London.

Dr. McCormack was the lead investigator on a phase 3 trial called INTERLACE that tested the approach against stand-alone chemoradiation – the current standard of care – in 500 women, majority in the United Kingdom and Mexico.

She made her comments after presenting the results at the annual meeting of the European Society for Medical Oncology.

The 250 women randomized to induction chemotherapy before chemoradiation (CRT) had a 35% improvement in progression-free survival (PFS), with a 5-year PFS of 73% versus 64% among 250 randomized to CRT alone. Likewise, overall survival (OS) improved 39% in the induction group, with a 5-year OS of 80% versus 72% among women who went straight to CRT.

Induction chemotherapy consisted of 6 weekly doses of carboplatin AUC2 and paclitaxel 80 mg/m² followed by CRT within 7 days. CRT consisted of 5 weekly doses of cisplatin 40 mg/m² plus external beam radiotherapy and brachytherapy. Compliance in both arms was high.

“Induction chemotherapy with weekly paclitaxel and carboplatin delivered immediately before chemoradiotherapy should be considered the new standard in locally advanced cervical cancer, and [it] is feasible across diverse healthcare settings,” Dr. McCormack said.

Study discussant Krishnansu Tewari, MD, a gynecologic oncologist at the University of California, Irvine, was impressed by the results.

“This is the first phase 3 randomized trial in locally advanced cervical cancer that has shown [an overall] survival benefit in over 2 decades. Physicians taking care of these patients could consider induction chemotherapy ... tomorrow morning,” he said.

Dr. Tewari brought up how to incorporate the findings with another trial presented earlier at the meeting, KEYNOTE-A18.

KEYNOTE-A18 added pembrolizumab to CRT, which resulted in substantially better PFS and a strong trend towards better OS that could reach statistical significance with additional follow-up.

Both trials are “practice changing” for locally advanced cervical cancer. “I think we are ready for a paradigm shift,” Dr. Tewari said.

He noted a limit in the INTERLACE presentation was that outcomes were not broken down by tumor stage.

Over three-quarters of the women had stage 2 disease; 9% had stage 1 disease, and only 14% had stage 3B or 4A tumors. Almost 60% of the women were node negative.

It’s unclear at this point if women who have node-negative stage 1B3 or stage 2A-B disease “really need induction chemotherapy. I would think that those patients are probably curable by standard chemoradiation plus brachytherapy, and that the real [benefit would be] for stage 3B and 4A patients,” he said.

The median age in the study was 46 years, and 82% of the women had squamous cell tumors.

Grade 3/4 adverse events were higher in the induction arm, 59% versus 48%, driven mostly by a higher incidence of neutropenia and other hematologic adverse events with induction.

One woman died of adverse events in the induction arm and two died in the CRT-alone arm.

Local and pelvic relapse rates were equal in both groups at 16%, but total distant relapses were lower with induction chemotherapy, 12% versus 20%, over a median follow-up of 64 months.

The work was funded by Cancer Research UK. Dr. McCormack is a consultant for AstraZeneca, Eisai, and GSK, and disclosed honoraria/meeting expenses from Daiicho Sankyo, Roche, and Medscape, the publisher of this article. Among other industry ties, Dr. Tewari is an advisor/consultant, researcher, and speaker for Merck, SeaGen, and AstraZeneca.

Certain products marketed for arthritis and pain management could contain hidden ingredients that could be harmful to consumers, according to a warning by the U.S. Food and Drug Administration.
 

Some of these products contain active ingredients found in anti-inflammatory prescription medication.

“These products may cause potentially serious side effects and may interact with medications or dietary supplements a consumer is taking,” the FDA said in a statement. “It is clear from the results of our decade of testing that retailers and distributors, including online marketplaces, do not effectively prevent these types of potentially harmful products from being sold to consumers.”

Unlike prescription medication and over-the-counter drugs such as loratadine (Claritin) or acetaminophen (Tylenol), supplements do not need FDA approval before they can be sold. Only after a complaint is made or FDA testing reveals illegal or unsafe ingredients can the FDA get involved.

From August 2013 to September 2023, the FDA identified 22 arthritis and pain products with active ingredients not disclosed on the product label. The most common hidden ingredients detected in these supplements were prescription-only corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants, said Candy Tsourounis, PharmD, a professor in the department of clinical pharmacy at the University of California, San Francisco.

Kuka Flex Forte and Reumo Flex, both promoted for joint pain and arthritis, both contain the NSAID diclofenac. Tapee Tea, a product promoted for pain relief, contains dexamethasone and piroxicam. AK Forte, also sold for joint pain and arthritis, contains diclofenac, dexamethasone, and methocarbamol not disclosed on the label.

“It is interesting that these products have hidden ingredients that are used to reduce swelling and inflammation,” Dr. Tsourounis said. “I don’t know if this was intentional, but it seems suspicious that a product marketed to reduce joint pain and inflammation contains prescription-only ingredients that are used for this purpose.”

Certain products also contained antihistamines including cyproheptadine and chlorpheniramine.

These types of products are likely targeted toward underserved and immigrant communities, added Pieter Cohen, MD, a primary care physician and an assistant professor of medicine at Harvard Medical School, Boston, who studies dietary supplements. They might be sold in mom-and-pop shops or gas stations to individuals with limited access to health care or insurance, he noted.

The FDA warned that this list included “only a small fraction of the potentially dangerous products marketed to consumers online and in stores. Even if a product is not included in this list, consumers should exercise caution before using these types of arthritis and pain management products.”
 

Advising patients

Research suggests that most patients do not tell doctors about the supplements they are taking, and often, clinicians do not ask, said Dr. Cohen. “Most of the time it’s a total black box – we don’t know what’s going on,” he added.

He advised raising the subject of supplements in a very nonjudgmental way, particularly when treating patients in marginalized and immigrant communities. One approach he suggested was first mentioning that other patients in your care dealing with joint pain have bought remedies locally or have tried treatments that friends recommend. You can then ask a patient about their own use, framing it as a way to better help with treatment decisions.

Once a clinician understands what their patient is taking, they can then give advice and discuss if a product is safe to combine with prescription drugs, Dr. Cohen said. “If they come down too hard, I think the patients will just clam up and not talk about it anymore,” he said.

If a patient begins to experience side effects or gets sick, a clinician will already be informed of what their patient is taking and can ask that patient to bring the product or supplement in, so they can look over the product together, Dr. Cohen noted. Any side effects or other adverse events potentially related to the use of these products should then be reported to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
 

Tips for safe shopping

To make sure supplements and other over-the-counter products are safe to use, Dr. Tsourounis recommends that consumers:

• Buy products from well-known retailers like Target or large pharmacies like CVS or Walgreens.
• Avoid buying products with labels in another language that you cannot read or products with no drug label.
• Be cautious of buying products online or from other countries.
• Look up suspicious products on the FDA’s health fraud database.
• Be wary of any product that offers miracle cures or relies on personal testimonies without evidence.

In general, do not base purchasing decisions on any health claims on a product label because companies selling supplements making these claims “don’t have to have any clinical data to back them up,” Dr. Cohen said.

Dr. Cohen also recommends sticking with individual ingredients. “If you want echinacea, buy echinacea. Don’t buy a complicated mix that is supposed to be good for arthritis with 10 different botanical [ingredients]. That’s more likely to run [you] into trouble,” he said.

Last, Dr. Cohen recommended buying supplements that are certified by NSF International or United States Pharmacopeia, both respected third-party testing organizations. “If it has an NSF International or USP stamp, that gives us more certainty that what’s in the bottle is going to be what’s listed on label,” he said.

Dr. Tsourounis noted that if you are skeptical of a product, you can also try calling the manufacturer number on the product label.

“I always encourage people to call that number to see if somebody answers,” she said. “Sometimes, you can tell a lot about that company just by calling that number.”

Dr. Cohen has received research support from the Consumers Union and PEW Charitable Trusts and royalties from UpToDate. He has collaborated in research with NSF International. Dr. Tsourounis disclosed no relevant financial relationships.

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

Certain products marketed for arthritis and pain management could contain hidden ingredients that could be harmful to consumers, according to a warning by the U.S. Food and Drug Administration.
 

Some of these products contain active ingredients found in anti-inflammatory prescription medication.

“These products may cause potentially serious side effects and may interact with medications or dietary supplements a consumer is taking,” the FDA said in a statement. “It is clear from the results of our decade of testing that retailers and distributors, including online marketplaces, do not effectively prevent these types of potentially harmful products from being sold to consumers.”

Unlike prescription medication and over-the-counter drugs such as loratadine (Claritin) or acetaminophen (Tylenol), supplements do not need FDA approval before they can be sold. Only after a complaint is made or FDA testing reveals illegal or unsafe ingredients can the FDA get involved.

From August 2013 to September 2023, the FDA identified 22 arthritis and pain products with active ingredients not disclosed on the product label. The most common hidden ingredients detected in these supplements were prescription-only corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants, said Candy Tsourounis, PharmD, a professor in the department of clinical pharmacy at the University of California, San Francisco.

Kuka Flex Forte and Reumo Flex, both promoted for joint pain and arthritis, both contain the NSAID diclofenac. Tapee Tea, a product promoted for pain relief, contains dexamethasone and piroxicam. AK Forte, also sold for joint pain and arthritis, contains diclofenac, dexamethasone, and methocarbamol not disclosed on the label.

“It is interesting that these products have hidden ingredients that are used to reduce swelling and inflammation,” Dr. Tsourounis said. “I don’t know if this was intentional, but it seems suspicious that a product marketed to reduce joint pain and inflammation contains prescription-only ingredients that are used for this purpose.”

Certain products also contained antihistamines including cyproheptadine and chlorpheniramine.

These types of products are likely targeted toward underserved and immigrant communities, added Pieter Cohen, MD, a primary care physician and an assistant professor of medicine at Harvard Medical School, Boston, who studies dietary supplements. They might be sold in mom-and-pop shops or gas stations to individuals with limited access to health care or insurance, he noted.

The FDA warned that this list included “only a small fraction of the potentially dangerous products marketed to consumers online and in stores. Even if a product is not included in this list, consumers should exercise caution before using these types of arthritis and pain management products.”
 

Advising patients

Research suggests that most patients do not tell doctors about the supplements they are taking, and often, clinicians do not ask, said Dr. Cohen. “Most of the time it’s a total black box – we don’t know what’s going on,” he added.

He advised raising the subject of supplements in a very nonjudgmental way, particularly when treating patients in marginalized and immigrant communities. One approach he suggested was first mentioning that other patients in your care dealing with joint pain have bought remedies locally or have tried treatments that friends recommend. You can then ask a patient about their own use, framing it as a way to better help with treatment decisions.

Once a clinician understands what their patient is taking, they can then give advice and discuss if a product is safe to combine with prescription drugs, Dr. Cohen said. “If they come down too hard, I think the patients will just clam up and not talk about it anymore,” he said.

If a patient begins to experience side effects or gets sick, a clinician will already be informed of what their patient is taking and can ask that patient to bring the product or supplement in, so they can look over the product together, Dr. Cohen noted. Any side effects or other adverse events potentially related to the use of these products should then be reported to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
 

Tips for safe shopping

To make sure supplements and other over-the-counter products are safe to use, Dr. Tsourounis recommends that consumers:

• Buy products from well-known retailers like Target or large pharmacies like CVS or Walgreens.
• Avoid buying products with labels in another language that you cannot read or products with no drug label.
• Be cautious of buying products online or from other countries.
• Look up suspicious products on the FDA’s health fraud database.
• Be wary of any product that offers miracle cures or relies on personal testimonies without evidence.

In general, do not base purchasing decisions on any health claims on a product label because companies selling supplements making these claims “don’t have to have any clinical data to back them up,” Dr. Cohen said.

Dr. Cohen also recommends sticking with individual ingredients. “If you want echinacea, buy echinacea. Don’t buy a complicated mix that is supposed to be good for arthritis with 10 different botanical [ingredients]. That’s more likely to run [you] into trouble,” he said.

Last, Dr. Cohen recommended buying supplements that are certified by NSF International or United States Pharmacopeia, both respected third-party testing organizations. “If it has an NSF International or USP stamp, that gives us more certainty that what’s in the bottle is going to be what’s listed on label,” he said.

Dr. Tsourounis noted that if you are skeptical of a product, you can also try calling the manufacturer number on the product label.

“I always encourage people to call that number to see if somebody answers,” she said. “Sometimes, you can tell a lot about that company just by calling that number.”

Dr. Cohen has received research support from the Consumers Union and PEW Charitable Trusts and royalties from UpToDate. He has collaborated in research with NSF International. Dr. Tsourounis disclosed no relevant financial relationships.

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

Certain products marketed for arthritis and pain management could contain hidden ingredients that could be harmful to consumers, according to a warning by the U.S. Food and Drug Administration.
 

Some of these products contain active ingredients found in anti-inflammatory prescription medication.

“These products may cause potentially serious side effects and may interact with medications or dietary supplements a consumer is taking,” the FDA said in a statement. “It is clear from the results of our decade of testing that retailers and distributors, including online marketplaces, do not effectively prevent these types of potentially harmful products from being sold to consumers.”

Unlike prescription medication and over-the-counter drugs such as loratadine (Claritin) or acetaminophen (Tylenol), supplements do not need FDA approval before they can be sold. Only after a complaint is made or FDA testing reveals illegal or unsafe ingredients can the FDA get involved.

From August 2013 to September 2023, the FDA identified 22 arthritis and pain products with active ingredients not disclosed on the product label. The most common hidden ingredients detected in these supplements were prescription-only corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants, said Candy Tsourounis, PharmD, a professor in the department of clinical pharmacy at the University of California, San Francisco.

Kuka Flex Forte and Reumo Flex, both promoted for joint pain and arthritis, both contain the NSAID diclofenac. Tapee Tea, a product promoted for pain relief, contains dexamethasone and piroxicam. AK Forte, also sold for joint pain and arthritis, contains diclofenac, dexamethasone, and methocarbamol not disclosed on the label.

“It is interesting that these products have hidden ingredients that are used to reduce swelling and inflammation,” Dr. Tsourounis said. “I don’t know if this was intentional, but it seems suspicious that a product marketed to reduce joint pain and inflammation contains prescription-only ingredients that are used for this purpose.”

Certain products also contained antihistamines including cyproheptadine and chlorpheniramine.

These types of products are likely targeted toward underserved and immigrant communities, added Pieter Cohen, MD, a primary care physician and an assistant professor of medicine at Harvard Medical School, Boston, who studies dietary supplements. They might be sold in mom-and-pop shops or gas stations to individuals with limited access to health care or insurance, he noted.

The FDA warned that this list included “only a small fraction of the potentially dangerous products marketed to consumers online and in stores. Even if a product is not included in this list, consumers should exercise caution before using these types of arthritis and pain management products.”
 

Advising patients

Research suggests that most patients do not tell doctors about the supplements they are taking, and often, clinicians do not ask, said Dr. Cohen. “Most of the time it’s a total black box – we don’t know what’s going on,” he added.

He advised raising the subject of supplements in a very nonjudgmental way, particularly when treating patients in marginalized and immigrant communities. One approach he suggested was first mentioning that other patients in your care dealing with joint pain have bought remedies locally or have tried treatments that friends recommend. You can then ask a patient about their own use, framing it as a way to better help with treatment decisions.

Once a clinician understands what their patient is taking, they can then give advice and discuss if a product is safe to combine with prescription drugs, Dr. Cohen said. “If they come down too hard, I think the patients will just clam up and not talk about it anymore,” he said.

If a patient begins to experience side effects or gets sick, a clinician will already be informed of what their patient is taking and can ask that patient to bring the product or supplement in, so they can look over the product together, Dr. Cohen noted. Any side effects or other adverse events potentially related to the use of these products should then be reported to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
 

Tips for safe shopping

To make sure supplements and other over-the-counter products are safe to use, Dr. Tsourounis recommends that consumers:

• Buy products from well-known retailers like Target or large pharmacies like CVS or Walgreens.
• Avoid buying products with labels in another language that you cannot read or products with no drug label.
• Be cautious of buying products online or from other countries.
• Look up suspicious products on the FDA’s health fraud database.
• Be wary of any product that offers miracle cures or relies on personal testimonies without evidence.

In general, do not base purchasing decisions on any health claims on a product label because companies selling supplements making these claims “don’t have to have any clinical data to back them up,” Dr. Cohen said.

Dr. Cohen also recommends sticking with individual ingredients. “If you want echinacea, buy echinacea. Don’t buy a complicated mix that is supposed to be good for arthritis with 10 different botanical [ingredients]. That’s more likely to run [you] into trouble,” he said.

Last, Dr. Cohen recommended buying supplements that are certified by NSF International or United States Pharmacopeia, both respected third-party testing organizations. “If it has an NSF International or USP stamp, that gives us more certainty that what’s in the bottle is going to be what’s listed on label,” he said.

Dr. Tsourounis noted that if you are skeptical of a product, you can also try calling the manufacturer number on the product label.

“I always encourage people to call that number to see if somebody answers,” she said. “Sometimes, you can tell a lot about that company just by calling that number.”

Dr. Cohen has received research support from the Consumers Union and PEW Charitable Trusts and royalties from UpToDate. He has collaborated in research with NSF International. Dr. Tsourounis disclosed no relevant financial relationships.

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

A type of B-cell lymphoma called early-stage I primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) has highly favorable survival rates, according to new research presented at the European Society of Medical Oncology (ESMO) Congress 2023. While relapse is common, those rates are significantly lower with radiation therapy.

“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.

Dr. Gao presented these findings at ESMO 2023, held in Madrid.

“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”

POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.

Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.

“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.

To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.

Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.

Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.

With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.

Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.

The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).

In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.

“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.

Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).

The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).

However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.

Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.

Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.

Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.

In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.

“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.

“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.

“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”

Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”


 

Benefits linked to radiation therapy dose?

Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.

“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.

The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”

He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”

Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”

The authors had no disclosures to report.

A type of B-cell lymphoma called early-stage I primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) has highly favorable survival rates, according to new research presented at the European Society of Medical Oncology (ESMO) Congress 2023. While relapse is common, those rates are significantly lower with radiation therapy.

“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.

Dr. Gao presented these findings at ESMO 2023, held in Madrid.

“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”

POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.

Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.

“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.

To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.

Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.

Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.

With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.

Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.

The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).

In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.

“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.

Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).

The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).

However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.

Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.

Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.

Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.

In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.

“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.

“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.

“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”

Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”


 

Benefits linked to radiation therapy dose?

Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.

“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.

The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”

He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”

Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”

The authors had no disclosures to report.

A type of B-cell lymphoma called early-stage I primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) has highly favorable survival rates, according to new research presented at the European Society of Medical Oncology (ESMO) Congress 2023. While relapse is common, those rates are significantly lower with radiation therapy.

“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.

Dr. Gao presented these findings at ESMO 2023, held in Madrid.

“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”

POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.

Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.

“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.

To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.

Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.

Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.

With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.

Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.

The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).

In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.

“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.

Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).

The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).

However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.

Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.

Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.

Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.

In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.

“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.

“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.

“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”

Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”


 

Benefits linked to radiation therapy dose?

Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.

“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.

The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”

He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”

Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”

The authors had no disclosures to report.

Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers. 

A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?

Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery. 

“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.

Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care. 

“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”

With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
 

Not so fast in the United States

In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal. 

Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.

“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”

States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.

But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.

Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.

The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.

For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.

This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.

“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease. 

For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors. 

A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.

Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said. 
 

Changes in the United States

The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases. 

The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.

But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said. 

“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”

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

Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers. 

A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?

Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery. 

“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.

Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care. 

“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”

With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
 

Not so fast in the United States

In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal. 

Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.

“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”

States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.

But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.

Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.

The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.

For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.

This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.

“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease. 

For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors. 

A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.

Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said. 
 

Changes in the United States

The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases. 

The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.

But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said. 

“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”

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

Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers. 

A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?

Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery.