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A high-fiber diet may improve treatment response among patients with advanced melanoma receiving immune checkpoint inhibitors, while probiotics may reduce treatment effectiveness, a new study shows.

Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.

And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.

“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”

Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.

Still, the role diet and probiotic supplements play in treatment response remains poorly understood.

In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.

In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).

Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).

The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.

“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.

When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.

Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.

According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”

Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.

However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”

While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.

Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.

Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.

This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.

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

A high-fiber diet may improve treatment response among patients with advanced melanoma receiving immune checkpoint inhibitors, while probiotics may reduce treatment effectiveness, a new study shows.

Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.

And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.

“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”

Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.

Still, the role diet and probiotic supplements play in treatment response remains poorly understood.

In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.

In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).

Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).

The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.

“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.

When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.

Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.

According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”

Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.

However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”

While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.

Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.

Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.

This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.

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

A high-fiber diet may improve treatment response among patients with advanced melanoma receiving immune checkpoint inhibitors, while probiotics may reduce treatment effectiveness, a new study shows.

Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.

And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.

“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”

Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.

Still, the role diet and probiotic supplements play in treatment response remains poorly understood.

In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.

In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).

Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).

The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.

“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.

When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.

Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.

According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”

Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.

However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”

While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.

Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.

Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.

This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.

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

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) has lowered the recommended age to start CRC screening from 50 to 45 years of age for all average-risk individuals.

Although no studies have directly demonstrated the result of lowering the age of screening, lead author Swati G. Patel, MD, of University of Colorado Anschutz Medical Center, Aurora, and colleagues suggested that the increasing incidence of advanced CRC among younger individuals, coupled with the net benefit of screening, warrant a lower age threshold.

“Recent data ... show that CRC incidence rates in individuals ages 50 to 64 have increased by 1% annually between 2011 and 2016,” the authors wrote in Gastroenterology. “Similarly, CRC incidence and mortality rates in persons under age 50, termed early-age onset CRC (EAO-CRC), are also increasing.”

The task force of nine experts, representing the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, conducted a literature review and generated recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition to recommending a lower age for initial screening, Dr. Patel and colleagues provided guidance for cessation of screening among older individuals.
 

Guidance for screening initiation

According to the authors, the present risk of CRC among younger individuals mirrors the historical risk for older individuals before screening was prevalent.

“The current CRC incidence rates in individuals ages 45 to 49 are similar to the incidence rates observed in 50-year-olds in 1992, before widespread CRC screening was performed,” they wrote.

Elevated rates among younger people have been disproportionately driven by rectal cancer, according to the authors. From 2006 to 2015, incidence of rectal cancer among Americans under 50 increased 1.7% per year, compared with 0.7% per year for colon cancer, based on data from the North American Association of Central Cancer Registries.

Associated mortality rates also increased, the authors noted. From 1999-2019, mortality from colon cancer among people 45-49 years increased from 6.4 to 6.6 deaths per 100,000 individuals, while deaths from rectal cancer increased from 1.3 to 1.7 per 100,000, according to the CDC. Concurrently, CRC-associated mortality rates among older individuals generally declined.

While these findings suggest a growing disease burden among the under-50-year age group, controlled data demonstrating the effects of earlier screening are lacking, Dr. Patel and colleagues noted. Still, they predicted that expanded screening would generate a net benefit.

“Although there are no CRC screening safety data for average-risk individuals [younger than] 50, there are ample data that colonoscopy for other indications (screening based on family history, symptom evaluation, etc.) is safer when comparing younger versus older individuals,” they wrote.

Supporting this claim, the authors cited three independently generated microsimulation models from the Agency for Healthcare Research and Quality that “showed a favorable balance of life-years gained compared with adverse events,” given 100% compliance.
 

Guidance for screening cessation

Like the situation with younger individuals, minimal data are available to determine the best time for screening cessation, according to the task force.

“There are no randomized or observational studies after 2017 that enrolled individuals over age 75 to inform the appropriate time to stop CRC screening,” the authors wrote. “In our search of 37 relevant articles, only one presented primary data for when to stop screening.”

This one available study showed that some individuals older than 74 do in fact gain benefit from screening,

“For example,” Dr. Patel and colleagues wrote, “women without a history of screening and no comorbidities benefitted from annual fecal immunochemical test (FIT) screening until age 90, whereas unscreened men with or without comorbidities benefited from annual FIT screening until age 88. Conversely, screening was not beneficial beyond age 66 in men or women with severe comorbidities.”

The task force therefore recommended personalized screening for individuals 76-85 years of age “based on the balance of benefits and harms and individual patient clinical factors and preferences.”

Screening for individuals 86 years and older, according to the task force, is unnecessary.

The authors disclosed relationships with Olympus America, Bayer Pharmaceuticals, Janssen Pharmaceuticals, and others.

This article was updated on Jan. 3, 2022.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) has lowered the recommended age to start CRC screening from 50 to 45 years of age for all average-risk individuals.

Although no studies have directly demonstrated the result of lowering the age of screening, lead author Swati G. Patel, MD, of University of Colorado Anschutz Medical Center, Aurora, and colleagues suggested that the increasing incidence of advanced CRC among younger individuals, coupled with the net benefit of screening, warrant a lower age threshold.

“Recent data ... show that CRC incidence rates in individuals ages 50 to 64 have increased by 1% annually between 2011 and 2016,” the authors wrote in Gastroenterology. “Similarly, CRC incidence and mortality rates in persons under age 50, termed early-age onset CRC (EAO-CRC), are also increasing.”

The task force of nine experts, representing the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, conducted a literature review and generated recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition to recommending a lower age for initial screening, Dr. Patel and colleagues provided guidance for cessation of screening among older individuals.
 

Guidance for screening initiation

According to the authors, the present risk of CRC among younger individuals mirrors the historical risk for older individuals before screening was prevalent.

“The current CRC incidence rates in individuals ages 45 to 49 are similar to the incidence rates observed in 50-year-olds in 1992, before widespread CRC screening was performed,” they wrote.

Elevated rates among younger people have been disproportionately driven by rectal cancer, according to the authors. From 2006 to 2015, incidence of rectal cancer among Americans under 50 increased 1.7% per year, compared with 0.7% per year for colon cancer, based on data from the North American Association of Central Cancer Registries.

Associated mortality rates also increased, the authors noted. From 1999-2019, mortality from colon cancer among people 45-49 years increased from 6.4 to 6.6 deaths per 100,000 individuals, while deaths from rectal cancer increased from 1.3 to 1.7 per 100,000, according to the CDC. Concurrently, CRC-associated mortality rates among older individuals generally declined.

While these findings suggest a growing disease burden among the under-50-year age group, controlled data demonstrating the effects of earlier screening are lacking, Dr. Patel and colleagues noted. Still, they predicted that expanded screening would generate a net benefit.

“Although there are no CRC screening safety data for average-risk individuals [younger than] 50, there are ample data that colonoscopy for other indications (screening based on family history, symptom evaluation, etc.) is safer when comparing younger versus older individuals,” they wrote.

Supporting this claim, the authors cited three independently generated microsimulation models from the Agency for Healthcare Research and Quality that “showed a favorable balance of life-years gained compared with adverse events,” given 100% compliance.
 

Guidance for screening cessation

Like the situation with younger individuals, minimal data are available to determine the best time for screening cessation, according to the task force.

“There are no randomized or observational studies after 2017 that enrolled individuals over age 75 to inform the appropriate time to stop CRC screening,” the authors wrote. “In our search of 37 relevant articles, only one presented primary data for when to stop screening.”

This one available study showed that some individuals older than 74 do in fact gain benefit from screening,

“For example,” Dr. Patel and colleagues wrote, “women without a history of screening and no comorbidities benefitted from annual fecal immunochemical test (FIT) screening until age 90, whereas unscreened men with or without comorbidities benefited from annual FIT screening until age 88. Conversely, screening was not beneficial beyond age 66 in men or women with severe comorbidities.”

The task force therefore recommended personalized screening for individuals 76-85 years of age “based on the balance of benefits and harms and individual patient clinical factors and preferences.”

Screening for individuals 86 years and older, according to the task force, is unnecessary.

The authors disclosed relationships with Olympus America, Bayer Pharmaceuticals, Janssen Pharmaceuticals, and others.

This article was updated on Jan. 3, 2022.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) has lowered the recommended age to start CRC screening from 50 to 45 years of age for all average-risk individuals.

Although no studies have directly demonstrated the result of lowering the age of screening, lead author Swati G. Patel, MD, of University of Colorado Anschutz Medical Center, Aurora, and colleagues suggested that the increasing incidence of advanced CRC among younger individuals, coupled with the net benefit of screening, warrant a lower age threshold.

“Recent data ... show that CRC incidence rates in individuals ages 50 to 64 have increased by 1% annually between 2011 and 2016,” the authors wrote in Gastroenterology. “Similarly, CRC incidence and mortality rates in persons under age 50, termed early-age onset CRC (EAO-CRC), are also increasing.”

The task force of nine experts, representing the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, conducted a literature review and generated recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition to recommending a lower age for initial screening, Dr. Patel and colleagues provided guidance for cessation of screening among older individuals.
 

Guidance for screening initiation

According to the authors, the present risk of CRC among younger individuals mirrors the historical risk for older individuals before screening was prevalent.

“The current CRC incidence rates in individuals ages 45 to 49 are similar to the incidence rates observed in 50-year-olds in 1992, before widespread CRC screening was performed,” they wrote.

Elevated rates among younger people have been disproportionately driven by rectal cancer, according to the authors. From 2006 to 2015, incidence of rectal cancer among Americans under 50 increased 1.7% per year, compared with 0.7% per year for colon cancer, based on data from the North American Association of Central Cancer Registries.

Associated mortality rates also increased, the authors noted. From 1999-2019, mortality from colon cancer among people 45-49 years increased from 6.4 to 6.6 deaths per 100,000 individuals, while deaths from rectal cancer increased from 1.3 to 1.7 per 100,000, according to the CDC. Concurrently, CRC-associated mortality rates among older individuals generally declined.

While these findings suggest a growing disease burden among the under-50-year age group, controlled data demonstrating the effects of earlier screening are lacking, Dr. Patel and colleagues noted. Still, they predicted that expanded screening would generate a net benefit.

“Although there are no CRC screening safety data for average-risk individuals [younger than] 50, there are ample data that colonoscopy for other indications (screening based on family history, symptom evaluation, etc.) is safer when comparing younger versus older individuals,” they wrote.

Supporting this claim, the authors cited three independently generated microsimulation models from the Agency for Healthcare Research and Quality that “showed a favorable balance of life-years gained compared with adverse events,” given 100% compliance.
 

Guidance for screening cessation

Like the situation with younger individuals, minimal data are available to determine the best time for screening cessation, according to the task force.

“There are no randomized or observational studies after 2017 that enrolled individuals over age 75 to inform the appropriate time to stop CRC screening,” the authors wrote. “In our search of 37 relevant articles, only one presented primary data for when to stop screening.”

This one available study showed that some individuals older than 74 do in fact gain benefit from screening,

“For example,” Dr. Patel and colleagues wrote, “women without a history of screening and no comorbidities benefitted from annual fecal immunochemical test (FIT) screening until age 90, whereas unscreened men with or without comorbidities benefited from annual FIT screening until age 88. Conversely, screening was not beneficial beyond age 66 in men or women with severe comorbidities.”

The task force therefore recommended personalized screening for individuals 76-85 years of age “based on the balance of benefits and harms and individual patient clinical factors and preferences.”

Screening for individuals 86 years and older, according to the task force, is unnecessary.

The authors disclosed relationships with Olympus America, Bayer Pharmaceuticals, Janssen Pharmaceuticals, and others.

This article was updated on Jan. 3, 2022.

SAN ANTONIO – In a large prospective, international cohort, food additive nitrates and nitrites, artificial sweeteners (especially aspartame and acesulfame-K), and dietary trans fatty acids were found to be associated with increased cancer risks.

The findings were reported in three poster presentations (P1-09-01, P1-09-02 and P3-12-35) at the 2021 San Antonio Breast Cancer Symposium from the ongoing French NutriNet-Santé web-based study of 171,000 people that was launched in France in 2009 to investigate nutrition and health relationships. The authors of the analyses note that while evidence of deleterious health effects has been established for the dietary focus of their studies, and cancer risks have been suspected, strong evidence of a cancer association has been lacking.

Nitrates and nitrites are used in processed meats to increase shelf life and to avoid bacterial growth, said Eloi Chazelas, PhD, Nutritional Epidemiology Research Team (EREN) at Sorbonne Paris Nord University. Dr. Chazelas looked at consumption of nitrites and nitrates through repeated 24 hour dietary records, linked to a comprehensive food composition database. The study’s main outcome measure was adjusted associations between nitrite and nitrate exposures and the risk of cancer (overall and by main cancer sites).

During follow-up, 966 breast and 400 prostate cancers were diagnosed among 3,311 first incident cancer cases. Breast cancer risk was elevated (HR = 1.24 [1.03-1.48], P = 0.02) among higher consumers of nitrates from food additives, especially with potassium nitrate consumption (HR = 1.25 [1.04-1.50], P = 0.01). Elevated prostate cancer risk was associated with nitrites (HR = 1.58 [1.14-2.18], P = 0.008), specifically for sodium nitrite (HR = 1.62 [1.17-2.25], P = 0.004). Nitrates and nitrites from natural sources were not associated significantly with higher cancer risk, Dr. Chazelas said.

He and his team found that food additive nitrates were positively associated with breast cancer risk, and food additive nitrites were positively associated with prostate cancer risk. “While these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of nitrite additives in the food industry,” said Dr. Chazelas, who is a doctoral candidate at Sorbonne Paris Nord University.

In “Breast and prostate cancer risk associated with nitrites and nitrates from food additives (P1-09-01),” the study included 102,046 adults from the French NutriNet-Santé prospective cohort (2009-2021). It examined associations between artificial sweetener intakes (total from all dietary sources, the most frequently consumed ones [aspartame e951, acesulfame-K e950 and sucralose e955]) and cancer risk (overall and by sites: breast, prostate and obesity-related cancers).

Overall cancer risk in people who consumed higher amounts of total sweeteners (i.e. above the median exposure in consumers) was elevated (n = 2,527 cases, hazard ratio = 1.12, 95 percent confidence interval = 1.00-1.25, P-trend=0.005), especially for aspartame (HR = 1.20 [1.05-1.38] P = 0.001) and acesulfame-K (HR = 1.18 [1.04-1.34] P = 0.003). Elevated breast cancer risks (among 723 cases) were observed for total sweeteners (HR = 1.25 [1.02-1.53] P = 0.01), for aspartame (HR = 1.33 [1.05-1.69] P = 0.007), and for acesulfame-K (HR = 1.39 [1.11-1.74] P = 0.003). Also, obesity-related cancers (1,509 cases) were increased for total sweeteners (HR = 1.16 [1.00-1.33] P = 0.02), for aspartame (HR = 1.22 [1.02-1.45] P = 0.01) and for acesulfame-K (HR = 1.23 [1.04-1.45] P = 0.01).

Artificial sweeteners are found in more than 10,000 foods and beverages, said Charlotte Debras, a doctoral candidate in nutritional epidemiology at Sorbonne Paris Nord University. “These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally,” she said.
 

Trans fatty acid intakes and cancer risk

Investigating associations between trans fatty acid intake (total ruminant [rTFAs], industrial [iTFAs], and corresponding specific isomers and cancer risk), the analysis of Gaëlle Wendeu-Foyet, PhD, Sorbonne Paris Nord University, found a total of 3,374 incident cancer cases (982 breast, 405 prostate) in an overall population of 104,909. Dietary intake of total TFAs was associated with higher prostate cancer risk (hazard ration for quartile 4 versus 1: 1.27, 1.11-1.77 P-trend = 0.005). Also, rTFAs were associated with increased overall cancer risk (1.16, 1.02-1.32 P-trend = 0.07), in particular the conjugated linoleic acid isomers (CLA) (1.19, 1.04-1.36 P-trend = 0.04). These associations were specifically observed for breast cancer (rTFAs: 1.35, 1.06-1.72 P-trend = 0.01; CLA: 1.29, 1.00-1.66 P-trend = 0.048), in particular before menopause (rTFAs: 1.68, 1.06-2.67 P-trend = 0.02; CLA: 2.013, 1.25-3.23 P-trend = 0.003). Several iTFAs were associated with overall (1.18, 1.06-1.31 P-trend = 0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30, 1.06-1.58 P-trend = 0.01; hexadecenoic acid: 1.28, 1.05-1.56 P-trend = 0.02) and prostate (transdocosenoic acid: 1.52, 1.09-2.12 P-trend = 0.07) cancer risks.

“These results support the WHO’s goal of achieving elimination from food supplies of industrially produced TFAs,” Dr. Foyet said. “The consumption of food products containing partially hydrogenated oils should be avoided.”

Nutrition, along with avoiding tobacco intake, is one of the main modifiable risk factors for chronic diseases. “There is a lot at stake in terms of prevention. This requires a combination of actions at the individual level to the public level by informing the public through food labeling,” Ms. Debras said.

It also requires influencing the context in which citizens evolve by encouraging manufacturers to improve their products (pricing policies, commitment charters for product reformulation, etc.), and limiting advertising and marketing for products of poor nutritional quality (especially among children),” she said.

SAN ANTONIO – In a large prospective, international cohort, food additive nitrates and nitrites, artificial sweeteners (especially aspartame and acesulfame-K), and dietary trans fatty acids were found to be associated with increased cancer risks.

The findings were reported in three poster presentations (P1-09-01, P1-09-02 and P3-12-35) at the 2021 San Antonio Breast Cancer Symposium from the ongoing French NutriNet-Santé web-based study of 171,000 people that was launched in France in 2009 to investigate nutrition and health relationships. The authors of the analyses note that while evidence of deleterious health effects has been established for the dietary focus of their studies, and cancer risks have been suspected, strong evidence of a cancer association has been lacking.

Nitrates and nitrites are used in processed meats to increase shelf life and to avoid bacterial growth, said Eloi Chazelas, PhD, Nutritional Epidemiology Research Team (EREN) at Sorbonne Paris Nord University. Dr. Chazelas looked at consumption of nitrites and nitrates through repeated 24 hour dietary records, linked to a comprehensive food composition database. The study’s main outcome measure was adjusted associations between nitrite and nitrate exposures and the risk of cancer (overall and by main cancer sites).

During follow-up, 966 breast and 400 prostate cancers were diagnosed among 3,311 first incident cancer cases. Breast cancer risk was elevated (HR = 1.24 [1.03-1.48], P = 0.02) among higher consumers of nitrates from food additives, especially with potassium nitrate consumption (HR = 1.25 [1.04-1.50], P = 0.01). Elevated prostate cancer risk was associated with nitrites (HR = 1.58 [1.14-2.18], P = 0.008), specifically for sodium nitrite (HR = 1.62 [1.17-2.25], P = 0.004). Nitrates and nitrites from natural sources were not associated significantly with higher cancer risk, Dr. Chazelas said.

He and his team found that food additive nitrates were positively associated with breast cancer risk, and food additive nitrites were positively associated with prostate cancer risk. “While these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of nitrite additives in the food industry,” said Dr. Chazelas, who is a doctoral candidate at Sorbonne Paris Nord University.

In “Breast and prostate cancer risk associated with nitrites and nitrates from food additives (P1-09-01),” the study included 102,046 adults from the French NutriNet-Santé prospective cohort (2009-2021). It examined associations between artificial sweetener intakes (total from all dietary sources, the most frequently consumed ones [aspartame e951, acesulfame-K e950 and sucralose e955]) and cancer risk (overall and by sites: breast, prostate and obesity-related cancers).

Overall cancer risk in people who consumed higher amounts of total sweeteners (i.e. above the median exposure in consumers) was elevated (n = 2,527 cases, hazard ratio = 1.12, 95 percent confidence interval = 1.00-1.25, P-trend=0.005), especially for aspartame (HR = 1.20 [1.05-1.38] P = 0.001) and acesulfame-K (HR = 1.18 [1.04-1.34] P = 0.003). Elevated breast cancer risks (among 723 cases) were observed for total sweeteners (HR = 1.25 [1.02-1.53] P = 0.01), for aspartame (HR = 1.33 [1.05-1.69] P = 0.007), and for acesulfame-K (HR = 1.39 [1.11-1.74] P = 0.003). Also, obesity-related cancers (1,509 cases) were increased for total sweeteners (HR = 1.16 [1.00-1.33] P = 0.02), for aspartame (HR = 1.22 [1.02-1.45] P = 0.01) and for acesulfame-K (HR = 1.23 [1.04-1.45] P = 0.01).

Artificial sweeteners are found in more than 10,000 foods and beverages, said Charlotte Debras, a doctoral candidate in nutritional epidemiology at Sorbonne Paris Nord University. “These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally,” she said.
 

Trans fatty acid intakes and cancer risk

Investigating associations between trans fatty acid intake (total ruminant [rTFAs], industrial [iTFAs], and corresponding specific isomers and cancer risk), the analysis of Gaëlle Wendeu-Foyet, PhD, Sorbonne Paris Nord University, found a total of 3,374 incident cancer cases (982 breast, 405 prostate) in an overall population of 104,909. Dietary intake of total TFAs was associated with higher prostate cancer risk (hazard ration for quartile 4 versus 1: 1.27, 1.11-1.77 P-trend = 0.005). Also, rTFAs were associated with increased overall cancer risk (1.16, 1.02-1.32 P-trend = 0.07), in particular the conjugated linoleic acid isomers (CLA) (1.19, 1.04-1.36 P-trend = 0.04). These associations were specifically observed for breast cancer (rTFAs: 1.35, 1.06-1.72 P-trend = 0.01; CLA: 1.29, 1.00-1.66 P-trend = 0.048), in particular before menopause (rTFAs: 1.68, 1.06-2.67 P-trend = 0.02; CLA: 2.013, 1.25-3.23 P-trend = 0.003). Several iTFAs were associated with overall (1.18, 1.06-1.31 P-trend = 0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30, 1.06-1.58 P-trend = 0.01; hexadecenoic acid: 1.28, 1.05-1.56 P-trend = 0.02) and prostate (transdocosenoic acid: 1.52, 1.09-2.12 P-trend = 0.07) cancer risks.

“These results support the WHO’s goal of achieving elimination from food supplies of industrially produced TFAs,” Dr. Foyet said. “The consumption of food products containing partially hydrogenated oils should be avoided.”

Nutrition, along with avoiding tobacco intake, is one of the main modifiable risk factors for chronic diseases. “There is a lot at stake in terms of prevention. This requires a combination of actions at the individual level to the public level by informing the public through food labeling,” Ms. Debras said.

It also requires influencing the context in which citizens evolve by encouraging manufacturers to improve their products (pricing policies, commitment charters for product reformulation, etc.), and limiting advertising and marketing for products of poor nutritional quality (especially among children),” she said.

SAN ANTONIO – In a large prospective, international cohort, food additive nitrates and nitrites, artificial sweeteners (especially aspartame and acesulfame-K), and dietary trans fatty acids were found to be associated with increased cancer risks.

The findings were reported in three poster presentations (P1-09-01, P1-09-02 and P3-12-35) at the 2021 San Antonio Breast Cancer Symposium from the ongoing French NutriNet-Santé web-based study of 171,000 people that was launched in France in 2009 to investigate nutrition and health relationships. The authors of the analyses note that while evidence of deleterious health effects has been established for the dietary focus of their studies, and cancer risks have been suspected, strong evidence of a cancer association has been lacking.

Nitrates and nitrites are used in processed meats to increase shelf life and to avoid bacterial growth, said Eloi Chazelas, PhD, Nutritional Epidemiology Research Team (EREN) at Sorbonne Paris Nord University. Dr. Chazelas looked at consumption of nitrites and nitrates through repeated 24 hour dietary records, linked to a comprehensive food composition database. The study’s main outcome measure was adjusted associations between nitrite and nitrate exposures and the risk of cancer (overall and by main cancer sites).

During follow-up, 966 breast and 400 prostate cancers were diagnosed among 3,311 first incident cancer cases. Breast cancer risk was elevated (HR = 1.24 [1.03-1.48], P = 0.02) among higher consumers of nitrates from food additives, especially with potassium nitrate consumption (HR = 1.25 [1.04-1.50], P = 0.01). Elevated prostate cancer risk was associated with nitrites (HR = 1.58 [1.14-2.18], P = 0.008), specifically for sodium nitrite (HR = 1.62 [1.17-2.25], P = 0.004). Nitrates and nitrites from natural sources were not associated significantly with higher cancer risk, Dr. Chazelas said.

He and his team found that food additive nitrates were positively associated with breast cancer risk, and food additive nitrites were positively associated with prostate cancer risk. “While these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of nitrite additives in the food industry,” said Dr. Chazelas, who is a doctoral candidate at Sorbonne Paris Nord University.

In “Breast and prostate cancer risk associated with nitrites and nitrates from food additives (P1-09-01),” the study included 102,046 adults from the French NutriNet-Santé prospective cohort (2009-2021). It examined associations between artificial sweetener intakes (total from all dietary sources, the most frequently consumed ones [aspartame e951, acesulfame-K e950 and sucralose e955]) and cancer risk (overall and by sites: breast, prostate and obesity-related cancers).

Overall cancer risk in people who consumed higher amounts of total sweeteners (i.e. above the median exposure in consumers) was elevated (n = 2,527 cases, hazard ratio = 1.12, 95 percent confidence interval = 1.00-1.25, P-trend=0.005), especially for aspartame (HR = 1.20 [1.05-1.38] P = 0.001) and acesulfame-K (HR = 1.18 [1.04-1.34] P = 0.003). Elevated breast cancer risks (among 723 cases) were observed for total sweeteners (HR = 1.25 [1.02-1.53] P = 0.01), for aspartame (HR = 1.33 [1.05-1.69] P = 0.007), and for acesulfame-K (HR = 1.39 [1.11-1.74] P = 0.003). Also, obesity-related cancers (1,509 cases) were increased for total sweeteners (HR = 1.16 [1.00-1.33] P = 0.02), for aspartame (HR = 1.22 [1.02-1.45] P = 0.01) and for acesulfame-K (HR = 1.23 [1.04-1.45] P = 0.01).

Artificial sweeteners are found in more than 10,000 foods and beverages, said Charlotte Debras, a doctoral candidate in nutritional epidemiology at Sorbonne Paris Nord University. “These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally,” she said.
 

Trans fatty acid intakes and cancer risk

Investigating associations between trans fatty acid intake (total ruminant [rTFAs], industrial [iTFAs], and corresponding specific isomers and cancer risk), the analysis of Gaëlle Wendeu-Foyet, PhD, Sorbonne Paris Nord University, found a total of 3,374 incident cancer cases (982 breast, 405 prostate) in an overall population of 104,909. Dietary intake of total TFAs was associated with higher prostate cancer risk (hazard ration for quartile 4 versus 1: 1.27, 1.11-1.77 P-trend = 0.005). Also, rTFAs were associated with increased overall cancer risk (1.16, 1.02-1.32 P-trend = 0.07), in particular the conjugated linoleic acid isomers (CLA) (1.19, 1.04-1.36 P-trend = 0.04). These associations were specifically observed for breast cancer (rTFAs: 1.35, 1.06-1.72 P-trend = 0.01; CLA: 1.29, 1.00-1.66 P-trend = 0.048), in particular before menopause (rTFAs: 1.68, 1.06-2.67 P-trend = 0.02; CLA: 2.013, 1.25-3.23 P-trend = 0.003). Several iTFAs were associated with overall (1.18, 1.06-1.31 P-trend = 0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30, 1.06-1.58 P-trend = 0.01; hexadecenoic acid: 1.28, 1.05-1.56 P-trend = 0.02) and prostate (transdocosenoic acid: 1.52, 1.09-2.12 P-trend = 0.07) cancer risks.

“These results support the WHO’s goal of achieving elimination from food supplies of industrially produced TFAs,” Dr. Foyet said. “The consumption of food products containing partially hydrogenated oils should be avoided.”

Nutrition, along with avoiding tobacco intake, is one of the main modifiable risk factors for chronic diseases. “There is a lot at stake in terms of prevention. This requires a combination of actions at the individual level to the public level by informing the public through food labeling,” Ms. Debras said.

It also requires influencing the context in which citizens evolve by encouraging manufacturers to improve their products (pricing policies, commitment charters for product reformulation, etc.), and limiting advertising and marketing for products of poor nutritional quality (especially among children),” she said.

SAN ANTONIO – Breast cancer survivors with chronic musculoskeletal pain may experience relief from pain with electroacupuncture and auricular acupuncture, according to a new study recently presented at the 2021 San Antonio Breast Cancer Symposium.

Both techniques led to clinically meaningful and persistent reduction of pain, but electroacupuncture was more effective in reducing pain severity, according to study author Wanqing Iris Zhi, MD, PhD, of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center in New York.

Among breast cancer survivors, Dr. Zhi said, chronic musculoskeletal pain is common and debilitating. In earlier results of the PEACE (Personalized Electroacupuncture versus Auricular Acupuncture Comparative Effectiveness) trial, both electroacupuncture and auricular acupuncture improved pain control better than usual care in cancer survivors. The comparative effectiveness between electroacupuncture and auricular acupuncture among breast cancer survivors, specifically for chronic musculoskeletal pain, remains unknown.

To evaluate potential differences between electroacupuncture and auricular acupuncture, Dr. Zhi et al. examined data from PEACE, a three-arm, parallel, single center randomized trial investigating electroacupuncture and auricular acupuncture for chronic musculoskeletal pain, compared with usual care. Among 360 cancer survivors in PEACE, mean age in 165 cancer survivors with a primary diagnosis of breast cancer was 60.3 years (35.8 percent non-White) with a mean of 5.4 years since their cancer diagnoses. Patients in both the electroacupuncture and auricular acupuncture groups received 10 weekly treatments. Change in mean Brief Pain Inventory (BPI) pain severity from baseline to week 12 was the primary endpoint, with BPI change to week 24 as a secondary endpoint. Usual care patients, after week 12, could receive 10 electroacupuncture treatments.

The most common locations of chronic musculoskeletal pain, Dr. Zhi observed, were lower back (24 percent), knee/leg (24 percent) and shoulder/elbow (14 percent). About 70 percent of patients were taking pain medication. Both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reductions among the evaluated breast cancer survivors. The change in BPI severity from baseline to week 12 was –0.29 (confidence interval, –0.08, 0.28) in the UC group. In the electroacupuncture group it was –2.65 (CI, –3.06, –2.25; P ≤0.001 from baseline) and –2.37 versus usual care (CI, –3.05, –1.68; P ≤0.001 versus UC). For the auricular acupuncture group, the change from baseline was –1.75 (CI, –2.15, –1.35; P ≤0.001 from baseline) and –1.46 versus usual care (CI, –2.14, –0.78; P ≤0.001 versus UC). The difference in BPI pain severity reduction from baseline between electroacupuncture and auricular acupuncture of –0.90 (CI, –1.45, –0.36) was statistically significant (P ≤0.001). Electroacupuncture also reduced pain severity significantly more than auricular acupuncture at week 24 (CI, –0.82, [–1.38, –0.27], P = 0.004).

Dr. Zhi concluded that among breast cancer survivors, although both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reduction, electroacupuncture was more effective at reducing pain severity.

She pointed out also that neither surgery type (mastectomy versus lumpectomy; P = 0.83) nor aromatase inhibitor versus tamoxifen versus neither (P = 0.59) was associated with BPI/severity response among electroacupuncture and auricular acupuncture patients.

“Both electroacupuncture and auricular acupuncture are significantly better than usual care, so it suggests that both acupuncture methods can be utilized for treating chronic muscle skeletal pain in breast cancer survivors, but electroacupuncture is preferred,” Dr. Zhi said.

“Auricular acupuncture can be more painful,” said PEACE principal investigator Jun Mao, MD, who is chair of integrative medicine at Memorial Sloan Kettering. “Ten percent of women could not tolerate the ear pain or discomfort. Electroacupuncture is generally well tolerated. People are more relaxed after treatment. If both are available, start with electroacupuncture,” he said.

SAN ANTONIO – Breast cancer survivors with chronic musculoskeletal pain may experience relief from pain with electroacupuncture and auricular acupuncture, according to a new study recently presented at the 2021 San Antonio Breast Cancer Symposium.

Both techniques led to clinically meaningful and persistent reduction of pain, but electroacupuncture was more effective in reducing pain severity, according to study author Wanqing Iris Zhi, MD, PhD, of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center in New York.

Among breast cancer survivors, Dr. Zhi said, chronic musculoskeletal pain is common and debilitating. In earlier results of the PEACE (Personalized Electroacupuncture versus Auricular Acupuncture Comparative Effectiveness) trial, both electroacupuncture and auricular acupuncture improved pain control better than usual care in cancer survivors. The comparative effectiveness between electroacupuncture and auricular acupuncture among breast cancer survivors, specifically for chronic musculoskeletal pain, remains unknown.

To evaluate potential differences between electroacupuncture and auricular acupuncture, Dr. Zhi et al. examined data from PEACE, a three-arm, parallel, single center randomized trial investigating electroacupuncture and auricular acupuncture for chronic musculoskeletal pain, compared with usual care. Among 360 cancer survivors in PEACE, mean age in 165 cancer survivors with a primary diagnosis of breast cancer was 60.3 years (35.8 percent non-White) with a mean of 5.4 years since their cancer diagnoses. Patients in both the electroacupuncture and auricular acupuncture groups received 10 weekly treatments. Change in mean Brief Pain Inventory (BPI) pain severity from baseline to week 12 was the primary endpoint, with BPI change to week 24 as a secondary endpoint. Usual care patients, after week 12, could receive 10 electroacupuncture treatments.

The most common locations of chronic musculoskeletal pain, Dr. Zhi observed, were lower back (24 percent), knee/leg (24 percent) and shoulder/elbow (14 percent). About 70 percent of patients were taking pain medication. Both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reductions among the evaluated breast cancer survivors. The change in BPI severity from baseline to week 12 was –0.29 (confidence interval, –0.08, 0.28) in the UC group. In the electroacupuncture group it was –2.65 (CI, –3.06, –2.25; P ≤0.001 from baseline) and –2.37 versus usual care (CI, –3.05, –1.68; P ≤0.001 versus UC). For the auricular acupuncture group, the change from baseline was –1.75 (CI, –2.15, –1.35; P ≤0.001 from baseline) and –1.46 versus usual care (CI, –2.14, –0.78; P ≤0.001 versus UC). The difference in BPI pain severity reduction from baseline between electroacupuncture and auricular acupuncture of –0.90 (CI, –1.45, –0.36) was statistically significant (P ≤0.001). Electroacupuncture also reduced pain severity significantly more than auricular acupuncture at week 24 (CI, –0.82, [–1.38, –0.27], P = 0.004).

Dr. Zhi concluded that among breast cancer survivors, although both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reduction, electroacupuncture was more effective at reducing pain severity.

She pointed out also that neither surgery type (mastectomy versus lumpectomy; P = 0.83) nor aromatase inhibitor versus tamoxifen versus neither (P = 0.59) was associated with BPI/severity response among electroacupuncture and auricular acupuncture patients.

“Both electroacupuncture and auricular acupuncture are significantly better than usual care, so it suggests that both acupuncture methods can be utilized for treating chronic muscle skeletal pain in breast cancer survivors, but electroacupuncture is preferred,” Dr. Zhi said.

“Auricular acupuncture can be more painful,” said PEACE principal investigator Jun Mao, MD, who is chair of integrative medicine at Memorial Sloan Kettering. “Ten percent of women could not tolerate the ear pain or discomfort. Electroacupuncture is generally well tolerated. People are more relaxed after treatment. If both are available, start with electroacupuncture,” he said.

SAN ANTONIO – Breast cancer survivors with chronic musculoskeletal pain may experience relief from pain with electroacupuncture and auricular acupuncture, according to a new study recently presented at the 2021 San Antonio Breast Cancer Symposium.

Both techniques led to clinically meaningful and persistent reduction of pain, but electroacupuncture was more effective in reducing pain severity, according to study author Wanqing Iris Zhi, MD, PhD, of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center in New York.

Among breast cancer survivors, Dr. Zhi said, chronic musculoskeletal pain is common and debilitating. In earlier results of the PEACE (Personalized Electroacupuncture versus Auricular Acupuncture Comparative Effectiveness) trial, both electroacupuncture and auricular acupuncture improved pain control better than usual care in cancer survivors. The comparative effectiveness between electroacupuncture and auricular acupuncture among breast cancer survivors, specifically for chronic musculoskeletal pain, remains unknown.

To evaluate potential differences between electroacupuncture and auricular acupuncture, Dr. Zhi et al. examined data from PEACE, a three-arm, parallel, single center randomized trial investigating electroacupuncture and auricular acupuncture for chronic musculoskeletal pain, compared with usual care. Among 360 cancer survivors in PEACE, mean age in 165 cancer survivors with a primary diagnosis of breast cancer was 60.3 years (35.8 percent non-White) with a mean of 5.4 years since their cancer diagnoses. Patients in both the electroacupuncture and auricular acupuncture groups received 10 weekly treatments. Change in mean Brief Pain Inventory (BPI) pain severity from baseline to week 12 was the primary endpoint, with BPI change to week 24 as a secondary endpoint. Usual care patients, after week 12, could receive 10 electroacupuncture treatments.

The most common locations of chronic musculoskeletal pain, Dr. Zhi observed, were lower back (24 percent), knee/leg (24 percent) and shoulder/elbow (14 percent). About 70 percent of patients were taking pain medication. Both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reductions among the evaluated breast cancer survivors. The change in BPI severity from baseline to week 12 was –0.29 (confidence interval, –0.08, 0.28) in the UC group. In the electroacupuncture group it was –2.65 (CI, –3.06, –2.25; P ≤0.001 from baseline) and –2.37 versus usual care (CI, –3.05, –1.68; P ≤0.001 versus UC). For the auricular acupuncture group, the change from baseline was –1.75 (CI, –2.15, –1.35; P ≤0.001 from baseline) and –1.46 versus usual care (CI, –2.14, –0.78; P ≤0.001 versus UC). The difference in BPI pain severity reduction from baseline between electroacupuncture and auricular acupuncture of –0.90 (CI, –1.45, –0.36) was statistically significant (P ≤0.001). Electroacupuncture also reduced pain severity significantly more than auricular acupuncture at week 24 (CI, –0.82, [–1.38, –0.27], P = 0.004).

Dr. Zhi concluded that among breast cancer survivors, although both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reduction, electroacupuncture was more effective at reducing pain severity.

She pointed out also that neither surgery type (mastectomy versus lumpectomy; P = 0.83) nor aromatase inhibitor versus tamoxifen versus neither (P = 0.59) was associated with BPI/severity response among electroacupuncture and auricular acupuncture patients.

“Both electroacupuncture and auricular acupuncture are significantly better than usual care, so it suggests that both acupuncture methods can be utilized for treating chronic muscle skeletal pain in breast cancer survivors, but electroacupuncture is preferred,” Dr. Zhi said.

“Auricular acupuncture can be more painful,” said PEACE principal investigator Jun Mao, MD, who is chair of integrative medicine at Memorial Sloan Kettering. “Ten percent of women could not tolerate the ear pain or discomfort. Electroacupuncture is generally well tolerated. People are more relaxed after treatment. If both are available, start with electroacupuncture,” he said.

On a recent Friday, oncologist Christine Berg, MD, devoted 3 hours to a webinar about electrification of heavy- and medium-duty trucks in Maryland.

It’s not the way most cancer specialists choose to spend their time. But Dr. Berg, who is board certified in medical oncology, radiation oncology, and internal medicine, has made air pollution her current focus. Through organizations such as the Public Employees for Environmental Responsibility, she is working to raise awareness of the huge impact it can have on cancer.

“I think oncologists can make a difference,” she said.

That’s why Dr. Berg took a keen interest in a recent study by ProPublica, the nonprofit journalism organization, that identified previously ignored “hot spots of cancer-causing air.” While the ProPublica report gives an incomplete picture of airborne carcinogens, it puts an important spotlight on industrial air pollution, Dr. Berg and other experts say.

Relying on data from the Environmental Protection Agency’s Risk-Screening Environmental Indicators (RSEI), ProPublica researchers estimated the effects of industrial air pollution around the country and found problems the EPA overlooked, they reported. “The EPA collects data on each individual facility, but it doesn’t consider the excess cancer risk from all of the facilities’ combined emissions,” reporter Lylla Younes and colleagues wrote. “ProPublica did.”

The ProPublica team produced a map of cancer-causing industrial air pollution hot spots. They estimated that 256,000 people in the United States live in areas where incidences of cancer caused by air pollution exceed the EPA’s upper limit of acceptable risk.

While some of the spots are scattered around the country, they are concentrated along the Gulf Coast of Texas and Louisiana. For example, near the Equistar Chemicals Bayport Chemical Plant in Pasadena, Texas, ProPublica calculated the increased risk of cancer at 1 in 220, “46 times the EPA’s acceptable risk.” (The agency defines an acceptable risk as less than a 1 in 10,000 chance of developing cancer.)

Almost all the hot spots with the highest level of risk are in southern United States “known for having weaker environmental regulations,” the report said.

The researchers also identified race as a risk factor. In predominantly Black census tracts, they estimated the risk from toxic air pollution is more than double the risk in predominantly White census tracts. It attributed this pattern to deliberate policies of redlining that segregated neighborhoods and to zoning ordinances that encouraged industry in communities of color.
 

Measuring risk not straightforward

In response to a query from this news organization, an EPA spokesperson provided a statement saying the RSEI data are not intended for the purpose used by ProPublica. “RSEI does not provide a risk assessment (e.g., excess cancer case estimates),” the statement said. The RSEI data are poorly suited to this purpose because they use “worst-case assumptions about toxicity and potential exposure where data are lacking, and also use simplifying assumptions to reduce the complexity of the calculations,” the statement said.

Instead, the data are meant as a kind of index to compare one place to another, or show changes over time, the agency said. In this way, it can prompt regulators to investigate further. “A more refined assessment is required before any conclusions about health impacts can be drawn.” The agency is working on just such a refined approach, per the EPA statement.

That’s not just bureaucratic stonewalling, said Stan Meiberg, PhD, MA, a former EPA official and director of graduate studies in sustainability at Wake Forest University in Winston-Salem, N.C. “To say that you can speak with great precision, that the risk of individuals getting cancer is 1 in 100, may be a little overstating the date on which that statement is based.”

Risk estimates are improving as citizens gain access to more sophisticated monitoring devices, he said. And the primary point of the ProPublica report, that the EPA has underestimated risk by looking at individual sources of pollution rather than combining them, is not an original one, Dr. Meiberg said. “This is an issue that’s been kicking around for quite some time.”

Still, it’s one that demands attention. EPA regulations have succeeded in reducing the overall risk from industrial air pollution over the past few decades. “But there remain areas of particular geographic concentrations,” he said. “And the ProPublica article hit two of them, which have been the subject of discussion for many years, the Houston Ship Channel area and the Baton Rouge to New Orleans industrial corridor where you have a significant proportion of all the chemical petrochemical industry in the United States.”

Improvements in containment of the pollutants, and changes to the industrial processes that produce them, can also help reduce exposure. These changes should occur in the context of dialogue within the communities exposed to the pollution, Dr. Meiberg said.
 

The role of cancer-causing airborne particulate matter

But even if measures are perfectly implemented, Joan Schiller, MD, will not breathe easy. An adjunct professor of oncology at the University of Virginia in Charlottesville, Dr. Schiller has researched the role of airborne particulate matter in causing cancer, a correlation barely mentioned in the ProPublica analysis, she pointed out.

Particulate matter contains a wide range of toxic substances, she said. Researchers have focused on particles 2.5 microns in diameter, or PM 2.5. Some studies have indicated that it’s responsible for one in seven deaths from lung cancer, Dr. Schiller said. “Air pollution also causes lung cancer in never smokers, people who’ve never smoked, not just in smokers.”

Power plants and automobile traffic may be more significant sources of PM 2.5 than industry, and wildfires have recently emerged as increasingly important source, a result of climate change and poor forest management, she said.

PM 2.5 doesn’t affect just lung cancer, said Alexandra White, PhD, an investigator at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. “My work, as well as work of others, is increasingly suggesting that air pollution is also related to breast cancer risk, in particular, air pollution that is arising from traffic related forces.” And more research is needed on other cancers, she said. “I think that the lack of findings of other cancer sites reflects a lack of study.”

Other pollutants not analyzed in the ProPublica report are also correlated to cancer risk. In a recent meta-analysis, researcher Stephan Gabet, PhD, PharmD, and colleagues at the University of Grenoble, France, estimated that 3.15% of new breast cancer cases in that country could be attributed to nitrogen dioxide and 2.15% to PM 10.

Sources of nitrogen dioxide, PM 2.5, and PM 10 in France include automobile traffic, inefficient wood-burning stoves, and coal-burning power plants in neighboring countries, Dr. Gabet said.

A good approach to reducing pollution from road traffic is the implementation of low-emission zones that prohibit the most polluting vehicles, he said. But a 2019 United Kingdom government study found that brake wear, tire wear, and road surface wear account for 72% of the PM 10 and 60% of the PM 2.5 pollution from road traffic, suggesting that a transition to electric vehicles won’t fix the problem. Better yet, is “the promotion of active modes like walking, cycling, etc., because like this, you can bring additional health gains due to the increase in physical activity,” he said.

Oncologists can help their patients reduce their exposure to air pollution, Dr. Schiller said. “If you have lung cancer, air pollution will hasten your demise. It makes you sicker. Oncologists should be telling their patients about this and advising them to move away from air pollution if possible, and also making sure they know to monitor the health of the air.”

On days when air pollution is high, patients may want to avoid exercising outdoors, or stay indoors altogether, Dr. Berg said. Air purifiers and N95 masks may also help.

And physicians can make a difference by speaking out in their communities, Dr. Schiller said. She is inviting oncologists to join a new group, Oncologists Understanding for Climate and Health. Through this group or on their own, oncologists can speak to their local legislatures or city councils in support of measures to reduce pollution, she said. “Doctors are trusted messengers.”

Dr. Berg disclosed affiliations with Grail, Mercy BioAnalytics and Lucid Diagnostics.

On a recent Friday, oncologist Christine Berg, MD, devoted 3 hours to a webinar about electrification of heavy- and medium-duty trucks in Maryland.

It’s not the way most cancer specialists choose to spend their time. But Dr. Berg, who is board certified in medical oncology, radiation oncology, and internal medicine, has made air pollution her current focus. Through organizations such as the Public Employees for Environmental Responsibility, she is working to raise awareness of the huge impact it can have on cancer.

“I think oncologists can make a difference,” she said.

That’s why Dr. Berg took a keen interest in a recent study by ProPublica, the nonprofit journalism organization, that identified previously ignored “hot spots of cancer-causing air.” While the ProPublica report gives an incomplete picture of airborne carcinogens, it puts an important spotlight on industrial air pollution, Dr. Berg and other experts say.

Relying on data from the Environmental Protection Agency’s Risk-Screening Environmental Indicators (RSEI), ProPublica researchers estimated the effects of industrial air pollution around the country and found problems the EPA overlooked, they reported. “The EPA collects data on each individual facility, but it doesn’t consider the excess cancer risk from all of the facilities’ combined emissions,” reporter Lylla Younes and colleagues wrote. “ProPublica did.”

The ProPublica team produced a map of cancer-causing industrial air pollution hot spots. They estimated that 256,000 people in the United States live in areas where incidences of cancer caused by air pollution exceed the EPA’s upper limit of acceptable risk.

While some of the spots are scattered around the country, they are concentrated along the Gulf Coast of Texas and Louisiana. For example, near the Equistar Chemicals Bayport Chemical Plant in Pasadena, Texas, ProPublica calculated the increased risk of cancer at 1 in 220, “46 times the EPA’s acceptable risk.” (The agency defines an acceptable risk as less than a 1 in 10,000 chance of developing cancer.)

Almost all the hot spots with the highest level of risk are in southern United States “known for having weaker environmental regulations,” the report said.

The researchers also identified race as a risk factor. In predominantly Black census tracts, they estimated the risk from toxic air pollution is more than double the risk in predominantly White census tracts. It attributed this pattern to deliberate policies of redlining that segregated neighborhoods and to zoning ordinances that encouraged industry in communities of color.
 

Measuring risk not straightforward

In response to a query from this news organization, an EPA spokesperson provided a statement saying the RSEI data are not intended for the purpose used by ProPublica. “RSEI does not provide a risk assessment (e.g., excess cancer case estimates),” the statement said. The RSEI data are poorly suited to this purpose because they use “worst-case assumptions about toxicity and potential exposure where data are lacking, and also use simplifying assumptions to reduce the complexity of the calculations,” the statement said.

Instead, the data are meant as a kind of index to compare one place to another, or show changes over time, the agency said. In this way, it can prompt regulators to investigate further. “A more refined assessment is required before any conclusions about health impacts can be drawn.” The agency is working on just such a refined approach, per the EPA statement.

That’s not just bureaucratic stonewalling, said Stan Meiberg, PhD, MA, a former EPA official and director of graduate studies in sustainability at Wake Forest University in Winston-Salem, N.C. “To say that you can speak with great precision, that the risk of individuals getting cancer is 1 in 100, may be a little overstating the date on which that statement is based.”

Risk estimates are improving as citizens gain access to more sophisticated monitoring devices, he said. And the primary point of the ProPublica report, that the EPA has underestimated risk by looking at individual sources of pollution rather than combining them, is not an original one, Dr. Meiberg said. “This is an issue that’s been kicking around for quite some time.”

Still, it’s one that demands attention. EPA regulations have succeeded in reducing the overall risk from industrial air pollution over the past few decades. “But there remain areas of particular geographic concentrations,” he said. “And the ProPublica article hit two of them, which have been the subject of discussion for many years, the Houston Ship Channel area and the Baton Rouge to New Orleans industrial corridor where you have a significant proportion of all the chemical petrochemical industry in the United States.”

Improvements in containment of the pollutants, and changes to the industrial processes that produce them, can also help reduce exposure. These changes should occur in the context of dialogue within the communities exposed to the pollution, Dr. Meiberg said.
 

The role of cancer-causing airborne particulate matter

But even if measures are perfectly implemented, Joan Schiller, MD, will not breathe easy. An adjunct professor of oncology at the University of Virginia in Charlottesville, Dr. Schiller has researched the role of airborne particulate matter in causing cancer, a correlation barely mentioned in the ProPublica analysis, she pointed out.

Particulate matter contains a wide range of toxic substances, she said. Researchers have focused on particles 2.5 microns in diameter, or PM 2.5. Some studies have indicated that it’s responsible for one in seven deaths from lung cancer, Dr. Schiller said. “Air pollution also causes lung cancer in never smokers, people who’ve never smoked, not just in smokers.”

Power plants and automobile traffic may be more significant sources of PM 2.5 than industry, and wildfires have recently emerged as increasingly important source, a result of climate change and poor forest management, she said.

PM 2.5 doesn’t affect just lung cancer, said Alexandra White, PhD, an investigator at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. “My work, as well as work of others, is increasingly suggesting that air pollution is also related to breast cancer risk, in particular, air pollution that is arising from traffic related forces.” And more research is needed on other cancers, she said. “I think that the lack of findings of other cancer sites reflects a lack of study.”

Other pollutants not analyzed in the ProPublica report are also correlated to cancer risk. In a recent meta-analysis, researcher Stephan Gabet, PhD, PharmD, and colleagues at the University of Grenoble, France, estimated that 3.15% of new breast cancer cases in that country could be attributed to nitrogen dioxide and 2.15% to PM 10.

Sources of nitrogen dioxide, PM 2.5, and PM 10 in France include automobile traffic, inefficient wood-burning stoves, and coal-burning power plants in neighboring countries, Dr. Gabet said.

A good approach to reducing pollution from road traffic is the implementation of low-emission zones that prohibit the most polluting vehicles, he said. But a 2019 United Kingdom government study found that brake wear, tire wear, and road surface wear account for 72% of the PM 10 and 60% of the PM 2.5 pollution from road traffic, suggesting that a transition to electric vehicles won’t fix the problem. Better yet, is “the promotion of active modes like walking, cycling, etc., because like this, you can bring additional health gains due to the increase in physical activity,” he said.

Oncologists can help their patients reduce their exposure to air pollution, Dr. Schiller said. “If you have lung cancer, air pollution will hasten your demise. It makes you sicker. Oncologists should be telling their patients about this and advising them to move away from air pollution if possible, and also making sure they know to monitor the health of the air.”

On days when air pollution is high, patients may want to avoid exercising outdoors, or stay indoors altogether, Dr. Berg said. Air purifiers and N95 masks may also help.

And physicians can make a difference by speaking out in their communities, Dr. Schiller said. She is inviting oncologists to join a new group, Oncologists Understanding for Climate and Health. Through this group or on their own, oncologists can speak to their local legislatures or city councils in support of measures to reduce pollution, she said. “Doctors are trusted messengers.”

Dr. Berg disclosed affiliations with Grail, Mercy BioAnalytics and Lucid Diagnostics.

On a recent Friday, oncologist Christine Berg, MD, devoted 3 hours to a webinar about electrification of heavy- and medium-duty trucks in Maryland.

It’s not the way most cancer specialists choose to spend their time. But Dr. Berg, who is board certified in medical oncology, radiation oncology, and internal medicine, has made air pollution her current focus. Through organizations such as the Public Employees for Environmental Responsibility, she is working to raise awareness of the huge impact it can have on cancer.

“I think oncologists can make a difference,” she said.

That’s why Dr. Berg took a keen interest in a recent study by ProPublica, the nonprofit journalism organization, that identified previously ignored “hot spots of cancer-causing air.” While the ProPublica report gives an incomplete picture of airborne carcinogens, it puts an important spotlight on industrial air pollution, Dr. Berg and other experts say.

Relying on data from the Environmental Protection Agency’s Risk-Screening Environmental Indicators (RSEI), ProPublica researchers estimated the effects of industrial air pollution around the country and found problems the EPA overlooked, they reported. “The EPA collects data on each individual facility, but it doesn’t consider the excess cancer risk from all of the facilities’ combined emissions,” reporter Lylla Younes and colleagues wrote. “ProPublica did.”

The ProPublica team produced a map of cancer-causing industrial air pollution hot spots. They estimated that 256,000 people in the United States live in areas where incidences of cancer caused by air pollution exceed the EPA’s upper limit of acceptable risk.

While some of the spots are scattered around the country, they are concentrated along the Gulf Coast of Texas and Louisiana. For example, near the Equistar Chemicals Bayport Chemical Plant in Pasadena, Texas, ProPublica calculated the increased risk of cancer at 1 in 220, “46 times the EPA’s acceptable risk.” (The agency defines an acceptable risk as less than a 1 in 10,000 chance of developing cancer.)

Almost all the hot spots with the highest level of risk are in southern United States “known for having weaker environmental regulations,” the report said.

The researchers also identified race as a risk factor. In predominantly Black census tracts, they estimated the risk from toxic air pollution is more than double the risk in predominantly White census tracts. It attributed this pattern to deliberate policies of redlining that segregated neighborhoods and to zoning ordinances that encouraged industry in communities of color.
 

Measuring risk not straightforward

In response to a query from this news organization, an EPA spokesperson provided a statement saying the RSEI data are not intended for the purpose used by ProPublica. “RSEI does not provide a risk assessment (e.g., excess cancer case estimates),” the statement said. The RSEI data are poorly suited to this purpose because they use “worst-case assumptions about toxicity and potential exposure where data are lacking, and also use simplifying assumptions to reduce the complexity of the calculations,” the statement said.

Instead, the data are meant as a kind of index to compare one place to another, or show changes over time, the agency said. In this way, it can prompt regulators to investigate further. “A more refined assessment is required before any conclusions about health impacts can be drawn.” The agency is working on just such a refined approach, per the EPA statement.

That’s not just bureaucratic stonewalling, said Stan Meiberg, PhD, MA, a former EPA official and director of graduate studies in sustainability at Wake Forest University in Winston-Salem, N.C. “To say that you can speak with great precision, that the risk of individuals getting cancer is 1 in 100, may be a little overstating the date on which that statement is based.”

Risk estimates are improving as citizens gain access to more sophisticated monitoring devices, he said. And the primary point of the ProPublica report, that the EPA has underestimated risk by looking at individual sources of pollution rather than combining them, is not an original one, Dr. Meiberg said. “This is an issue that’s been kicking around for quite some time.”

Still, it’s one that demands attention. EPA regulations have succeeded in reducing the overall risk from industrial air pollution over the past few decades. “But there remain areas of particular geographic concentrations,” he said. “And the ProPublica article hit two of them, which have been the subject of discussion for many years, the Houston Ship Channel area and the Baton Rouge to New Orleans industrial corridor where you have a significant proportion of all the chemical petrochemical industry in the United States.”

Improvements in containment of the pollutants, and changes to the industrial processes that produce them, can also help reduce exposure. These changes should occur in the context of dialogue within the communities exposed to the pollution, Dr. Meiberg said.
 

The role of cancer-causing airborne particulate matter

But even if measures are perfectly implemented, Joan Schiller, MD, will not breathe easy. An adjunct professor of oncology at the University of Virginia in Charlottesville, Dr. Schiller has researched the role of airborne particulate matter in causing cancer, a correlation barely mentioned in the ProPublica analysis, she pointed out.

Particulate matter contains a wide range of toxic substances, she said. Researchers have focused on particles 2.5 microns in diameter, or PM 2.5. Some studies have indicated that it’s responsible for one in seven deaths from lung cancer, Dr. Schiller said. “Air pollution also causes lung cancer in never smokers, people who’ve never smoked, not just in smokers.”

Power plants and automobile traffic may be more significant sources of PM 2.5 than industry, and wildfires have recently emerged as increasingly important source, a result of climate change and poor forest management, she said.

PM 2.5 doesn’t affect just lung cancer, said Alexandra White, PhD, an investigator at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. “My work, as well as work of others, is increasingly suggesting that air pollution is also related to breast cancer risk, in particular, air pollution that is arising from traffic related forces.” And more research is needed on other cancers, she said. “I think that the lack of findings of other cancer sites reflects a lack of study.”

Other pollutants not analyzed in the ProPublica report are also correlated to cancer risk. In a recent meta-analysis, researcher Stephan Gabet, PhD, PharmD, and colleagues at the University of Grenoble, France, estimated that 3.15% of new breast cancer cases in that country could be attributed to nitrogen dioxide and 2.15% to PM 10.

Sources of nitrogen dioxide, PM 2.5, and PM 10 in France include automobile traffic, inefficient wood-burning stoves, and coal-burning power plants in neighboring countries, Dr. Gabet said.

A good approach to reducing pollution from road traffic is the implementation of low-emission zones that prohibit the most polluting vehicles, he said. But a 2019 United Kingdom government study found that brake wear, tire wear, and road surface wear account for 72% of the PM 10 and 60% of the PM 2.5 pollution from road traffic, suggesting that a transition to electric vehicles won’t fix the problem. Better yet, is “the promotion of active modes like walking, cycling, etc., because like this, you can bring additional health gains due to the increase in physical activity,” he said.

Oncologists can help their patients reduce their exposure to air pollution, Dr. Schiller said. “If you have lung cancer, air pollution will hasten your demise. It makes you sicker. Oncologists should be telling their patients about this and advising them to move away from air pollution if possible, and also making sure they know to monitor the health of the air.”

On days when air pollution is high, patients may want to avoid exercising outdoors, or stay indoors altogether, Dr. Berg said. Air purifiers and N95 masks may also help.

And physicians can make a difference by speaking out in their communities, Dr. Schiller said. She is inviting oncologists to join a new group, Oncologists Understanding for Climate and Health. Through this group or on their own, oncologists can speak to their local legislatures or city councils in support of measures to reduce pollution, she said. “Doctors are trusted messengers.”

Dr. Berg disclosed affiliations with Grail, Mercy BioAnalytics and Lucid Diagnostics.

Identification of pulmonary nodules in older adults who smoke immediately brings concern for malignancy in the mind of clinicians. This is particularly the case in patients with significant smoking history. According to the National Cancer Institute in 2019, 12.9% of all new cancer cases were lung cancers.¹ Screening for lung cancer, especially in patients with increased risk from smoking, is imperative to early detection and treatment. However, 20% of patients will be overdiagnosed by lung cancer-screening techniques.² The rate of malignancy noted on a patient’s first screening computed tomography (CT) scan was between 3.7% and 5.5%.³

Rheumatoid arthritis (RA) is an autoimmune inflammatory condition that mainly affects the joints. Extraarticular manifestations can arise in various locations throughout the body, however. These manifestations are commonly observed in the skin, heart, and lungs.⁴ Prevalence of pulmonary rheumatoid nodules ranges from < 0.4% in radiologic studies to 32% in lung biopsies of patients with RA and nodules.⁵

Furthermore, there is a strong association between the risk of rheumatoid nodules in patients with positive serum rheumatoid factor (RF) and smoking history.⁶ Solitary pulmonary nodules in patients with RA can coexist with bronchogenic carcinoma, making their diagnosis more important.⁷

Case Presentation

A 54-year-old woman with a 30 pack-year smoking history and history of RA initially presented to the emergency department for cough and dyspnea for 5-day duration. Her initial diagnosis was bronchitis based on presenting symptom profile. A chest CT demonstrated 3 cavitary pulmonary nodules, 1 measuring 2.4 x 2.0 cm in the right middle lobe, and 2 additional nodules, measuring 1.8 x 1.4 and 1.5 x 1.4 in the left upper lobe (Figure). She had no improvement of symptoms after a 7-day course of doxycycline. The patient was taking methotrexate 15 mg weekly and golimumab 50 mg subcutaneously every 4 weeks as treatment for RA, prescribed by her rheumatologist.

Pulmonology was consulted and a positron emission tomography-CT (PET-CT) confirmed several cavitary pulmonary nodules involving both lungs with no suspicious fluorodeoxyglucose (FDG) uptake. The largest lesion was in the right middle lobe with FDG uptake of 1.9. Additional nodules were found in the left upper lobe, measuring 1.8 x 1.4 cm with FDG of 4.01, and in the left lung apex, measuring 1.5 x 1.4 cm with uptake of 3.53. CTguided percutaneous fine needle aspiration (PFNA) of the right middle lobe lung nodule demonstrated granuloma with central inflammatory debris. Grocott methenamine silver (GMS) stain was negative for fungal organism, acid-fast bacteria (AFB) stain was negative for acid-fast bacilli, and CD20 and CD3 immunostaining demonstrated mixed B- and T-cell populations. There was no evidence of atypia or malignancy. The biopsy demonstrated granuloma with central inflammatory debris on a background of densely fibrotic tissue and lympho-plasmatic inflammation. This finding confirmed the diagnosis of RA with pulmonary involvement.

Outpatient follow-up was established with a pulmonologist and rheumatologist. Methotrexate 15 mg weekly and golimumab subcutaneously 50 mg every 4 weeks were prescribed for the patient. The nodules are being monitored based on Fleischer guidelines with CT imaging 3 to 6 months following initial presentation. Further imaging will be considered at 18 to 24 months as well to further assess stability of the nodules and monitor for changes in size, shape, and necrosis. The patient also was encouraged to quit smoking. Her clinical course since the diagnosis has been stable.

Discussion

The differential diagnosis for new multiple pulmonary nodules on imaging studies is broad and includes infectious processes, such as tuberculosis, as well as other mycobacterial, fungal, and bacterial infections. Noninfectious causes of lung disease are an even broader category of consideration. Noninfectious pulmonary nodules differential includes sarcoidosis, granulomatous with polyangiitis, hypersensitivity pneumonitis, methotrexate drug reaction, pulmonary manifestations of systemic conditions, such as RA chronic granulomatous disease and malignancy.⁸ Bronchogenic carcinoma was suspected in this patient due to her smoking history. Squamous cell carcinoma was also considered as the lesion was cavitary. AFB and GMS stains were negative for fungi. Langerhans cell histiocytosis were considered but ruled out as these lesions contain larger numbers of eosinophils than described in the pathology report. Histoplasma and coccidiosis laboratory tests were obtained as the patient lived in a region endemic to both these fungi but were negative (Table). A diagnosis of rheumatoid nodule was made based on the clinical setting, typical radiographic, histopathology features, and negative cultures.

This case is unique due to the quality and location of the rheumatoid nodules within the lungs. Pulmonary manifestations of RA are usually subcutaneous or subpleural, solid, and peripherally located^.9 This patient’s nodules were necrobiotic and located within the lung parenchyma. There was significant cavitation. These factors are atypical features of pulmonary RA.

Pulmonary RA can have many associated symptoms and remains an important factor in patient mortality. Estimates demonstrate that 10 to 20% of RA-related deaths are secondary to pulmonary manifestations.¹⁰ There are a wide array of symptoms and presentations to be aware of clinically. These symptoms are often nondescript, widely sensitive to many disease processes, and nonspecific to pulmonary RA. These symptoms include dyspnea, wheezing, and nonproductive cough.¹⁰ Bronchiectasis is a common symptom as well as small airway obstruction.¹⁰ Consolidated necrobiotic lesions are present in up to 20% of pulmonary RA cases.¹⁰ Generally these lesions are asymptomatic but can also be associated with pneumothorax, hemoptysis, and airway obstruction.10 Awareness of these symptoms is important for diagnosis and monitoring clinical improvement in patients.

Further workup is necessary to differentiate malignancy-related pulmonary nodules and other causes; if the index of suspicion is high for malignancy as in our case, the workup should be more aggressive. Biopsy is mandatory in such cases to rule out infections and malignancy, as it is highly sensitive and specific. The main problem hindering management is when a clinician fails to include this in their differential diagnosis. This further elucidates the importance of awareness of this diagnosis. Suspicious lesions in a proper clinical setting should be followed up by imaging studies and confirmatory histopathological diagnosis. Typical follow-up is 3 months after initial presentation to assess stability and possibly 18 to 24 months as well based on Fleischer guidelines.

Various treatment modalities have been tried as per literature, including tocilizumab and rituximab. ^11,12 Our patient is currently being treated with golimumab based on outpatient rheumatologist recommendations.

Conclusions

This case demonstrates the importance of a careful workup to narrow a broad differential. Medical diagnosis of pulmonary nodules requires an in-depth workup, including clinical evaluation, laboratory and pulmonary functions tests, as well as various imaging studies.

Identification of pulmonary nodules in older adults who smoke immediately brings concern for malignancy in the mind of clinicians. This is particularly the case in patients with significant smoking history. According to the National Cancer Institute in 2019, 12.9% of all new cancer cases were lung cancers.¹ Screening for lung cancer, especially in patients with increased risk from smoking, is imperative to early detection and treatment. However, 20% of patients will be overdiagnosed by lung cancer-screening techniques.² The rate of malignancy noted on a patient’s first screening computed tomography (CT) scan was between 3.7% and 5.5%.³

Rheumatoid arthritis (RA) is an autoimmune inflammatory condition that mainly affects the joints. Extraarticular manifestations can arise in various locations throughout the body, however. These manifestations are commonly observed in the skin, heart, and lungs.⁴ Prevalence of pulmonary rheumatoid nodules ranges from < 0.4% in radiologic studies to 32% in lung biopsies of patients with RA and nodules.⁵

Furthermore, there is a strong association between the risk of rheumatoid nodules in patients with positive serum rheumatoid factor (RF) and smoking history.⁶ Solitary pulmonary nodules in patients with RA can coexist with bronchogenic carcinoma, making their diagnosis more important.⁷

Case Presentation

A 54-year-old woman with a 30 pack-year smoking history and history of RA initially presented to the emergency department for cough and dyspnea for 5-day duration. Her initial diagnosis was bronchitis based on presenting symptom profile. A chest CT demonstrated 3 cavitary pulmonary nodules, 1 measuring 2.4 x 2.0 cm in the right middle lobe, and 2 additional nodules, measuring 1.8 x 1.4 and 1.5 x 1.4 in the left upper lobe (Figure). She had no improvement of symptoms after a 7-day course of doxycycline. The patient was taking methotrexate 15 mg weekly and golimumab 50 mg subcutaneously every 4 weeks as treatment for RA, prescribed by her rheumatologist.

Pulmonology was consulted and a positron emission tomography-CT (PET-CT) confirmed several cavitary pulmonary nodules involving both lungs with no suspicious fluorodeoxyglucose (FDG) uptake. The largest lesion was in the right middle lobe with FDG uptake of 1.9. Additional nodules were found in the left upper lobe, measuring 1.8 x 1.4 cm with FDG of 4.01, and in the left lung apex, measuring 1.5 x 1.4 cm with uptake of 3.53. CTguided percutaneous fine needle aspiration (PFNA) of the right middle lobe lung nodule demonstrated granuloma with central inflammatory debris. Grocott methenamine silver (GMS) stain was negative for fungal organism, acid-fast bacteria (AFB) stain was negative for acid-fast bacilli, and CD20 and CD3 immunostaining demonstrated mixed B- and T-cell populations. There was no evidence of atypia or malignancy. The biopsy demonstrated granuloma with central inflammatory debris on a background of densely fibrotic tissue and lympho-plasmatic inflammation. This finding confirmed the diagnosis of RA with pulmonary involvement.

Outpatient follow-up was established with a pulmonologist and rheumatologist. Methotrexate 15 mg weekly and golimumab subcutaneously 50 mg every 4 weeks were prescribed for the patient. The nodules are being monitored based on Fleischer guidelines with CT imaging 3 to 6 months following initial presentation. Further imaging will be considered at 18 to 24 months as well to further assess stability of the nodules and monitor for changes in size, shape, and necrosis. The patient also was encouraged to quit smoking. Her clinical course since the diagnosis has been stable.

Discussion

The differential diagnosis for new multiple pulmonary nodules on imaging studies is broad and includes infectious processes, such as tuberculosis, as well as other mycobacterial, fungal, and bacterial infections. Noninfectious causes of lung disease are an even broader category of consideration. Noninfectious pulmonary nodules differential includes sarcoidosis, granulomatous with polyangiitis, hypersensitivity pneumonitis, methotrexate drug reaction, pulmonary manifestations of systemic conditions, such as RA chronic granulomatous disease and malignancy.⁸ Bronchogenic carcinoma was suspected in this patient due to her smoking history. Squamous cell carcinoma was also considered as the lesion was cavitary. AFB and GMS stains were negative for fungi. Langerhans cell histiocytosis were considered but ruled out as these lesions contain larger numbers of eosinophils than described in the pathology report. Histoplasma and coccidiosis laboratory tests were obtained as the patient lived in a region endemic to both these fungi but were negative (Table). A diagnosis of rheumatoid nodule was made based on the clinical setting, typical radiographic, histopathology features, and negative cultures.

This case is unique due to the quality and location of the rheumatoid nodules within the lungs. Pulmonary manifestations of RA are usually subcutaneous or subpleural, solid, and peripherally located^.9 This patient’s nodules were necrobiotic and located within the lung parenchyma. There was significant cavitation. These factors are atypical features of pulmonary RA.

Pulmonary RA can have many associated symptoms and remains an important factor in patient mortality. Estimates demonstrate that 10 to 20% of RA-related deaths are secondary to pulmonary manifestations.¹⁰ There are a wide array of symptoms and presentations to be aware of clinically. These symptoms are often nondescript, widely sensitive to many disease processes, and nonspecific to pulmonary RA. These symptoms include dyspnea, wheezing, and nonproductive cough.¹⁰ Bronchiectasis is a common symptom as well as small airway obstruction.¹⁰ Consolidated necrobiotic lesions are present in up to 20% of pulmonary RA cases.¹⁰ Generally these lesions are asymptomatic but can also be associated with pneumothorax, hemoptysis, and airway obstruction.10 Awareness of these symptoms is important for diagnosis and monitoring clinical improvement in patients.

Further workup is necessary to differentiate malignancy-related pulmonary nodules and other causes; if the index of suspicion is high for malignancy as in our case, the workup should be more aggressive. Biopsy is mandatory in such cases to rule out infections and malignancy, as it is highly sensitive and specific. The main problem hindering management is when a clinician fails to include this in their differential diagnosis. This further elucidates the importance of awareness of this diagnosis. Suspicious lesions in a proper clinical setting should be followed up by imaging studies and confirmatory histopathological diagnosis. Typical follow-up is 3 months after initial presentation to assess stability and possibly 18 to 24 months as well based on Fleischer guidelines.

Various treatment modalities have been tried as per literature, including tocilizumab and rituximab. ^11,12 Our patient is currently being treated with golimumab based on outpatient rheumatologist recommendations.

Conclusions

This case demonstrates the importance of a careful workup to narrow a broad differential. Medical diagnosis of pulmonary nodules requires an in-depth workup, including clinical evaluation, laboratory and pulmonary functions tests, as well as various imaging studies.

Identification of pulmonary nodules in older adults who smoke immediately brings concern for malignancy in the mind of clinicians. This is particularly the case in patients with significant smoking history. According to the National Cancer Institute in 2019, 12.9% of all new cancer cases were lung cancers.¹ Screening for lung cancer, especially in patients with increased risk from smoking, is imperative to early detection and treatment. However, 20% of patients will be overdiagnosed by lung cancer-screening techniques.² The rate of malignancy noted on a patient’s first screening computed tomography (CT) scan was between 3.7% and 5.5%.³

Rheumatoid arthritis (RA) is an autoimmune inflammatory condition that mainly affects the joints. Extraarticular manifestations can arise in various locations throughout the body, however. These manifestations are commonly observed in the skin, heart, and lungs.⁴ Prevalence of pulmonary rheumatoid nodules ranges from < 0.4% in radiologic studies to 32% in lung biopsies of patients with RA and nodules.⁵

Furthermore, there is a strong association between the risk of rheumatoid nodules in patients with positive serum rheumatoid factor (RF) and smoking history.⁶ Solitary pulmonary nodules in patients with RA can coexist with bronchogenic carcinoma, making their diagnosis more important.⁷

Case Presentation

A 54-year-old woman with a 30 pack-year smoking history and history of RA initially presented to the emergency department for cough and dyspnea for 5-day duration. Her initial diagnosis was bronchitis based on presenting symptom profile. A chest CT demonstrated 3 cavitary pulmonary nodules, 1 measuring 2.4 x 2.0 cm in the right middle lobe, and 2 additional nodules, measuring 1.8 x 1.4 and 1.5 x 1.4 in the left upper lobe (Figure). She had no improvement of symptoms after a 7-day course of doxycycline. The patient was taking methotrexate 15 mg weekly and golimumab 50 mg subcutaneously every 4 weeks as treatment for RA, prescribed by her rheumatologist.

Pulmonology was consulted and a positron emission tomography-CT (PET-CT) confirmed several cavitary pulmonary nodules involving both lungs with no suspicious fluorodeoxyglucose (FDG) uptake. The largest lesion was in the right middle lobe with FDG uptake of 1.9. Additional nodules were found in the left upper lobe, measuring 1.8 x 1.4 cm with FDG of 4.01, and in the left lung apex, measuring 1.5 x 1.4 cm with uptake of 3.53. CTguided percutaneous fine needle aspiration (PFNA) of the right middle lobe lung nodule demonstrated granuloma with central inflammatory debris. Grocott methenamine silver (GMS) stain was negative for fungal organism, acid-fast bacteria (AFB) stain was negative for acid-fast bacilli, and CD20 and CD3 immunostaining demonstrated mixed B- and T-cell populations. There was no evidence of atypia or malignancy. The biopsy demonstrated granuloma with central inflammatory debris on a background of densely fibrotic tissue and lympho-plasmatic inflammation. This finding confirmed the diagnosis of RA with pulmonary involvement.

Outpatient follow-up was established with a pulmonologist and rheumatologist. Methotrexate 15 mg weekly and golimumab subcutaneously 50 mg every 4 weeks were prescribed for the patient. The nodules are being monitored based on Fleischer guidelines with CT imaging 3 to 6 months following initial presentation. Further imaging will be considered at 18 to 24 months as well to further assess stability of the nodules and monitor for changes in size, shape, and necrosis. The patient also was encouraged to quit smoking. Her clinical course since the diagnosis has been stable.

Discussion

The differential diagnosis for new multiple pulmonary nodules on imaging studies is broad and includes infectious processes, such as tuberculosis, as well as other mycobacterial, fungal, and bacterial infections. Noninfectious causes of lung disease are an even broader category of consideration. Noninfectious pulmonary nodules differential includes sarcoidosis, granulomatous with polyangiitis, hypersensitivity pneumonitis, methotrexate drug reaction, pulmonary manifestations of systemic conditions, such as RA chronic granulomatous disease and malignancy.⁸ Bronchogenic carcinoma was suspected in this patient due to her smoking history. Squamous cell carcinoma was also considered as the lesion was cavitary. AFB and GMS stains were negative for fungi. Langerhans cell histiocytosis were considered but ruled out as these lesions contain larger numbers of eosinophils than described in the pathology report. Histoplasma and coccidiosis laboratory tests were obtained as the patient lived in a region endemic to both these fungi but were negative (Table). A diagnosis of rheumatoid nodule was made based on the clinical setting, typical radiographic, histopathology features, and negative cultures.

This case is unique due to the quality and location of the rheumatoid nodules within the lungs. Pulmonary manifestations of RA are usually subcutaneous or subpleural, solid, and peripherally located^.9 This patient’s nodules were necrobiotic and located within the lung parenchyma. There was significant cavitation. These factors are atypical features of pulmonary RA.

Pulmonary RA can have many associated symptoms and remains an important factor in patient mortality. Estimates demonstrate that 10 to 20% of RA-related deaths are secondary to pulmonary manifestations.¹⁰ There are a wide array of symptoms and presentations to be aware of clinically. These symptoms are often nondescript, widely sensitive to many disease processes, and nonspecific to pulmonary RA. These symptoms include dyspnea, wheezing, and nonproductive cough.¹⁰ Bronchiectasis is a common symptom as well as small airway obstruction.¹⁰ Consolidated necrobiotic lesions are present in up to 20% of pulmonary RA cases.¹⁰ Generally these lesions are asymptomatic but can also be associated with pneumothorax, hemoptysis, and airway obstruction.10 Awareness of these symptoms is important for diagnosis and monitoring clinical improvement in patients.

Further workup is necessary to differentiate malignancy-related pulmonary nodules and other causes; if the index of suspicion is high for malignancy as in our case, the workup should be more aggressive. Biopsy is mandatory in such cases to rule out infections and malignancy, as it is highly sensitive and specific. The main problem hindering management is when a clinician fails to include this in their differential diagnosis. This further elucidates the importance of awareness of this diagnosis. Suspicious lesions in a proper clinical setting should be followed up by imaging studies and confirmatory histopathological diagnosis. Typical follow-up is 3 months after initial presentation to assess stability and possibly 18 to 24 months as well based on Fleischer guidelines.

Various treatment modalities have been tried as per literature, including tocilizumab and rituximab. ^11,12 Our patient is currently being treated with golimumab based on outpatient rheumatologist recommendations.

Conclusions

This case demonstrates the importance of a careful workup to narrow a broad differential. Medical diagnosis of pulmonary nodules requires an in-depth workup, including clinical evaluation, laboratory and pulmonary functions tests, as well as various imaging studies.

New research provides more evidence that antipsychotics that raise prolactin levels are tied to a significantly increased risk for breast cancer.

The relative risk for breast cancer was 62% higher in women who took category 1 antipsychotic medications associated with high prolactin levels. These include haloperidol (Haldol), paliperidone (Invega), and risperidone (Risperdal). Additionally, the risk was 54% higher in those taking category 2 antipsychotics that have mid-range effects on prolactin. These include iloperidone (Fanapt), lurasidone (Latuda), and olanzapine (Zyprexa).

In contrast, category 3 antipsychotics which have a lesser effect on prolactin levels were not associated with any increase in breast cancer risk. These drugs include aripiprazole (Abilify), asenapine (Saphris), brexpiprazole (Rexulti), cariprazine (Vraylar), clozapine (multiple brands), quetiapine (Seroquel), and ziprasidone (Geodon).

While the “absolute” breast cancer risk for these drugs is unclear, “we can make the case that high circulating prolactin levels are associated with breast cancer risk. This follows what is already known about prolactin from prior studies, notably the nurses’ health studies,” Tahir Rahman, MD, associate professor of psychiatry, Washington University School of Medicine, St. Louis, told this news organization.

“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr. Rahman added in a news release.

The study was published online Dec. 3 in the Journal of Clinical Psychopharmacology.
 

Test prolactin levels

Using administrative claims data, the researchers evaluated breast cancer risk in women aged 18-64 exposed to antipsychotic medications compared with anticonvulsants and/or lithium. 

They identified 914 cases of invasive breast cancer among 540,737 women.

Roughly 52% of the study population filled at least one prescription for a category 3 antipsychotic agent, whereas 15% filled at least one prescription for a category 1 agent; 49% of women filled at least one prescription for an anticonvulsant medication during the study period.

Exposure to all antipsychotics was independently associated with a 35% increased risk for breast cancer (adjusted hazard ratio, 1.35; 95% CI, 1.14-1.61), the study team found.

Compared with anticonvulsants or lithium, the risk for breast cancer was significantly increased for high prolactin (category 1) antipsychotics (adjusted hazard ratio, 1.62; 95% CI, 1.30-2.03) and for mid-prolactin (category 2) drugs (aHR 1.54; 95% CI, 1.19-1.99), with no increased risk for category 3 antipsychotics.

“Our research is obviously of interest for preventing breast cancer in antipsychotic-treated patients. Checking a blood prolactin level is cheap and easy [and a high level is] fairly simple to mitigate,” said Dr. Rahman.
 

A matter of debate

Reached for comment, Christoph Correll, MD, professor of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said, “The potential elevation of breast cancer risk depending on the dose and time of treatment with antipsychotic medications with varying degrees of prolactin-raising properties has been a topic of research and matter of debate.”

This new study “adds another data point indicating that antipsychotics that are associated on average with a higher prolactin-raising effect than other antipsychotics may increase the risk of breast cancer in women to some degree,” said Dr. Correll, who was not involved with the study.

However, he cautioned that “naturalistic data are always vulnerable to residual confounding, for example, unmeasured effects that could also at least partially explain the results, and the follow-up time of only 4 years (maximum 6 years) in this study was relatively short.

“Nevertheless, given availability of many different antipsychotics with varying degrees of prolactin-raising potential, in women requiring antipsychotic treatment, less prolactin-raising antipsychotics may be preferable,” Dr. Correll said.

“In women receiving prolactin-raising antipsychotics for medium- and longer-term maintenance therapy, prolactin levels should be monitored,” he added.

When an elevated prolactin level is detected, this should be addressed “either via dose reduction, a switch to an alternative antipsychotic that does not raise prolactin levels significantly, or the addition of a partial or full D2 agonist when the prolactin-raising antipsychotic should be continued based on individualized risk assessment,” Dr. Correll advised.

This work was supported by an award from the Alvin J. Siteman Cancer Center; the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health; the Taylor Family Institute for Innovative Psychiatric Research; and the Center for Brain Research in Mood Disorders. The authors have disclosed no relevant financial relationships. Dr. Correll has received royalties from UpToDate and is a stock option holder of LB Pharma.

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

New research provides more evidence that antipsychotics that raise prolactin levels are tied to a significantly increased risk for breast cancer.

The relative risk for breast cancer was 62% higher in women who took category 1 antipsychotic medications associated with high prolactin levels. These include haloperidol (Haldol), paliperidone (Invega), and risperidone (Risperdal). Additionally, the risk was 54% higher in those taking category 2 antipsychotics that have mid-range effects on prolactin. These include iloperidone (Fanapt), lurasidone (Latuda), and olanzapine (Zyprexa).

In contrast, category 3 antipsychotics which have a lesser effect on prolactin levels were not associated with any increase in breast cancer risk. These drugs include aripiprazole (Abilify), asenapine (Saphris), brexpiprazole (Rexulti), cariprazine (Vraylar), clozapine (multiple brands), quetiapine (Seroquel), and ziprasidone (Geodon).

While the “absolute” breast cancer risk for these drugs is unclear, “we can make the case that high circulating prolactin levels are associated with breast cancer risk. This follows what is already known about prolactin from prior studies, notably the nurses’ health studies,” Tahir Rahman, MD, associate professor of psychiatry, Washington University School of Medicine, St. Louis, told this news organization.

“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr. Rahman added in a news release.

The study was published online Dec. 3 in the Journal of Clinical Psychopharmacology.
 

Test prolactin levels

Using administrative claims data, the researchers evaluated breast cancer risk in women aged 18-64 exposed to antipsychotic medications compared with anticonvulsants and/or lithium. 

They identified 914 cases of invasive breast cancer among 540,737 women.

Roughly 52% of the study population filled at least one prescription for a category 3 antipsychotic agent, whereas 15% filled at least one prescription for a category 1 agent; 49% of women filled at least one prescription for an anticonvulsant medication during the study period.

Exposure to all antipsychotics was independently associated with a 35% increased risk for breast cancer (adjusted hazard ratio, 1.35; 95% CI, 1.14-1.61), the study team found.

Compared with anticonvulsants or lithium, the risk for breast cancer was significantly increased for high prolactin (category 1) antipsychotics (adjusted hazard ratio, 1.62; 95% CI, 1.30-2.03) and for mid-prolactin (category 2) drugs (aHR 1.54; 95% CI, 1.19-1.99), with no increased risk for category 3 antipsychotics.

“Our research is obviously of interest for preventing breast cancer in antipsychotic-treated patients. Checking a blood prolactin level is cheap and easy [and a high level is] fairly simple to mitigate,” said Dr. Rahman.
 

A matter of debate

Reached for comment, Christoph Correll, MD, professor of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said, “The potential elevation of breast cancer risk depending on the dose and time of treatment with antipsychotic medications with varying degrees of prolactin-raising properties has been a topic of research and matter of debate.”

This new study “adds another data point indicating that antipsychotics that are associated on average with a higher prolactin-raising effect than other antipsychotics may increase the risk of breast cancer in women to some degree,” said Dr. Correll, who was not involved with the study.

However, he cautioned that “naturalistic data are always vulnerable to residual confounding, for example, unmeasured effects that could also at least partially explain the results, and the follow-up time of only 4 years (maximum 6 years) in this study was relatively short.

“Nevertheless, given availability of many different antipsychotics with varying degrees of prolactin-raising potential, in women requiring antipsychotic treatment, less prolactin-raising antipsychotics may be preferable,” Dr. Correll said.

“In women receiving prolactin-raising antipsychotics for medium- and longer-term maintenance therapy, prolactin levels should be monitored,” he added.

When an elevated prolactin level is detected, this should be addressed “either via dose reduction, a switch to an alternative antipsychotic that does not raise prolactin levels significantly, or the addition of a partial or full D2 agonist when the prolactin-raising antipsychotic should be continued based on individualized risk assessment,” Dr. Correll advised.

This work was supported by an award from the Alvin J. Siteman Cancer Center; the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health; the Taylor Family Institute for Innovative Psychiatric Research; and the Center for Brain Research in Mood Disorders. The authors have disclosed no relevant financial relationships. Dr. Correll has received royalties from UpToDate and is a stock option holder of LB Pharma.

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

New research provides more evidence that antipsychotics that raise prolactin levels are tied to a significantly increased risk for breast cancer.

The relative risk for breast cancer was 62% higher in women who took category 1 antipsychotic medications associated with high prolactin levels. These include haloperidol (Haldol), paliperidone (Invega), and risperidone (Risperdal). Additionally, the risk was 54% higher in those taking category 2 antipsychotics that have mid-range effects on prolactin. These include iloperidone (Fanapt), lurasidone (Latuda), and olanzapine (Zyprexa).

In contrast, category 3 antipsychotics which have a lesser effect on prolactin levels were not associated with any increase in breast cancer risk. These drugs include aripiprazole (Abilify), asenapine (Saphris), brexpiprazole (Rexulti), cariprazine (Vraylar), clozapine (multiple brands), quetiapine (Seroquel), and ziprasidone (Geodon).

While the “absolute” breast cancer risk for these drugs is unclear, “we can make the case that high circulating prolactin levels are associated with breast cancer risk. This follows what is already known about prolactin from prior studies, notably the nurses’ health studies,” Tahir Rahman, MD, associate professor of psychiatry, Washington University School of Medicine, St. Louis, told this news organization.

“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr. Rahman added in a news release.

The study was published online Dec. 3 in the Journal of Clinical Psychopharmacology.
 

Test prolactin levels

Using administrative claims data, the researchers evaluated breast cancer risk in women aged 18-64 exposed to antipsychotic medications compared with anticonvulsants and/or lithium. 

They identified 914 cases of invasive breast cancer among 540,737 women.

Roughly 52% of the study population filled at least one prescription for a category 3 antipsychotic agent, whereas 15% filled at least one prescription for a category 1 agent; 49% of women filled at least one prescription for an anticonvulsant medication during the study period.

Exposure to all antipsychotics was independently associated with a 35% increased risk for breast cancer (adjusted hazard ratio, 1.35; 95% CI, 1.14-1.61), the study team found.

Compared with anticonvulsants or lithium, the risk for breast cancer was significantly increased for high prolactin (category 1) antipsychotics (adjusted hazard ratio, 1.62; 95% CI, 1.30-2.03) and for mid-prolactin (category 2) drugs (aHR 1.54; 95% CI, 1.19-1.99), with no increased risk for category 3 antipsychotics.

“Our research is obviously of interest for preventing breast cancer in antipsychotic-treated patients. Checking a blood prolactin level is cheap and easy [and a high level is] fairly simple to mitigate,” said Dr. Rahman.
 

A matter of debate

Reached for comment, Christoph Correll, MD, professor of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said, “The potential elevation of breast cancer risk depending on the dose and time of treatment with antipsychotic medications with varying degrees of prolactin-raising properties has been a topic of research and matter of debate.”

This new study “adds another data point indicating that antipsychotics that are associated on average with a higher prolactin-raising effect than other antipsychotics may increase the risk of breast cancer in women to some degree,” said Dr. Correll, who was not involved with the study.

However, he cautioned that “naturalistic data are always vulnerable to residual confounding, for example, unmeasured effects that could also at least partially explain the results, and the follow-up time of only 4 years (maximum 6 years) in this study was relatively short.

“Nevertheless, given availability of many different antipsychotics with varying degrees of prolactin-raising potential, in women requiring antipsychotic treatment, less prolactin-raising antipsychotics may be preferable,” Dr. Correll said.

“In women receiving prolactin-raising antipsychotics for medium- and longer-term maintenance therapy, prolactin levels should be monitored,” he added.

When an elevated prolactin level is detected, this should be addressed “either via dose reduction, a switch to an alternative antipsychotic that does not raise prolactin levels significantly, or the addition of a partial or full D2 agonist when the prolactin-raising antipsychotic should be continued based on individualized risk assessment,” Dr. Correll advised.

This work was supported by an award from the Alvin J. Siteman Cancer Center; the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health; the Taylor Family Institute for Innovative Psychiatric Research; and the Center for Brain Research in Mood Disorders. The authors have disclosed no relevant financial relationships. Dr. Correll has received royalties from UpToDate and is a stock option holder of LB Pharma.

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

Black women with metastatic triple-negative breast cancer (mTNBC) have outcomes in response to the antibody–drug conjugate sacituzumab govitecan (SG) (Trodelvy, Gilead) comparable to those of the overall patient population, with the drug showing similar efficacy and safety, shows a prespecified analysis of ASCENT.

A heterogenous disease with few treatment options and poor outcomes, mTNBC has an incidence rate twice as high in Black as in White women.

Black women with mTNBC may also experience worse outcomes than other groups, with a greater risk of mortality related to disparities in access to health care and in income, delays in treatment, a higher prevalence of comorbidities, and differences in tumor biology.

Previously presented data from the phase 3 ASCENT trial showed that SG nearly doubled overall survival versus single-agent chemotherapy in pretreated women with mTNBC, with the benefit observed across patient subgroups.

Based on these findings, the Food and Drug Administration approved SG for patients with mTNBC who have received at least two prior chemotherapies, at least one of which is to have been given in the metastatic setting.

Now, an analysis of the ASCENT data in just over 60 Black women with mTNBC showed that they can expect to see their progression-free survival (PFS) improve by 56% and their overall survival increase by a nonsignificant 36% when given SG as opposed to single-agent chemotherapy.

The research (abstract P5-16-07) was presented at the San Antonio Breast Cancer Symposium on Dec. 10.

The team says that Black women with mTNBC “derived a similar clinical benefit” from SG versus chemotherapy to other women in the study, and had a “manageable” safety profile, which was “consistent with the full trial population.”

Consequently, SG “should be considered a treatment option for Black patients with mTNBC who have received ≥ 2 prior chemotherapies,” at least one of which having been given in the metastatic setting.

Lead researcher Lisa A. Carey, MD, told this news organiztion that it is “very important” to show that the drug works in Black patients, adding: “We know that certain drugs don’t perform so well and it’s also true that people of color are particularly affected by TNBC.”

She said there were “only 62” Black patients in ASCENT, “so if you look at the entire trial and make assumptions that the drug performs the same in all the subsets, then sometimes you’re wrong.”

Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said there is “emerging interest” in racial disparities in cancer outcomes.

“Black patients have more trouble with access to care,” she said, noting that “in trial populations, [the outcomes] generally seem similar because the patients who go onto the trials tend to be those that can participate, but you never know until you look.”

Overall, Dr. Carey said the current results suggest that, “at least from the standpoint of the therapeutic implications of this drug – which is really a pretty remarkable drug in the overall study – it behaves very similarly in this group.”

Jennifer K. Litton, MD, vice president of clinical research at University of Texas MD Anderson Cancer Center, Houston, said: “We have known that minority patients, especially Black patients, have a higher rate of triple negative breast cancer and aggressive biologies, and have had worse breast cancer outcomes in many published series.”

She told this news organization that, “additionally, they are often underrepresented in breast cancer clinical trials.”

Dr. Litton said “the very favorable outcomes” reported in “this important subset of patients who participated in the ASCENT trial” confirm the use of SG in patients with mTNBC.

To examine the clinical outcomes of Black patients in the ASCENT study, the team conduced a prespecified analysis of participants self-reporting Black race who had been randomized to SG or single-agent chemotherapy of physician’s choice, including those with and without brain metastases.

Of the 529 patients enrolled to ASCENT, 62 (12%) were Black, of whom 28 were assigned to SG and 34 to single agent chemotherapy. The two groups were generally well balanced, although six patients in the chemotherapy arm had known brain metastases at baseline versus none of those given SG.

After a median treatment duration of 5.3 months with SG and 1.6 months for single-agent chemotherapy, there was a significant improvement in PFS with SG, at 5.4 months versus 2.2 months for chemotherapy, and a hazard ratio of 0.44 (P = .008).

There was also a nonsignificant improvement in overall survival with SG at 13.8 months versus 8.5 months for chemotherapy, and a hazard ratio of 0.64 (P = .159).

The objective response rate was 32% with SG versus 6% in patients given chemotherapy, while the median duration of response was 9.2 months in the SG arm and not evaluable for chemotherapy.

The researchers note that these efficacy findings were “consistent” with those seen in the full ASCENT study population.

In terms of safety, the most common treatment-related adverse events were neutropenia, seen in 64% of SG and 61% of chemotherapy patients, diarrhea in 64% and 13%, respectively, and fatigue, in 52% and 39%, respectively.

The most common grade ≥3 events were neutropenia, in 48% and 42% of SG and chemotherapy patients, respectively, followed by anemia, in 12% and 6%, respectively, leukopenia in 8% and 16%, respectively, and febrile neutropenia in 8% and 3%, respectively.

No treatment-related deaths occurred in either treatment arm.

Dose reduction due to treatment-emergent adverse events was recorded in 28% of patients receiving SG and 35% of those assigned to single-agent chemotherapy, and discontinuations occurred in 0% and 3%, respectively.

The study was sponsored by Gilead Sciences. Dr. Carey reports research funding from Sanofi, Novartis, Genentech/Roche, and GSK; spouse serves on the board of Falcon Therapeutics.

Black women with metastatic triple-negative breast cancer (mTNBC) have outcomes in response to the antibody–drug conjugate sacituzumab govitecan (SG) (Trodelvy, Gilead) comparable to those of the overall patient population, with the drug showing similar efficacy and safety, shows a prespecified analysis of ASCENT.

A heterogenous disease with few treatment options and poor outcomes, mTNBC has an incidence rate twice as high in Black as in White women.

Black women with mTNBC may also experience worse outcomes than other groups, with a greater risk of mortality related to disparities in access to health care and in income, delays in treatment, a higher prevalence of comorbidities, and differences in tumor biology.

Previously presented data from the phase 3 ASCENT trial showed that SG nearly doubled overall survival versus single-agent chemotherapy in pretreated women with mTNBC, with the benefit observed across patient subgroups.

Based on these findings, the Food and Drug Administration approved SG for patients with mTNBC who have received at least two prior chemotherapies, at least one of which is to have been given in the metastatic setting.

Now, an analysis of the ASCENT data in just over 60 Black women with mTNBC showed that they can expect to see their progression-free survival (PFS) improve by 56% and their overall survival increase by a nonsignificant 36% when given SG as opposed to single-agent chemotherapy.

The research (abstract P5-16-07) was presented at the San Antonio Breast Cancer Symposium on Dec. 10.

The team says that Black women with mTNBC “derived a similar clinical benefit” from SG versus chemotherapy to other women in the study, and had a “manageable” safety profile, which was “consistent with the full trial population.”

Consequently, SG “should be considered a treatment option for Black patients with mTNBC who have received ≥ 2 prior chemotherapies,” at least one of which having been given in the metastatic setting.

Lead researcher Lisa A. Carey, MD, told this news organiztion that it is “very important” to show that the drug works in Black patients, adding: “We know that certain drugs don’t perform so well and it’s also true that people of color are particularly affected by TNBC.”

She said there were “only 62” Black patients in ASCENT, “so if you look at the entire trial and make assumptions that the drug performs the same in all the subsets, then sometimes you’re wrong.”

Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said there is “emerging interest” in racial disparities in cancer outcomes.

“Black patients have more trouble with access to care,” she said, noting that “in trial populations, [the outcomes] generally seem similar because the patients who go onto the trials tend to be those that can participate, but you never know until you look.”

Overall, Dr. Carey said the current results suggest that, “at least from the standpoint of the therapeutic implications of this drug – which is really a pretty remarkable drug in the overall study – it behaves very similarly in this group.”

Jennifer K. Litton, MD, vice president of clinical research at University of Texas MD Anderson Cancer Center, Houston, said: “We have known that minority patients, especially Black patients, have a higher rate of triple negative breast cancer and aggressive biologies, and have had worse breast cancer outcomes in many published series.”

She told this news organization that, “additionally, they are often underrepresented in breast cancer clinical trials.”

Dr. Litton said “the very favorable outcomes” reported in “this important subset of patients who participated in the ASCENT trial” confirm the use of SG in patients with mTNBC.

To examine the clinical outcomes of Black patients in the ASCENT study, the team conduced a prespecified analysis of participants self-reporting Black race who had been randomized to SG or single-agent chemotherapy of physician’s choice, including those with and without brain metastases.

Of the 529 patients enrolled to ASCENT, 62 (12%) were Black, of whom 28 were assigned to SG and 34 to single agent chemotherapy. The two groups were generally well balanced, although six patients in the chemotherapy arm had known brain metastases at baseline versus none of those given SG.

After a median treatment duration of 5.3 months with SG and 1.6 months for single-agent chemotherapy, there was a significant improvement in PFS with SG, at 5.4 months versus 2.2 months for chemotherapy, and a hazard ratio of 0.44 (P = .008).

There was also a nonsignificant improvement in overall survival with SG at 13.8 months versus 8.5 months for chemotherapy, and a hazard ratio of 0.64 (P = .159).

The objective response rate was 32% with SG versus 6% in patients given chemotherapy, while the median duration of response was 9.2 months in the SG arm and not evaluable for chemotherapy.

The researchers note that these efficacy findings were “consistent” with those seen in the full ASCENT study population.

In terms of safety, the most common treatment-related adverse events were neutropenia, seen in 64% of SG and 61% of chemotherapy patients, diarrhea in 64% and 13%, respectively, and fatigue, in 52% and 39%, respectively.

The most common grade ≥3 events were neutropenia, in 48% and 42% of SG and chemotherapy patients, respectively, followed by anemia, in 12% and 6%, respectively, leukopenia in 8% and 16%, respectively, and febrile neutropenia in 8% and 3%, respectively.

No treatment-related deaths occurred in either treatment arm.

Dose reduction due to treatment-emergent adverse events was recorded in 28% of patients receiving SG and 35% of those assigned to single-agent chemotherapy, and discontinuations occurred in 0% and 3%, respectively.

The study was sponsored by Gilead Sciences. Dr. Carey reports research funding from Sanofi, Novartis, Genentech/Roche, and GSK; spouse serves on the board of Falcon Therapeutics.

Black women with metastatic triple-negative breast cancer (mTNBC) have outcomes in response to the antibody–drug conjugate sacituzumab govitecan (SG) (Trodelvy, Gilead) comparable to those of the overall patient population, with the drug showing similar efficacy and safety, shows a prespecified analysis of ASCENT.

A heterogenous disease with few treatment options and poor outcomes, mTNBC has an incidence rate twice as high in Black as in White women.

Black women with mTNBC may also experience worse outcomes than other groups, with a greater risk of mortality related to disparities in access to health care and in income, delays in treatment, a higher prevalence of comorbidities, and differences in tumor biology.

Previously presented data from the phase 3 ASCENT trial showed that SG nearly doubled overall survival versus single-agent chemotherapy in pretreated women with mTNBC, with the benefit observed across patient subgroups.

Based on these findings, the Food and Drug Administration approved SG for patients with mTNBC who have received at least two prior chemotherapies, at least one of which is to have been given in the metastatic setting.

Now, an analysis of the ASCENT data in just over 60 Black women with mTNBC showed that they can expect to see their progression-free survival (PFS) improve by 56% and their overall survival increase by a nonsignificant 36% when given SG as opposed to single-agent chemotherapy.

The research (abstract P5-16-07) was presented at the San Antonio Breast Cancer Symposium on Dec. 10.

The team says that Black women with mTNBC “derived a similar clinical benefit” from SG versus chemotherapy to other women in the study, and had a “manageable” safety profile, which was “consistent with the full trial population.”

Consequently, SG “should be considered a treatment option for Black patients with mTNBC who have received ≥ 2 prior chemotherapies,” at least one of which having been given in the metastatic setting.

Lead researcher Lisa A. Carey, MD, told this news organiztion that it is “very important” to show that the drug works in Black patients, adding: “We know that certain drugs don’t perform so well and it’s also true that people of color are particularly affected by TNBC.”

She said there were “only 62” Black patients in ASCENT, “so if you look at the entire trial and make assumptions that the drug performs the same in all the subsets, then sometimes you’re wrong.”

Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said there is “emerging interest” in racial disparities in cancer outcomes.

“Black patients have more trouble with access to care,” she said, noting that “in trial populations, [the outcomes] generally seem similar because the patients who go onto the trials tend to be those that can participate, but you never know until you look.”

Overall, Dr. Carey said the current results suggest that, “at least from the standpoint of the therapeutic implications of this drug – which is really a pretty remarkable drug in the overall study – it behaves very similarly in this group.”

Jennifer K. Litton, MD, vice president of clinical research at University of Texas MD Anderson Cancer Center, Houston, said: “We have known that minority patients, especially Black patients, have a higher rate of triple negative breast cancer and aggressive biologies, and have had worse breast cancer outcomes in many published series.”

She told this news organization that, “additionally, they are often underrepresented in breast cancer clinical trials.”

Dr. Litton said “the very favorable outcomes” reported in “this important subset of patients who participated in the ASCENT trial” confirm the use of SG in patients with mTNBC.

To examine the clinical outcomes of Black patients in the ASCENT study, the team conduced a prespecified analysis of participants self-reporting Black race who had been randomized to SG or single-agent chemotherapy of physician’s choice, including those with and without brain metastases.

Of the 529 patients enrolled to ASCENT, 62 (12%) were Black, of whom 28 were assigned to SG and 34 to single agent chemotherapy. The two groups were generally well balanced, although six patients in the chemotherapy arm had known brain metastases at baseline versus none of those given SG.

After a median treatment duration of 5.3 months with SG and 1.6 months for single-agent chemotherapy, there was a significant improvement in PFS with SG, at 5.4 months versus 2.2 months for chemotherapy, and a hazard ratio of 0.44 (P = .008).

There was also a nonsignificant improvement in overall survival with SG at 13.8 months versus 8.5 months for chemotherapy, and a hazard ratio of 0.64 (P = .159).

The objective response rate was 32% with SG versus 6% in patients given chemotherapy, while the median duration of response was 9.2 months in the SG arm and not evaluable for chemotherapy.

The researchers note that these efficacy findings were “consistent” with those seen in the full ASCENT study population.

In terms of safety, the most common treatment-related adverse events were neutropenia, seen in 64% of SG and 61% of chemotherapy patients, diarrhea in 64% and 13%, respectively, and fatigue, in 52% and 39%, respectively.

The most common grade ≥3 events were neutropenia, in 48% and 42% of SG and chemotherapy patients, respectively, followed by anemia, in 12% and 6%, respectively, leukopenia in 8% and 16%, respectively, and febrile neutropenia in 8% and 3%, respectively.

No treatment-related deaths occurred in either treatment arm.

Dose reduction due to treatment-emergent adverse events was recorded in 28% of patients receiving SG and 35% of those assigned to single-agent chemotherapy, and discontinuations occurred in 0% and 3%, respectively.

The study was sponsored by Gilead Sciences. Dr. Carey reports research funding from Sanofi, Novartis, Genentech/Roche, and GSK; spouse serves on the board of Falcon Therapeutics.

The cutoff for programmed death–ligand 1 (PD-L1) combined positive score (CPS) of at least 10 for using pembrolizumab (Keytruda) to treat metastatic triple-negative breast cancer (mTNBC) is able to identify patients who are expected to derive most benefit, shows an analysis of KEYNOTE-355 recently presented at the San Antonio Breast Cancer Symposium.

Patients enrolled in KEYNOTE-355 – which is a phase 3, placebo-controlled trial of 847 patients – were stratified by CPS scores of at least 1 and at least 10, with the latter group in which adding pembrolizumab to chemotherapy was shown to significantly improve both overall survival and progression-free survival.

As it was unclear whether taking a more fine-grained approach would reveal specific CPS scores at which pembrolizumab would be beneficial, Javier Cortes, MD, PhD, International Breast Cancer Center, Barcelona, and colleagues divided the patients into four CPS levels: less than 1, 1-9, 10-19, and at least 20.

Patients with a CPS 10-19 and at least 20 given pembrolizumab alongside chemotherapy had an overall survival benefit of 29% and 28%, respectively, while the PFS improvement was 30% and 38%. In the CPS of less than 1 and 1-9 groups, there were no discernible benefits from adding the checkpoint inhibitor.

“Given the similar outcomes in the CPS 10-19 and the CPS ≥20 subgroups, a CPS of 10 or more is a reasonable cutoff to define the population of patients with metastatic TNBC that might have benefit from the addition of pembrolizumab to chemotherapy,” Dr. Cortes said. “In my opinion, these results provide further support for pembrolizumab in combination with chemotherapy as a good option, maybe a standard of care for some patients ... with local recurrent unresectable or metastatic TNBC whose tumors express PD-1 CPS ≥10.”

Invited discussant Hope S. Rugo, MD, said the study demonstrates that PD-L1 CPS of at least 10 is “clearly the optimal cutoff for differentiating benefit from pembrolizumab” and confirms the combination with chemotherapy as a “standard of care in this population”.

However, there are a number of outstanding questions in the metastatic setting, she said, including the test used to determine PD-L1 expression.

“Clearly the test that you order should be matched to the planned checkpoint inhibitor, and we look forward to additional data” on the relative overlap of the assays used in both the current study and in KEYNOTE-522.

However, IMpassion130 showed there is “incomplete overlap in terms of the two antibodies and tests that have been used to define PD-L1 positivity in breast cancer,” said Dr. Rugo, professor of medicine in hematology and oncology at the University of California, San Francisco.

“For excellent responders, can chemotherapy and eventually immunotherapy be discontinued, and when is it optimal? How long should we be continuing the combination and how long should we continue the checkpoint inhibitor alone?” she asked.

“Certainly in my own clinical practice,” Dr. Rugo explained, “in those excellent responders, it’s difficult to know when to stop the checkpoint inhibitor, but sometimes toxicity tells us the answer to that question. At some point, we need to stop therapy and understand what happens to those patients.”

She said that only 38% of patients in the current study benefited from pembrolizumab. “How can we amplify the immune response in those patients who do not have PD-L1–positive disease to further extend this benefit, and can we extend the efficacy to other subtypes? There are ongoing studies evaluating this question,” Dr. Rugo said.

Dr. Cortes said that KEYNOTE-355 showed the addition of pembrolizumab to chemotherapy led to clinically meaningful improvements in both PFS and overall survival versus chemotherapy alone in the first-line treatment of mTNBC.

However, that benefit was seen only in patients with a PD-L1 CPS of at least 10, while there was no statistically significant improvement in either PFS or overall survival in those with a CPS of at least 1.

He explained that 847 patients with previously untreated locally recurrent or metastatic TNBC, or those who had been treated at least 6 months prior to disease recurrence, were randomized 2:1 to pembrolizumab or placebo plus chemotherapy.

For the current analysis, they substratified patients by PD-L1 CPS into less than 1, which accounted for 24.9% of patients; 1-9, seen in 36.2%-38.4%; 10-19, accounting for 13.9%-14.1%; and at least 20, seen in 22.8%-24.7% of patients.

Dr. Cortes said the overall survival rate among patients with CPS of at least 10 was 70.5% for patients treated with pembrolizumab plus chemotherapy versus 81.6% for those assigned to placebo, at a significant hazard ratio of 0.73 (P = .0093).

Among patients with CPS of at least 1, the overall survival rate was 79.1% with pembrolizumab plus chemotherapy and 83.9% in those given placebo, at a nonsignificant hazard ratio of 0.86. This translated into an HR of 0.89 in the intention-to-treat analysis.

Turning to the novel subgroups, Dr. Cortes showed that the HR for overall survival for pembrolizumab versus placebo was nonsignificant in patients with CPS of at least 1, at 0.97, and in those with CPS 1-9, at 1.09.

However, the HRs were markedly improved in patients with CPD 10-19, at 0.71, and in those with CPS of at least 20, at 0.72, showing that the “relative benefit of adding pembrolizumab to chemotherapy was pretty much the same ... suggesting that CPS ≥10 could be a reasonable cutoff.”

In both of these groups, there was a sustained separation in the overall survival curves starting at around 10 months.

Turning to the PFS results, Dr Cortes said the event-free rate was 65.5% with the addition of pembrolizumab to chemotherapy in patients with PD-L1 CPS of at least 10, while those given placebo had a rate of 78.6%, at an HR of 0.66.

In patients with PD-L1 CPS of at least 1, the HR was 0.75, or 0.82 in the intention-to-treat analysis.

“As with overall survival,” he said, there was a “trend toward improved efficacy with PD-L1 enrichment with the addition of pembrolizumab to chemotherapy, although the PFS benefit in the pembro arm was slightly greater in the CPS ≥20 subgroup, compared to the CPS 10-19 subgroup.”

However, they highlighted that the difference was “small and the confidence intervals clearly overlapped.”

Why does PD-L1 expression play a role in response to pembrolizumab in mTNBC, but not in the early disease setting as seen in KEYNOTE-522?

“This is a question we have raised many, many times and have had many debates on,” Dr. Cortes said. “They are two completely different populations with the early breast cancer setting completely different to that in metastatic disease. Maybe the microenvironment plays a different role there, maybe we have to explore more in detail other biomarkers. I also think that different drugs were used in the neoadjuvant setting. We still have many unanswered questions.”

Dr. Rugo suggested that previous studies have given some clues to these questions with reductions in PD-L1 expression and tumor-infiltrating leukocytes observed between primary and metastatic disease.

The immune differences between primary and metastatic disease lead to immune escape, she said, adding: “This is clearly complicated by mutational complexity under the pressure of treatment.”

The study was funded by Merck Sharp and Dohme. Dr. Cortes and Dr. Rugo reported relationships with numerous pharmaceutical companies.

The cutoff for programmed death–ligand 1 (PD-L1) combined positive score (CPS) of at least 10 for using pembrolizumab (Keytruda) to treat metastatic triple-negative breast cancer (mTNBC) is able to identify patients who are expected to derive most benefit, shows an analysis of KEYNOTE-355 recently presented at the San Antonio Breast Cancer Symposium.

Patients enrolled in KEYNOTE-355 – which is a phase 3, placebo-controlled trial of 847 patients – were stratified by CPS scores of at least 1 and at least 10, with the latter group in which adding pembrolizumab to chemotherapy was shown to significantly improve both overall survival and progression-free survival.

As it was unclear whether taking a more fine-grained approach would reveal specific CPS scores at which pembrolizumab would be beneficial, Javier Cortes, MD, PhD, International Breast Cancer Center, Barcelona, and colleagues divided the patients into four CPS levels: less than 1, 1-9, 10-19, and at least 20.

Patients with a CPS 10-19 and at least 20 given pembrolizumab alongside chemotherapy had an overall survival benefit of 29% and 28%, respectively, while the PFS improvement was 30% and 38%. In the CPS of less than 1 and 1-9 groups, there were no discernible benefits from adding the checkpoint inhibitor.

“Given the similar outcomes in the CPS 10-19 and the CPS ≥20 subgroups, a CPS of 10 or more is a reasonable cutoff to define the population of patients with metastatic TNBC that might have benefit from the addition of pembrolizumab to chemotherapy,” Dr. Cortes said. “In my opinion, these results provide further support for pembrolizumab in combination with chemotherapy as a good option, maybe a standard of care for some patients ... with local recurrent unresectable or metastatic TNBC whose tumors express PD-1 CPS ≥10.”

Invited discussant Hope S. Rugo, MD, said the study demonstrates that PD-L1 CPS of at least 10 is “clearly the optimal cutoff for differentiating benefit from pembrolizumab” and confirms the combination with chemotherapy as a “standard of care in this population”.

However, there are a number of outstanding questions in the metastatic setting, she said, including the test used to determine PD-L1 expression.

“Clearly the test that you order should be matched to the planned checkpoint inhibitor, and we look forward to additional data” on the relative overlap of the assays used in both the current study and in KEYNOTE-522.

However, IMpassion130 showed there is “incomplete overlap in terms of the two antibodies and tests that have been used to define PD-L1 positivity in breast cancer,” said Dr. Rugo, professor of medicine in hematology and oncology at the University of California, San Francisco.

“For excellent responders, can chemotherapy and eventually immunotherapy be discontinued, and when is it optimal? How long should we be continuing the combination and how long should we continue the checkpoint inhibitor alone?” she asked.

“Certainly in my own clinical practice,” Dr. Rugo explained, “in those excellent responders, it’s difficult to know when to stop the checkpoint inhibitor, but sometimes toxicity tells us the answer to that question. At some point, we need to stop therapy and understand what happens to those patients.”

She said that only 38% of patients in the current study benefited from pembrolizumab. “How can we amplify the immune response in those patients who do not have PD-L1–positive disease to further extend this benefit, and can we extend the efficacy to other subtypes? There are ongoing studies evaluating this question,” Dr. Rugo said.

Dr. Cortes said that KEYNOTE-355 showed the addition of pembrolizumab to chemotherapy led to clinically meaningful improvements in both PFS and overall survival versus chemotherapy alone in the first-line treatment of mTNBC.

However, that benefit was seen only in patients with a PD-L1 CPS of at least 10, while there was no statistically significant improvement in either PFS or overall survival in those with a CPS of at least 1.

He explained that 847 patients with previously untreated locally recurrent or metastatic TNBC, or those who had been treated at least 6 months prior to disease recurrence, were randomized 2:1 to pembrolizumab or placebo plus chemotherapy.

For the current analysis, they substratified patients by PD-L1 CPS into less than 1, which accounted for 24.9% of patients; 1-9, seen in 36.2%-38.4%; 10-19, accounting for 13.9%-14.1%; and at least 20, seen in 22.8%-24.7% of patients.

Dr. Cortes said the overall survival rate among patients with CPS of at least 10 was 70.5% for patients treated with pembrolizumab plus chemotherapy versus 81.6% for those assigned to placebo, at a significant hazard ratio of 0.73 (P = .0093).

Among patients with CPS of at least 1, the overall survival rate was 79.1% with pembrolizumab plus chemotherapy and 83.9% in those given placebo, at a nonsignificant hazard ratio of 0.86. This translated into an HR of 0.89 in the intention-to-treat analysis.

Turning to the novel subgroups, Dr. Cortes showed that the HR for overall survival for pembrolizumab versus placebo was nonsignificant in patients with CPS of at least 1, at 0.97, and in those with CPS 1-9, at 1.09.

However, the HRs were markedly improved in patients with CPD 10-19, at 0.71, and in those with CPS of at least 20, at 0.72, showing that the “relative benefit of adding pembrolizumab to chemotherapy was pretty much the same ... suggesting that CPS ≥10 could be a reasonable cutoff.”

In both of these groups, there was a sustained separation in the overall survival curves starting at around 10 months.

Turning to the PFS results, Dr Cortes said the event-free rate was 65.5% with the addition of pembrolizumab to chemotherapy in patients with PD-L1 CPS of at least 10, while those given placebo had a rate of 78.6%, at an HR of 0.66.

In patients with PD-L1 CPS of at least 1, the HR was 0.75, or 0.82 in the intention-to-treat analysis.

“As with overall survival,” he said, there was a “trend toward improved efficacy with PD-L1 enrichment with the addition of pembrolizumab to chemotherapy, although the PFS benefit in the pembro arm was slightly greater in the CPS ≥20 subgroup, compared to the CPS 10-19 subgroup.”

However, they highlighted that the difference was “small and the confidence intervals clearly overlapped.”

Why does PD-L1 expression play a role in response to pembrolizumab in mTNBC, but not in the early disease setting as seen in KEYNOTE-522?

“This is a question we have raised many, many times and have had many debates on,” Dr. Cortes said. “They are two completely different populations with the early breast cancer setting completely different to that in metastatic disease. Maybe the microenvironment plays a different role there, maybe we have to explore more in detail other biomarkers. I also think that different drugs were used in the neoadjuvant setting. We still have many unanswered questions.”

Dr. Rugo suggested that previous studies have given some clues to these questions with reductions in PD-L1 expression and tumor-infiltrating leukocytes observed between primary and metastatic disease.

The immune differences between primary and metastatic disease lead to immune escape, she said, adding: “This is clearly complicated by mutational complexity under the pressure of treatment.”

The study was funded by Merck Sharp and Dohme. Dr. Cortes and Dr. Rugo reported relationships with numerous pharmaceutical companies.

The cutoff for programmed death–ligand 1 (PD-L1) combined positive score (CPS) of at least 10 for using pembrolizumab (Keytruda) to treat metastatic triple-negative breast cancer (mTNBC) is able to identify patients who are expected to derive most benefit, shows an analysis of KEYNOTE-355 recently presented at the San Antonio Breast Cancer Symposium.

Patients enrolled in KEYNOTE-355 – which is a phase 3, placebo-controlled trial of 847 patients – were stratified by CPS scores of at least 1 and at least 10, with the latter group in which adding pembrolizumab to chemotherapy was shown to significantly improve both overall survival and progression-free survival.

As it was unclear whether taking a more fine-grained approach would reveal specific CPS scores at which pembrolizumab would be beneficial, Javier Cortes, MD, PhD, International Breast Cancer Center, Barcelona, and colleagues divided the patients into four CPS levels: less than 1, 1-9, 10-19, and at least 20.

Patients with a CPS 10-19 and at least 20 given pembrolizumab alongside chemotherapy had an overall survival benefit of 29% and 28%, respectively, while the PFS improvement was 30% and 38%. In the CPS of less than 1 and 1-9 groups, there were no discernible benefits from adding the checkpoint inhibitor.

“Given the similar outcomes in the CPS 10-19 and the CPS ≥20 subgroups, a CPS of 10 or more is a reasonable cutoff to define the population of patients with metastatic TNBC that might have benefit from the addition of pembrolizumab to chemotherapy,” Dr. Cortes said. “In my opinion, these results provide further support for pembrolizumab in combination with chemotherapy as a good option, maybe a standard of care for some patients ... with local recurrent unresectable or metastatic TNBC whose tumors express PD-1 CPS ≥10.”

Invited discussant Hope S. Rugo, MD, said the study demonstrates that PD-L1 CPS of at least 10 is “clearly the optimal cutoff for differentiating benefit from pembrolizumab” and confirms the combination with chemotherapy as a “standard of care in this population”.

However, there are a number of outstanding questions in the metastatic setting, she said, including the test used to determine PD-L1 expression.

“Clearly the test that you order should be matched to the planned checkpoint inhibitor, and we look forward to additional data” on the relative overlap of the assays used in both the current study and in KEYNOTE-522.

However, IMpassion130 showed there is “incomplete overlap in terms of the two antibodies and tests that have been used to define PD-L1 positivity in breast cancer,” said Dr. Rugo, professor of medicine in hematology and oncology at the University of California, San Francisco.

“For excellent responders, can chemotherapy and eventually immunotherapy be discontinued, and when is it optimal? How long should we be continuing the combination and how long should we continue the checkpoint inhibitor alone?” she asked.

“Certainly in my own clinical practice,” Dr. Rugo explained, “in those excellent responders, it’s difficult to know when to stop the checkpoint inhibitor, but sometimes toxicity tells us the answer to that question. At some point, we need to stop therapy and understand what happens to those patients.”

She said that only 38% of patients in the current study benefited from pembrolizumab. “How can we amplify the immune response in those patients who do not have PD-L1–positive disease to further extend this benefit, and can we extend the efficacy to other subtypes? There are ongoing studies evaluating this question,” Dr. Rugo said.

Dr. Cortes said that KEYNOTE-355 showed the addition of pembrolizumab to chemotherapy led to clinically meaningful improvements in both PFS and overall survival versus chemotherapy alone in the first-line treatment of mTNBC.

However, that benefit was seen only in patients with a PD-L1 CPS of at least 10, while there was no statistically significant improvement in either PFS or overall survival in those with a CPS of at least 1.

He explained that 847 patients with previously untreated locally recurrent or metastatic TNBC, or those who had been treated at least 6 months prior to disease recurrence, were randomized 2:1 to pembrolizumab or placebo plus chemotherapy.

For the current analysis, they substratified patients by PD-L1 CPS into less than 1, which accounted for 24.9% of patients; 1-9, seen in 36.2%-38.4%; 10-19, accounting for 13.9%-14.1%; and at least 20, seen in 22.8%-24.7% of patients.

Dr. Cortes said the overall survival rate among patients with CPS of at least 10 was 70.5% for patients treated with pembrolizumab plus chemotherapy versus 81.6% for those assigned to placebo, at a significant hazard ratio of 0.73 (P = .0093).

Among patients with CPS of at least 1, the overall survival rate was 79.1% with pembrolizumab plus chemotherapy and 83.9% in those given placebo, at a nonsignificant hazard ratio of 0.86. This translated into an HR of 0.89 in the intention-to-treat analysis.

Turning to the novel subgroups, Dr. Cortes showed that the HR for overall survival for pembrolizumab versus placebo was nonsignificant in patients with CPS of at least 1, at 0.97, and in those with CPS 1-9, at 1.09.

However, the HRs were markedly improved in patients with CPD 10-19, at 0.71, and in those with CPS of at least 20, at 0.72, showing that the “relative benefit of adding pembrolizumab to chemotherapy was pretty much the same ... suggesting that CPS ≥10 could be a reasonable cutoff.”

In both of these groups, there was a sustained separation in the overall survival curves starting at around 10 months.

Turning to the PFS results, Dr Cortes said the event-free rate was 65.5% with the addition of pembrolizumab to chemotherapy in patients with PD-L1 CPS of at least 10, while those given placebo had a rate of 78.6%, at an HR of 0.66.

In patients with PD-L1 CPS of at least 1, the HR was 0.75, or 0.82 in the intention-to-treat analysis.

“As with overall survival,” he said, there was a “trend toward improved efficacy with PD-L1 enrichment with the addition of pembrolizumab to chemotherapy, although the PFS benefit in the pembro arm was slightly greater in the CPS ≥20 subgroup, compared to the CPS 10-19 subgroup.”

However, they highlighted that the difference was “small and the confidence intervals clearly overlapped.”

Why does PD-L1 expression play a role in response to pembrolizumab in mTNBC, but not in the early disease setting as seen in KEYNOTE-522?

“This is a question we have raised many, many times and have had many debates on,” Dr. Cortes said. “They are two completely different populations with the early breast cancer setting completely different to that in metastatic disease. Maybe the microenvironment plays a different role there, maybe we have to explore more in detail other biomarkers. I also think that different drugs were used in the neoadjuvant setting. We still have many unanswered questions.”

Dr. Rugo suggested that previous studies have given some clues to these questions with reductions in PD-L1 expression and tumor-infiltrating leukocytes observed between primary and metastatic disease.

The immune differences between primary and metastatic disease lead to immune escape, she said, adding: “This is clearly complicated by mutational complexity under the pressure of treatment.”

The study was funded by Merck Sharp and Dohme. Dr. Cortes and Dr. Rugo reported relationships with numerous pharmaceutical companies.

Tisagenlecleucel failed to outperform standard of care treatment when given as a second-line treatment for certain patients with relapsed/refractory aggressive non-Hodgkin lymphomas, according to results of a randomized, phase 3 trial.

The chimeric antigen receptor (CAR) T-cell therapy did not improve event-free survival (EFS) in this phase 3 BELINDA study, potentially because of study design decisions or imbalances in relevant patient characteristics, according to the study investigators.

Despite the negative result, insights from this study will inform the development of future clinical trials of CAR T-cell therapy, said BELINDA investigator Michael R. Bishop, MD, of the David and Etta Jonas Center for Cellular Therapy, University of Chicago.

Findings of BELINDA, presented at the annual meeting of the American Society of Hematology, stand in contrast to two other high-profile CAR T-cell therapy studies also presented at the meeting. Those other studies demonstrated significant improvements in EFS in the second-line treatment of large B-cell lymphomas.

“All of us are excited to see that the other two trials were positive, and we were hoping that ours would be as well, but there are significant differences in the trial design,” Dr. Bishop said in a press conference held at the ASH meeting.

Tisagenlecleucel (tisa-cel), an anti-CD19 CAR T-cell therapy, is already approved by the Food and Drug Administration for the treatment of patients with relapsed or refractory large B-cell lymphomas after at least two other lines of systemic therapy.

The aim of the pivotal phase 3, randomized, multicenter BELINDA study was to evaluate tisa-cel earlier in the course of treatment for patients with more aggressive disease, according to Dr. Bishop.

About two-thirds of non-Hodgkin lymphoma patients will be cured with first-line treatment. However, very poor outcomes are seen among patients with disease that does not respond to the initial treatment or that reoccurs shortly afterward, Dr. Bishop said.

The standard of care approach for those patients is second-line therapy, he noted, usually with combination chemoimmunotherapy, followed by autologous stem cell transplant if the disease responds to chemotherapy.

“Unfortunately, only a minority of those patients will be found to have chemotherapy-sensitive disease and be able to go on to autologous stem cell transplantation,” Dr. Bishop said. “And even in that subgroup of patients, the outcomes are relatively poor.”

Accordingly, the phase 3 BELINDA study enrolled patients with aggressive non-Hodgkin lymphomas that either did not respond to first-line treatment or that reoccurred within 12 months.

The primary endpoint of the study was EFS, defined as the time from randomization to either stable or progressive disease at or after a week 12 assessment or to any-cause death at any time.

While that primary endpoint was not met for tisa-cel versus standard of care therapy, two other randomized, phase 3 studies presented at the ASH meeting did demonstrate that CAR T-cell therapy extended EFS when given as a second-line lymphoma treatment.

In the randomized, phase 3 ZUMA-7 trial, axicabtagene ciloleucel (axi-cel) significantly improved EFS versus standard of care in the treatment of patients with large B-cell lymphoma refractory to or relapsed within 12 months of adequate first-line therapy, according to investigators.

Similarly, the investigators said that treatment with lisocabtagene maraleucel (liso-cel) led to a significant improvement in EFS in TRANSFORM, a randomized, phase 3 clinical trial that enrolled patients with large B-cell lymphoma that was refractory to first-line therapy or else relapsed within 12 months of that treatment.

“It’s very possible that either or both the patient characteristics and the study design is what led to the difference in the top-line study results,” lymphoma specialist Andrew M. Evens, DO, said in an interview.

There were substantial differences between the studies in terms of what was allowed as optional bridging therapy and salvage therapy, according to Dr. Evens, associate director for clinical services and director of the lymphoma program at Rutgers Cancer Institute in New Brunswick, N.J.

“In ZUMA-7, they only allowed steroids as bridging therapy,” said Dr. Evens, who was not an investigator on any of the three second-line CAR T-cell studies.

In the BELINDA study, optional platinum-based chemotherapy bridging treatment allowed in one arm of the study could have potentially delayed tisa-cel infusion until after the week 6 assessment, study investigators reported in their ASH meeting abstract.

Differences in lymphodepleting therapy prior to CAR T-cell therapy could have also played a role. According to Dr. Bishop, the total doses of cyclophosphamide and fludarabine in BELINDA were 900 mg/m2 and 75 mg/m2, respectively, while in the other two trials, doses were 1,500 mg/m² and 90 mg/m², respectively.

Lymphodepleting chemotherapy is “extremely important” in the success of CAR T-cell therapeutic approaches, he noted at the press conference.

Dr. Bishop reported receiving consultancy fees from Arcellx, Autolus Therapeutics, Bristol-Myers Squibb, CRISPR, Kite/Gilead, and Novartis. He also reported research funding from Bristol-Myers Squibb and Kite/Gilead.

Tisagenlecleucel failed to outperform standard of care treatment when given as a second-line treatment for certain patients with relapsed/refractory aggressive non-Hodgkin lymphomas, according to results of a randomized, phase 3 trial.

The chimeric antigen receptor (CAR) T-cell therapy did not improve event-free survival (EFS) in this phase 3 BELINDA study, potentially because of study design decisions or imbalances in relevant patient characteristics, according to the study investigators.

Despite the negative result, insights from this study will inform the development of future clinical trials of CAR T-cell therapy, said BELINDA investigator Michael R. Bishop, MD, of the David and Etta Jonas Center for Cellular Therapy, University of Chicago.

Findings of BELINDA, presented at the annual meeting of the American Society of Hematology, stand in contrast to two other high-profile CAR T-cell therapy studies also presented at the meeting. Those other studies demonstrated significant improvements in EFS in the second-line treatment of large B-cell lymphomas.

“All of us are excited to see that the other two trials were positive, and we were hoping that ours would be as well, but there are significant differences in the trial design,” Dr. Bishop said in a press conference held at the ASH meeting.

Tisagenlecleucel (tisa-cel), an anti-CD19 CAR T-cell therapy, is already approved by the Food and Drug Administration for the treatment of patients with relapsed or refractory large B-cell lymphomas after at least two other lines of systemic therapy.

The aim of the pivotal phase 3, randomized, multicenter BELINDA study was to evaluate tisa-cel earlier in the course of treatment for patients with more aggressive disease, according to Dr. Bishop.

About two-thirds of non-Hodgkin lymphoma patients will be cured with first-line treatment. However, very poor outcomes are seen among patients with disease that does not respond to the initial treatment or that reoccurs shortly afterward, Dr. Bishop said.

The standard of care approach for those patients is second-line therapy, he noted, usually with combination chemoimmunotherapy, followed by autologous stem cell transplant if the disease responds to chemotherapy.

“Unfortunately, only a minority of those patients will be found to have chemotherapy-sensitive disease and be able to go on to autologous stem cell transplantation,” Dr. Bishop said. “And even in that subgroup of patients, the outcomes are relatively poor.”

Accordingly, the phase 3 BELINDA study enrolled patients with aggressive non-Hodgkin lymphomas that either did not respond to first-line treatment or that reoccurred within 12 months.

The primary endpoint of the study was EFS, defined as the time from randomization to either stable or progressive disease at or after a week 12 assessment or to any-cause death at any time.

While that primary endpoint was not met for tisa-cel versus standard of care therapy, two other randomized, phase 3 studies presented at the ASH meeting did demonstrate that CAR T-cell therapy extended EFS when given as a second-line lymphoma treatment.

In the randomized, phase 3 ZUMA-7 trial, axicabtagene ciloleucel (axi-cel) significantly improved EFS versus standard of care in the treatment of patients with large B-cell lymphoma refractory to or relapsed within 12 months of adequate first-line therapy, according to investigators.

Similarly, the investigators said that treatment with lisocabtagene maraleucel (liso-cel) led to a significant improvement in EFS in TRANSFORM, a randomized, phase 3 clinical trial that enrolled patients with large B-cell lymphoma that was refractory to first-line therapy or else relapsed within 12 months of that treatment.

“It’s very possible that either or both the patient characteristics and the study design is what led to the difference in the top-line study results,” lymphoma specialist Andrew M. Evens, DO, said in an interview.

There were substantial differences between the studies in terms of what was allowed as optional bridging therapy and salvage therapy, according to Dr. Evens, associate director for clinical services and director of the lymphoma program at Rutgers Cancer Institute in New Brunswick, N.J.

“In ZUMA-7, they only allowed steroids as bridging therapy,” said Dr. Evens, who was not an investigator on any of the three second-line CAR T-cell studies.

In the BELINDA study, optional platinum-based chemotherapy bridging treatment allowed in one arm of the study could have potentially delayed tisa-cel infusion until after the week 6 assessment, study investigators reported in their ASH meeting abstract.

Differences in lymphodepleting therapy prior to CAR T-cell therapy could have also played a role. According to Dr. Bishop, the total doses of cyclophosphamide and fludarabine in BELINDA were 900 mg/m2 and 75 mg/m2, respectively, while in the other two trials, doses were 1,500 mg/m² and 90 mg/m², respectively.

Lymphodepleting chemotherapy is “extremely important” in the success of CAR T-cell therapeutic approaches, he noted at the press conference.

Dr. Bishop reported receiving consultancy fees from Arcellx, Autolus Therapeutics, Bristol-Myers Squibb, CRISPR, Kite/Gilead, and Novartis. He also reported research funding from Bristol-Myers Squibb and Kite/Gilead.

Tisagenlecleucel failed to outperform standard of care treatment when given as a second-line treatment for certain patients with relapsed/refractory aggressive non-Hodgkin lymphomas, according to results of a randomized, phase 3 trial.

The chimeric antigen receptor (CAR) T-cell therapy did not improve event-free survival (EFS) in this phase 3 BELINDA study, potentially because of study design decisions or imbalances in relevant patient characteristics, according to the study investigators.

Despite the negative result, insights from this study will inform the development of future clinical trials of CAR T-cell therapy, said BELINDA investigator Michael R. Bishop, MD, of the David and Etta Jonas Center for Cellular Therapy, University of Chicago.

Findings of BELINDA, presented at the annual meeting of the American Society of Hematology, stand in contrast to two other high-profile CAR T-cell therapy studies also presented at the meeting. Those other studies demonstrated significant improvements in EFS in the second-line treatment of large B-cell lymphomas.

“All of us are excited to see that the other two trials were positive, and we were hoping that ours would be as well, but there are significant differences in the trial design,” Dr. Bishop said in a press conference held at the ASH meeting.

Tisagenlecleucel (tisa-cel), an anti-CD19 CAR T-cell therapy, is already approved by the Food and Drug Administration for the treatment of patients with relapsed or refractory large B-cell lymphomas after at least two other lines of systemic therapy.

The aim of the pivotal phase 3, randomized, multicenter BELINDA study was to evaluate tisa-cel earlier in the course of treatment for patients with more aggressive disease, according to Dr. Bishop.

About two-thirds of non-Hodgkin lymphoma patients will be cured with first-line treatment. However, very poor outcomes are seen among patients with disease that does not respond to the initial treatment or that reoccurs shortly afterward, Dr. Bishop said.

The standard of care approach for those patients is second-line therapy, he noted, usually with combination chemoimmunotherapy, followed by autologous stem cell transplant if the disease responds to chemotherapy.

“Unfortunately, only a minority of those patients will be found to have chemotherapy-sensitive disease and be able to go on to autologous stem cell transplantation,” Dr. Bishop said. “And even in that subgroup of patients, the outcomes are relatively poor.”

Accordingly, the phase 3 BELINDA study enrolled patients with aggressive non-Hodgkin lymphomas that either did not respond to first-line treatment or that reoccurred within 12 months.

The primary endpoint of the study was EFS, defined as the time from randomization to either stable or progressive disease at or after a week 12 assessment or to any-cause death at any time.

While that primary endpoint was not met for tisa-cel versus standard of care therapy, two other randomized, phase 3 studies presented at the ASH meeting did demonstrate that CAR T-cell therapy extended EFS when given as a second-line lymphoma treatment.

In the randomized, phase 3 ZUMA-7 trial, axicabtagene ciloleucel (axi-cel) significantly improved EFS versus standard of care in the treatment of patients with large B-cell lymphoma refractory to or relapsed within 12 months of adequate first-line therapy, according to investigators.

Similarly, the investigators said that treatment with lisocabtagene maraleucel (liso-cel) led to a significant improvement in EFS in TRANSFORM, a randomized, phase 3 clinical trial that enrolled patients with large B-cell lymphoma that was refractory to first-line therapy or else relapsed within 12 months of that treatment.

“It’s very possible that either or both the patient characteristics and the study design is what led to the difference in the top-line study results,” lymphoma specialist Andrew M. Evens, DO, said in an interview.

There were substantial differences between the studies in terms of what was allowed as optional bridging therapy and salvage therapy, according to Dr. Evens, associate director for clinical services and director of the lymphoma program at Rutgers Cancer Institute in New Brunswick, N.J.

“In ZUMA-7, they only allowed steroids as bridging therapy,” said Dr. Evens, who was not an investigator on any of the three second-line CAR T-cell studies.

In the BELINDA study, optional platinum-based chemotherapy bridging treatment allowed in one arm of the study could have potentially delayed tisa-cel infusion until after the week 6 assessment, study investigators reported in their ASH meeting abstract.

Differences in lymphodepleting therapy prior to CAR T-cell therapy could have also played a role. According to Dr. Bishop, the total doses of cyclophosphamide and fludarabine in BELINDA were 900 mg/m2 and 75 mg/m2, respectively, while in the other two trials, doses were 1,500 mg/m² and 90 mg/m², respectively.

Lymphodepleting chemotherapy is “extremely important” in the success of CAR T-cell therapeutic approaches, he noted at the press conference.

Dr. Bishop reported receiving consultancy fees from Arcellx, Autolus Therapeutics, Bristol-Myers Squibb, CRISPR, Kite/Gilead, and Novartis. He also reported research funding from Bristol-Myers Squibb and Kite/Gilead.