Conference Coverage

WASHINGTON — Microbiota-focused dietary therapy could improve disease outcomes and management of metabolic dysfunction-associated steatotic liver disease (MASLD), according to a study presented at the annual Digestive Disease Week^® (DDW).

For instance, patients with MASLD had lower intake of fiber and omega-3 fatty acids but higher consumption of added sugars and ultraprocessed foods, which correlated with the associated bacterial species and functional pathways.

“MASLD is an escalating concern globally, which highlights the need for innovative targets for disease prevention and management,” said lead author Georgina Williams, PhD, a postdoctoral researcher in diet and gastroenterology at the University of Newcastle, Australia.

“Therapeutic options often rely on lifestyle modifications, with a focus on weight loss,” she said. “Diet is considered a key component of disease management.”

Although calorie restriction with a 3%-5% fat loss is associated with hepatic benefits in MASLD, Dr. Williams noted, researchers have considered whole dietary patterns and the best fit for patients. Aspects of the Mediterranean diet may be effective, as reflected in recommendations from the American Association for the Study of Liver Disease (AASLD), which highlight dietary components such as limited carbohydrates and saturated fat, along with high fiber and unsaturated fats. The gut microbiome may be essential to consider as well, she said, given MASLD-associated differences in bile acid metabolism, inflammation, and ethanol production.

Dr. Williams and colleagues conducted a retrospective case-control study in an outpatient liver clinic to understand diet and dysbiosis in MASLD, looking at differences in diet, gut microbiota composition, and functional pathways in those with and without MASLD. The researchers investigated daily average intake, serum, and stool samples among 50 people (25 per group) matched for age and gender, comparing fibrosis-4, MASLD severity scores, macronutrients, micronutrients, food groups, metagenomic sequencing, and inflammatory markers such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, cytokeratin (CK)-18, and high-sensitivity C-reactive protein (hsCRP).
 

Dietary Characteristics

At baseline, the groups differed by ethnicity, prescription medication use, and body mass index (BMI), where the MASLD group had greater ethnic diversity, medication use, and BMI. In addition, the MASLD group had a zero to mild score of fibrosis.

Overall, energy intake didn’t differ significantly between the two groups. The control group had higher alcohol intake, likely since the MASLD group was recommended to reduce alcohol intake, though the difference was about 5 grams per day. The MASLD group also had less caffeine intake than the control group, as well as slightly lower protein intake, though the differences weren’t statistically significant.

While consumption of total carbohydrates didn’t differ significantly between the groups, participants with MASLD consumed more calories from carbohydrates than did the controls. The MASLD group consumed more calories from added and free sugars and didn’t meet recommendations for dietary fiber.

With particular food groups, participants with MASLD ate significantly fewer whole grains, red and orange fruits, and leafy green vegetables. When consuming fruit, those with MASLD were more likely to drink juice than eat whole fruit. These findings could be relevant when considering high sugar intake and low dietary fiber, Dr. Williams said.

With dietary fat, there were no differences in total fat between the groups, but the fat profiles differed. The control group was significantly more likely to consume omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). The MASLD group was less likely to consume seafood, nuts, seeds, avocado, and olive oil.

With inflammatory markers, hsCRP and CK-18 were increased in MASLD, while IL-1ß was increased in controls, which was consistently associated with higher alcohol intake among the control group. IL-6 and TNF-α didn’t differ between the groups.

Notably, dietary fats were most consistently associated with inflammatory markers, Dr. Williams said, with inflammation being positively associated with saturated fats and negatively associated with unsaturated fats.

Looking at microbiota, the alpha diversity was no different, but the beta diversity was across 162 taxa. Per bacterial species, there was an inverse relationship between MASLD and associations with unsaturated fat, as well as positive indicators of high sugar and fructose intake and low unsaturated fat and dietary fiber intake.

Beyond that, the functional pathways enriched in MASLD were associated with increased sugar and carbohydrates, reduced fiber, and reduced unsaturated fat. Lower butyrate production in MASLD was associated with low intake of nuts, seeds, and unsaturated fat.
 

In Clinical Practice

Dr. Williams suggested reinforcing AASLD guidelines and looking at diet quality, not just diet quantity. Although an energy deficit remains relevant in MASLD, macronutrient consumption matters across dietary fats, fibers, and sugars.

Future avenues for research include metabolomic pathways related to bile acids and fatty acids, she said, as well as disentangling metabolic syndrome from MASLD outcomes.

Session moderator Olivier Barbier, PhD, professor of pharmacy at Laval University in Quebec, Canada, asked about microbiome differences across countries. Dr. Williams noted the limitations in this study of looking at differences across geography and ethnicity, particularly in Australia, but said the species identified were consistent with those found in most literature globally.

In response to other questions after the presentation, Dr. Williams said supplements (such as omega-3 fatty acids) were included in total intake, and those taking prebiotics or probiotics were excluded from the study. In an upcoming clinical trial, she and colleagues plan to control for household microbiomes as well.

“The premise is that microbiomes are shared between households, so when you’re doing these sorts of large-scale clinical studies, if you’re going to look at the microbiome, then you should control for one of the major confounding variables,” said Mark Sundrud, PhD, professor of medicine at the Dartmouth Center for Digestive Health in Lebanon, New Hampshire. Dr. Sundrud, who wasn’t involved with this study, presented on the role of bile acids in mucosal immune cell function at DDW.

“We’ve done a collaborative study looking at microbiomes and bile acids in inflammatory bowel disease (IBD) patients versus controls,” which included consideration of households, he said. “We were able to see more intrinsic disease-specific changes.”

Dr. Williams declared no relevant disclosures. Dr. Sundrud has served as a scientific adviser to Sage Therapeutics.

WASHINGTON — Microbiota-focused dietary therapy could improve disease outcomes and management of metabolic dysfunction-associated steatotic liver disease (MASLD), according to a study presented at the annual Digestive Disease Week^® (DDW).

For instance, patients with MASLD had lower intake of fiber and omega-3 fatty acids but higher consumption of added sugars and ultraprocessed foods, which correlated with the associated bacterial species and functional pathways.

“MASLD is an escalating concern globally, which highlights the need for innovative targets for disease prevention and management,” said lead author Georgina Williams, PhD, a postdoctoral researcher in diet and gastroenterology at the University of Newcastle, Australia.

“Therapeutic options often rely on lifestyle modifications, with a focus on weight loss,” she said. “Diet is considered a key component of disease management.”

Although calorie restriction with a 3%-5% fat loss is associated with hepatic benefits in MASLD, Dr. Williams noted, researchers have considered whole dietary patterns and the best fit for patients. Aspects of the Mediterranean diet may be effective, as reflected in recommendations from the American Association for the Study of Liver Disease (AASLD), which highlight dietary components such as limited carbohydrates and saturated fat, along with high fiber and unsaturated fats. The gut microbiome may be essential to consider as well, she said, given MASLD-associated differences in bile acid metabolism, inflammation, and ethanol production.

Dr. Williams and colleagues conducted a retrospective case-control study in an outpatient liver clinic to understand diet and dysbiosis in MASLD, looking at differences in diet, gut microbiota composition, and functional pathways in those with and without MASLD. The researchers investigated daily average intake, serum, and stool samples among 50 people (25 per group) matched for age and gender, comparing fibrosis-4, MASLD severity scores, macronutrients, micronutrients, food groups, metagenomic sequencing, and inflammatory markers such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, cytokeratin (CK)-18, and high-sensitivity C-reactive protein (hsCRP).
 

Dietary Characteristics

At baseline, the groups differed by ethnicity, prescription medication use, and body mass index (BMI), where the MASLD group had greater ethnic diversity, medication use, and BMI. In addition, the MASLD group had a zero to mild score of fibrosis.

Overall, energy intake didn’t differ significantly between the two groups. The control group had higher alcohol intake, likely since the MASLD group was recommended to reduce alcohol intake, though the difference was about 5 grams per day. The MASLD group also had less caffeine intake than the control group, as well as slightly lower protein intake, though the differences weren’t statistically significant.

While consumption of total carbohydrates didn’t differ significantly between the groups, participants with MASLD consumed more calories from carbohydrates than did the controls. The MASLD group consumed more calories from added and free sugars and didn’t meet recommendations for dietary fiber.

With particular food groups, participants with MASLD ate significantly fewer whole grains, red and orange fruits, and leafy green vegetables. When consuming fruit, those with MASLD were more likely to drink juice than eat whole fruit. These findings could be relevant when considering high sugar intake and low dietary fiber, Dr. Williams said.

With dietary fat, there were no differences in total fat between the groups, but the fat profiles differed. The control group was significantly more likely to consume omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). The MASLD group was less likely to consume seafood, nuts, seeds, avocado, and olive oil.

With inflammatory markers, hsCRP and CK-18 were increased in MASLD, while IL-1ß was increased in controls, which was consistently associated with higher alcohol intake among the control group. IL-6 and TNF-α didn’t differ between the groups.

Notably, dietary fats were most consistently associated with inflammatory markers, Dr. Williams said, with inflammation being positively associated with saturated fats and negatively associated with unsaturated fats.

Looking at microbiota, the alpha diversity was no different, but the beta diversity was across 162 taxa. Per bacterial species, there was an inverse relationship between MASLD and associations with unsaturated fat, as well as positive indicators of high sugar and fructose intake and low unsaturated fat and dietary fiber intake.

Beyond that, the functional pathways enriched in MASLD were associated with increased sugar and carbohydrates, reduced fiber, and reduced unsaturated fat. Lower butyrate production in MASLD was associated with low intake of nuts, seeds, and unsaturated fat.
 

In Clinical Practice

Dr. Williams suggested reinforcing AASLD guidelines and looking at diet quality, not just diet quantity. Although an energy deficit remains relevant in MASLD, macronutrient consumption matters across dietary fats, fibers, and sugars.

Future avenues for research include metabolomic pathways related to bile acids and fatty acids, she said, as well as disentangling metabolic syndrome from MASLD outcomes.

Session moderator Olivier Barbier, PhD, professor of pharmacy at Laval University in Quebec, Canada, asked about microbiome differences across countries. Dr. Williams noted the limitations in this study of looking at differences across geography and ethnicity, particularly in Australia, but said the species identified were consistent with those found in most literature globally.

In response to other questions after the presentation, Dr. Williams said supplements (such as omega-3 fatty acids) were included in total intake, and those taking prebiotics or probiotics were excluded from the study. In an upcoming clinical trial, she and colleagues plan to control for household microbiomes as well.

“The premise is that microbiomes are shared between households, so when you’re doing these sorts of large-scale clinical studies, if you’re going to look at the microbiome, then you should control for one of the major confounding variables,” said Mark Sundrud, PhD, professor of medicine at the Dartmouth Center for Digestive Health in Lebanon, New Hampshire. Dr. Sundrud, who wasn’t involved with this study, presented on the role of bile acids in mucosal immune cell function at DDW.

“We’ve done a collaborative study looking at microbiomes and bile acids in inflammatory bowel disease (IBD) patients versus controls,” which included consideration of households, he said. “We were able to see more intrinsic disease-specific changes.”

Dr. Williams declared no relevant disclosures. Dr. Sundrud has served as a scientific adviser to Sage Therapeutics.

WASHINGTON — Microbiota-focused dietary therapy could improve disease outcomes and management of metabolic dysfunction-associated steatotic liver disease (MASLD), according to a study presented at the annual Digestive Disease Week^® (DDW).

For instance, patients with MASLD had lower intake of fiber and omega-3 fatty acids but higher consumption of added sugars and ultraprocessed foods, which correlated with the associated bacterial species and functional pathways.

“MASLD is an escalating concern globally, which highlights the need for innovative targets for disease prevention and management,” said lead author Georgina Williams, PhD, a postdoctoral researcher in diet and gastroenterology at the University of Newcastle, Australia.

“Therapeutic options often rely on lifestyle modifications, with a focus on weight loss,” she said. “Diet is considered a key component of disease management.”

Although calorie restriction with a 3%-5% fat loss is associated with hepatic benefits in MASLD, Dr. Williams noted, researchers have considered whole dietary patterns and the best fit for patients. Aspects of the Mediterranean diet may be effective, as reflected in recommendations from the American Association for the Study of Liver Disease (AASLD), which highlight dietary components such as limited carbohydrates and saturated fat, along with high fiber and unsaturated fats. The gut microbiome may be essential to consider as well, she said, given MASLD-associated differences in bile acid metabolism, inflammation, and ethanol production.

Dr. Williams and colleagues conducted a retrospective case-control study in an outpatient liver clinic to understand diet and dysbiosis in MASLD, looking at differences in diet, gut microbiota composition, and functional pathways in those with and without MASLD. The researchers investigated daily average intake, serum, and stool samples among 50 people (25 per group) matched for age and gender, comparing fibrosis-4, MASLD severity scores, macronutrients, micronutrients, food groups, metagenomic sequencing, and inflammatory markers such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, cytokeratin (CK)-18, and high-sensitivity C-reactive protein (hsCRP).
 

Dietary Characteristics

At baseline, the groups differed by ethnicity, prescription medication use, and body mass index (BMI), where the MASLD group had greater ethnic diversity, medication use, and BMI. In addition, the MASLD group had a zero to mild score of fibrosis.

Overall, energy intake didn’t differ significantly between the two groups. The control group had higher alcohol intake, likely since the MASLD group was recommended to reduce alcohol intake, though the difference was about 5 grams per day. The MASLD group also had less caffeine intake than the control group, as well as slightly lower protein intake, though the differences weren’t statistically significant.

While consumption of total carbohydrates didn’t differ significantly between the groups, participants with MASLD consumed more calories from carbohydrates than did the controls. The MASLD group consumed more calories from added and free sugars and didn’t meet recommendations for dietary fiber.

With particular food groups, participants with MASLD ate significantly fewer whole grains, red and orange fruits, and leafy green vegetables. When consuming fruit, those with MASLD were more likely to drink juice than eat whole fruit. These findings could be relevant when considering high sugar intake and low dietary fiber, Dr. Williams said.

With dietary fat, there were no differences in total fat between the groups, but the fat profiles differed. The control group was significantly more likely to consume omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). The MASLD group was less likely to consume seafood, nuts, seeds, avocado, and olive oil.

With inflammatory markers, hsCRP and CK-18 were increased in MASLD, while IL-1ß was increased in controls, which was consistently associated with higher alcohol intake among the control group. IL-6 and TNF-α didn’t differ between the groups.

Notably, dietary fats were most consistently associated with inflammatory markers, Dr. Williams said, with inflammation being positively associated with saturated fats and negatively associated with unsaturated fats.

Looking at microbiota, the alpha diversity was no different, but the beta diversity was across 162 taxa. Per bacterial species, there was an inverse relationship between MASLD and associations with unsaturated fat, as well as positive indicators of high sugar and fructose intake and low unsaturated fat and dietary fiber intake.

Beyond that, the functional pathways enriched in MASLD were associated with increased sugar and carbohydrates, reduced fiber, and reduced unsaturated fat. Lower butyrate production in MASLD was associated with low intake of nuts, seeds, and unsaturated fat.
 

In Clinical Practice

Dr. Williams suggested reinforcing AASLD guidelines and looking at diet quality, not just diet quantity. Although an energy deficit remains relevant in MASLD, macronutrient consumption matters across dietary fats, fibers, and sugars.

Future avenues for research include metabolomic pathways related to bile acids and fatty acids, she said, as well as disentangling metabolic syndrome from MASLD outcomes.

Session moderator Olivier Barbier, PhD, professor of pharmacy at Laval University in Quebec, Canada, asked about microbiome differences across countries. Dr. Williams noted the limitations in this study of looking at differences across geography and ethnicity, particularly in Australia, but said the species identified were consistent with those found in most literature globally.

In response to other questions after the presentation, Dr. Williams said supplements (such as omega-3 fatty acids) were included in total intake, and those taking prebiotics or probiotics were excluded from the study. In an upcoming clinical trial, she and colleagues plan to control for household microbiomes as well.

“The premise is that microbiomes are shared between households, so when you’re doing these sorts of large-scale clinical studies, if you’re going to look at the microbiome, then you should control for one of the major confounding variables,” said Mark Sundrud, PhD, professor of medicine at the Dartmouth Center for Digestive Health in Lebanon, New Hampshire. Dr. Sundrud, who wasn’t involved with this study, presented on the role of bile acids in mucosal immune cell function at DDW.

“We’ve done a collaborative study looking at microbiomes and bile acids in inflammatory bowel disease (IBD) patients versus controls,” which included consideration of households, he said. “We were able to see more intrinsic disease-specific changes.”

Dr. Williams declared no relevant disclosures. Dr. Sundrud has served as a scientific adviser to Sage Therapeutics.

Over a period of 5 years, the likelihood of major adverse cardiovascular events (MACE) in patients with psoriasis and dyslipidemia who were on statin therapy was 40% greater than that in non-psoriasis patients with dyslipidemia on statin therapy, even after adjusting for covariates, results from a large retrospective study showed.

“It is well-established that psoriasis is an independent risk factor for the development of MACE, with cardiometabolic risk factors being more prevalent and incident among patients with psoriasis,” the study’s first author Ana Ormaza Vera, MD, a dermatology research fellow at Eastern Virginia Medical School, Norfolk, said in an interview after the annual meeting of the Society for Investigational Dermatology, where the study was presented during a late-breaking abstract session.

Dr. Ormaza Vera

Current guidelines from the joint American Academy of Dermatology/National Psoriasis Foundation and the American Academy of Cardiology/American Heart Association Task Force recommend statins, a lipid-lowering and anti-inflammatory therapy, “for patients with psoriasis who have additional risk-enhancing factors, similar to recommendations made for the general population without psoriasis,” she noted. But how the incidence of MACE differs between patients with and without psoriasis while on statin therapy “has not been explored in real-world settings,” she added.

To address this question, the researchers used real-world data from the TriNetX health research network to identify individuals aged 18-90 years with a diagnosis of both psoriasis and lipid disorders who were undergoing treatment with statins. Those with a prior history of MACE were excluded from the analysis. Patients with lipid disorders on statin therapy, but without psoriatic disease, were matched 1:1 by age, sex, race, ethnicity, common risk factors for MACE, and medications shown to reduce MACE risk. The researchers then assessed the cohorts 5 years following their first statin prescription and used the TriNetX analytics tool to calculate the odds ratio (OR) with 95% CI to evaluate the likelihood of MACE in the presence of statin therapy.

Dr. Ormaza Vera and colleagues identified 20,660 patients with psoriasis and 2,768,429 patients without psoriasis who met the criteria for analysis. After propensity score matching, each cohort included 20,660 patients with a mean age of 60 years. During the 5-year observation period, 2725 patients in the psoriasis cohort experienced MACE compared with 2203 patients in the non-psoriasis cohort (OR, 1.40; 95% CI, 1.317-1.488).

“This was an unexpected outcome that challenges the current understanding and highlights the need for further research into tailored treatments for cardiovascular risk in psoriasis patients,” Dr. Ormaza Vera told this news organization.

She acknowledged certain limitations of the study, including its retrospective design, the inherent limitations of an observational study, and the use of electronic medical record data.

Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, who was asked to comment on the study results, said that the findings imply that there is more than statin use alone to protect someone with psoriasis from having an increased risk for MACE. “This is not really surprising because statin use alone is only part of a prevention strategy in someone with psoriasis who usually has multiple comorbidities,” Dr. Green said. “On the other hand, the study only went out for 5 years and cardiovascular disease is a long accumulating process, so it could also be too early to demonstrate MACE prevention.”

The study was funded by a grant from the American Skin Association. Dr. Ormaza Vera and her coauthors reported having no relevant disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies.

A version of this article appeared on Medscape.com .

Over a period of 5 years, the likelihood of major adverse cardiovascular events (MACE) in patients with psoriasis and dyslipidemia who were on statin therapy was 40% greater than that in non-psoriasis patients with dyslipidemia on statin therapy, even after adjusting for covariates, results from a large retrospective study showed.

“It is well-established that psoriasis is an independent risk factor for the development of MACE, with cardiometabolic risk factors being more prevalent and incident among patients with psoriasis,” the study’s first author Ana Ormaza Vera, MD, a dermatology research fellow at Eastern Virginia Medical School, Norfolk, said in an interview after the annual meeting of the Society for Investigational Dermatology, where the study was presented during a late-breaking abstract session.

Dr. Ormaza Vera

Current guidelines from the joint American Academy of Dermatology/National Psoriasis Foundation and the American Academy of Cardiology/American Heart Association Task Force recommend statins, a lipid-lowering and anti-inflammatory therapy, “for patients with psoriasis who have additional risk-enhancing factors, similar to recommendations made for the general population without psoriasis,” she noted. But how the incidence of MACE differs between patients with and without psoriasis while on statin therapy “has not been explored in real-world settings,” she added.

To address this question, the researchers used real-world data from the TriNetX health research network to identify individuals aged 18-90 years with a diagnosis of both psoriasis and lipid disorders who were undergoing treatment with statins. Those with a prior history of MACE were excluded from the analysis. Patients with lipid disorders on statin therapy, but without psoriatic disease, were matched 1:1 by age, sex, race, ethnicity, common risk factors for MACE, and medications shown to reduce MACE risk. The researchers then assessed the cohorts 5 years following their first statin prescription and used the TriNetX analytics tool to calculate the odds ratio (OR) with 95% CI to evaluate the likelihood of MACE in the presence of statin therapy.

Dr. Ormaza Vera and colleagues identified 20,660 patients with psoriasis and 2,768,429 patients without psoriasis who met the criteria for analysis. After propensity score matching, each cohort included 20,660 patients with a mean age of 60 years. During the 5-year observation period, 2725 patients in the psoriasis cohort experienced MACE compared with 2203 patients in the non-psoriasis cohort (OR, 1.40; 95% CI, 1.317-1.488).

“This was an unexpected outcome that challenges the current understanding and highlights the need for further research into tailored treatments for cardiovascular risk in psoriasis patients,” Dr. Ormaza Vera told this news organization.

She acknowledged certain limitations of the study, including its retrospective design, the inherent limitations of an observational study, and the use of electronic medical record data.

Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, who was asked to comment on the study results, said that the findings imply that there is more than statin use alone to protect someone with psoriasis from having an increased risk for MACE. “This is not really surprising because statin use alone is only part of a prevention strategy in someone with psoriasis who usually has multiple comorbidities,” Dr. Green said. “On the other hand, the study only went out for 5 years and cardiovascular disease is a long accumulating process, so it could also be too early to demonstrate MACE prevention.”

The study was funded by a grant from the American Skin Association. Dr. Ormaza Vera and her coauthors reported having no relevant disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies.

A version of this article appeared on Medscape.com .

Over a period of 5 years, the likelihood of major adverse cardiovascular events (MACE) in patients with psoriasis and dyslipidemia who were on statin therapy was 40% greater than that in non-psoriasis patients with dyslipidemia on statin therapy, even after adjusting for covariates, results from a large retrospective study showed.

“It is well-established that psoriasis is an independent risk factor for the development of MACE, with cardiometabolic risk factors being more prevalent and incident among patients with psoriasis,” the study’s first author Ana Ormaza Vera, MD, a dermatology research fellow at Eastern Virginia Medical School, Norfolk, said in an interview after the annual meeting of the Society for Investigational Dermatology, where the study was presented during a late-breaking abstract session.

Dr. Ormaza Vera

Current guidelines from the joint American Academy of Dermatology/National Psoriasis Foundation and the American Academy of Cardiology/American Heart Association Task Force recommend statins, a lipid-lowering and anti-inflammatory therapy, “for patients with psoriasis who have additional risk-enhancing factors, similar to recommendations made for the general population without psoriasis,” she noted. But how the incidence of MACE differs between patients with and without psoriasis while on statin therapy “has not been explored in real-world settings,” she added.

To address this question, the researchers used real-world data from the TriNetX health research network to identify individuals aged 18-90 years with a diagnosis of both psoriasis and lipid disorders who were undergoing treatment with statins. Those with a prior history of MACE were excluded from the analysis. Patients with lipid disorders on statin therapy, but without psoriatic disease, were matched 1:1 by age, sex, race, ethnicity, common risk factors for MACE, and medications shown to reduce MACE risk. The researchers then assessed the cohorts 5 years following their first statin prescription and used the TriNetX analytics tool to calculate the odds ratio (OR) with 95% CI to evaluate the likelihood of MACE in the presence of statin therapy.

Dr. Ormaza Vera and colleagues identified 20,660 patients with psoriasis and 2,768,429 patients without psoriasis who met the criteria for analysis. After propensity score matching, each cohort included 20,660 patients with a mean age of 60 years. During the 5-year observation period, 2725 patients in the psoriasis cohort experienced MACE compared with 2203 patients in the non-psoriasis cohort (OR, 1.40; 95% CI, 1.317-1.488).

“This was an unexpected outcome that challenges the current understanding and highlights the need for further research into tailored treatments for cardiovascular risk in psoriasis patients,” Dr. Ormaza Vera told this news organization.

She acknowledged certain limitations of the study, including its retrospective design, the inherent limitations of an observational study, and the use of electronic medical record data.

Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, who was asked to comment on the study results, said that the findings imply that there is more than statin use alone to protect someone with psoriasis from having an increased risk for MACE. “This is not really surprising because statin use alone is only part of a prevention strategy in someone with psoriasis who usually has multiple comorbidities,” Dr. Green said. “On the other hand, the study only went out for 5 years and cardiovascular disease is a long accumulating process, so it could also be too early to demonstrate MACE prevention.”

The study was funded by a grant from the American Skin Association. Dr. Ormaza Vera and her coauthors reported having no relevant disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies.

A version of this article appeared on Medscape.com .

More than 40% of patients with inflammatory bowel disease (IBD) screened positive for joint pain symptomatic of spondyloarthritis (SpA), according to a new study.

Of these patients, 75% did not have any history of arthritis.

“What we know is that a substantial proportion of patients with IBD do report musculoskeletal symptoms, and inflammatory back pain stands out as being one of the more frequent symptoms reported,” said Reem Jan, MBBS, a rheumatologist at the University of Chicago Medicine. She presented the study findings during the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN) in Cleveland.

“Yet a minority of these patients are evaluated by rheumatologists. So that suggests there’s a high burden of need in the IBD population to have this joint pain evaluated and addressed,” she said during her presentation.

She presented preliminary data from an ongoing project to better understand the prevalence of inflammatory arthritis in IBD — estimates range from 17% to 39%— and the risk factors for developing arthritis in this patient population.
 

Study Details

Researchers enrolled patients from outpatient gastroenterology clinics or procedure units at NYU Langone Health, New York City; Brigham and Women’s Hospital, Boston; University of Colorado Anschutz Medical Campus, Aurora, Colorado; Mayo Clinic, Rochester, Minnesota; University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago; and Icahn School of Medicine at Mount Sinai, New York City. Additional patients were recruited from Mercy Health, a community health system in Ohio.

Upon entry into the study, participants completed a survey documenting their history with joint pain. The survey combined questions from the DETAIL and the IBIS questionnaires.

Between January 2021 and December 2022, 669 patients joined the study. In total, 41% of patients (n = 275) screened positive.

“What really stood out to us was that of all the positive screens, only about a quarter of those patients were known to have SpA,” Dr. Jan said during her presentation. “[This] means 75% of the patients who screened positive were not known to have any type of arthritic disease.”

In addition, only 24% (n = 65) of all patients who screened positive — including those with a SpA diagnosis — had seen a rheumatologist in the previous year.

Among these patients, inflammatory back pain was the most commonly reported symptom, followed by painful swelling of peripheral joints and heel pain.

Excluding patients with a SpA diagnosis, researchers also investigated which characteristics were associated with a higher likelihood of screening positive in the questionnaire. The analysis, including 588 patients, identified the following risk factors:

• Female sex: Odds ratio (OR), 2.0; 95% CI, 1.4-2.9
• Older age: OR, 1.02; 95% CI, 1.01-1.4
• History of smoking: OR, 1.7; 95% CI, 1.1-2.6
• History of prior IBD-related surgery: OR, 1.60; 95% CI, 1.1-2.5
• History of biologic or small molecule therapy: OR, 2.3; 95% CI, 1.4-4.0

Future Directions

Commenting on the study, Mark Hwang, MD, a rheumatologist at UTHealth Houston, noted that it was “very interesting to see the fairly large, positive rates” of joint pain in patients with IBD, which certainly have clinical implications. However, it is not yet known if any of these patients went on to be diagnosed with SpA.

Jan noted that potential next steps include a follow-up analysis of patients who screened positive to see how many went on to see a rheumatologist and which patients were ultimately diagnosed with SpA or other inflammatory arthritis conditions.

These findings are a first step, Dr. Hwang said, and will likely “help further establish some of the validity of these questionnaires by testing in different patient populations,” he noted.

The ultimate goal is to “develop really good strategies to risk stratify IBD patients with the greatest need of rheumatologist consultation,” Dr. Jan said. “We certainly don’t want to see all these patients, so how can we figure out who really needs to be seen?”

Funding information was not available for this study. Dr. Hwang is conducting two clinical trials for psoriatic arthritis sponsored by Janssen and Eli Lilly. Dr. Jan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

More than 40% of patients with inflammatory bowel disease (IBD) screened positive for joint pain symptomatic of spondyloarthritis (SpA), according to a new study.

Of these patients, 75% did not have any history of arthritis.

“What we know is that a substantial proportion of patients with IBD do report musculoskeletal symptoms, and inflammatory back pain stands out as being one of the more frequent symptoms reported,” said Reem Jan, MBBS, a rheumatologist at the University of Chicago Medicine. She presented the study findings during the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN) in Cleveland.

“Yet a minority of these patients are evaluated by rheumatologists. So that suggests there’s a high burden of need in the IBD population to have this joint pain evaluated and addressed,” she said during her presentation.

She presented preliminary data from an ongoing project to better understand the prevalence of inflammatory arthritis in IBD — estimates range from 17% to 39%— and the risk factors for developing arthritis in this patient population.
 

Study Details

Researchers enrolled patients from outpatient gastroenterology clinics or procedure units at NYU Langone Health, New York City; Brigham and Women’s Hospital, Boston; University of Colorado Anschutz Medical Campus, Aurora, Colorado; Mayo Clinic, Rochester, Minnesota; University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago; and Icahn School of Medicine at Mount Sinai, New York City. Additional patients were recruited from Mercy Health, a community health system in Ohio.

Upon entry into the study, participants completed a survey documenting their history with joint pain. The survey combined questions from the DETAIL and the IBIS questionnaires.

Between January 2021 and December 2022, 669 patients joined the study. In total, 41% of patients (n = 275) screened positive.

“What really stood out to us was that of all the positive screens, only about a quarter of those patients were known to have SpA,” Dr. Jan said during her presentation. “[This] means 75% of the patients who screened positive were not known to have any type of arthritic disease.”

In addition, only 24% (n = 65) of all patients who screened positive — including those with a SpA diagnosis — had seen a rheumatologist in the previous year.

Among these patients, inflammatory back pain was the most commonly reported symptom, followed by painful swelling of peripheral joints and heel pain.

Excluding patients with a SpA diagnosis, researchers also investigated which characteristics were associated with a higher likelihood of screening positive in the questionnaire. The analysis, including 588 patients, identified the following risk factors:

• Female sex: Odds ratio (OR), 2.0; 95% CI, 1.4-2.9
• Older age: OR, 1.02; 95% CI, 1.01-1.4
• History of smoking: OR, 1.7; 95% CI, 1.1-2.6
• History of prior IBD-related surgery: OR, 1.60; 95% CI, 1.1-2.5
• History of biologic or small molecule therapy: OR, 2.3; 95% CI, 1.4-4.0

Future Directions

Commenting on the study, Mark Hwang, MD, a rheumatologist at UTHealth Houston, noted that it was “very interesting to see the fairly large, positive rates” of joint pain in patients with IBD, which certainly have clinical implications. However, it is not yet known if any of these patients went on to be diagnosed with SpA.

Jan noted that potential next steps include a follow-up analysis of patients who screened positive to see how many went on to see a rheumatologist and which patients were ultimately diagnosed with SpA or other inflammatory arthritis conditions.

These findings are a first step, Dr. Hwang said, and will likely “help further establish some of the validity of these questionnaires by testing in different patient populations,” he noted.

The ultimate goal is to “develop really good strategies to risk stratify IBD patients with the greatest need of rheumatologist consultation,” Dr. Jan said. “We certainly don’t want to see all these patients, so how can we figure out who really needs to be seen?”

Funding information was not available for this study. Dr. Hwang is conducting two clinical trials for psoriatic arthritis sponsored by Janssen and Eli Lilly. Dr. Jan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

More than 40% of patients with inflammatory bowel disease (IBD) screened positive for joint pain symptomatic of spondyloarthritis (SpA), according to a new study.

Of these patients, 75% did not have any history of arthritis.

“What we know is that a substantial proportion of patients with IBD do report musculoskeletal symptoms, and inflammatory back pain stands out as being one of the more frequent symptoms reported,” said Reem Jan, MBBS, a rheumatologist at the University of Chicago Medicine. She presented the study findings during the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN) in Cleveland.

“Yet a minority of these patients are evaluated by rheumatologists. So that suggests there’s a high burden of need in the IBD population to have this joint pain evaluated and addressed,” she said during her presentation.

She presented preliminary data from an ongoing project to better understand the prevalence of inflammatory arthritis in IBD — estimates range from 17% to 39%— and the risk factors for developing arthritis in this patient population.
 

Study Details

Researchers enrolled patients from outpatient gastroenterology clinics or procedure units at NYU Langone Health, New York City; Brigham and Women’s Hospital, Boston; University of Colorado Anschutz Medical Campus, Aurora, Colorado; Mayo Clinic, Rochester, Minnesota; University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago; and Icahn School of Medicine at Mount Sinai, New York City. Additional patients were recruited from Mercy Health, a community health system in Ohio.

Upon entry into the study, participants completed a survey documenting their history with joint pain. The survey combined questions from the DETAIL and the IBIS questionnaires.

Between January 2021 and December 2022, 669 patients joined the study. In total, 41% of patients (n = 275) screened positive.

“What really stood out to us was that of all the positive screens, only about a quarter of those patients were known to have SpA,” Dr. Jan said during her presentation. “[This] means 75% of the patients who screened positive were not known to have any type of arthritic disease.”

In addition, only 24% (n = 65) of all patients who screened positive — including those with a SpA diagnosis — had seen a rheumatologist in the previous year.

Among these patients, inflammatory back pain was the most commonly reported symptom, followed by painful swelling of peripheral joints and heel pain.

Excluding patients with a SpA diagnosis, researchers also investigated which characteristics were associated with a higher likelihood of screening positive in the questionnaire. The analysis, including 588 patients, identified the following risk factors:

• Female sex: Odds ratio (OR), 2.0; 95% CI, 1.4-2.9
• Older age: OR, 1.02; 95% CI, 1.01-1.4
• History of smoking: OR, 1.7; 95% CI, 1.1-2.6
• History of prior IBD-related surgery: OR, 1.60; 95% CI, 1.1-2.5
• History of biologic or small molecule therapy: OR, 2.3; 95% CI, 1.4-4.0

Future Directions

Commenting on the study, Mark Hwang, MD, a rheumatologist at UTHealth Houston, noted that it was “very interesting to see the fairly large, positive rates” of joint pain in patients with IBD, which certainly have clinical implications. However, it is not yet known if any of these patients went on to be diagnosed with SpA.

Jan noted that potential next steps include a follow-up analysis of patients who screened positive to see how many went on to see a rheumatologist and which patients were ultimately diagnosed with SpA or other inflammatory arthritis conditions.

These findings are a first step, Dr. Hwang said, and will likely “help further establish some of the validity of these questionnaires by testing in different patient populations,” he noted.

The ultimate goal is to “develop really good strategies to risk stratify IBD patients with the greatest need of rheumatologist consultation,” Dr. Jan said. “We certainly don’t want to see all these patients, so how can we figure out who really needs to be seen?”

Funding information was not available for this study. Dr. Hwang is conducting two clinical trials for psoriatic arthritis sponsored by Janssen and Eli Lilly. Dr. Jan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

NASHVILLE, TENNESSEE — Among people with MS who have mild symptoms, non-motor symptoms like dizziness, fatigue, and spasticity predict later perception of balance, walking, and physical quality of life. However, these associations fall away among patients with more severe disease, according to a new study performed in Australia. The findings could eventually help tailor physical activity interventions.

The research grew out of frustrations with developing interventions focused on strength. “There are many systematic reviews showing stronger and stronger evidence that exercise is beneficial. It does change your walking. It does improve your balance,” said Katrina Williams, PhD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.

However, when her group’s intervention studies yielded no statistically significant improvements, she began to search for explanations, and began to suspect heterogeneity among MS patients. Their clinic took all comers, regardless of disability level. “[Our attitude was] we will make it work. We’ll get you actively moving and exercising. But when you break down a lot of those systematic reviews, there’s not a lot of teasing out of disability levels. So, potentially, it is the disability level that might be leading to why some people don’t change or why we’re not getting the statistically significant benefits, because we’re not addressing the individual at their level of disease progression,” said Dr. Williams, who is a senior lecturer in physiotherapy at the University of Queensland, Brisbane, Australia.

“Physiotherapists, we love exercise, we love movement, but we’re a bit unidimensional. It’s some strength training, [or] let’s get on that bike and do cardiovascular. But that may not be enough for individuals who have different symptoms profiles. We’re assuming that the motor profile is the most important, and the one that needs to be addressed in these individuals,” said Dr. Williams.
 

Focusing on Non-Motor Symptoms

When she searched the literature, she could find little evidence of non-motor symptoms correlating to walking, balance, or even quality of life. To dig deeper, her group studied 220 MS patients in Australia who self-reported symptoms of dizziness, vision problems, fatigue, and spasticity. The population had a mean age of 42 years, and 82% were female. They ranged in disease severity from disease step (DS) 0 to DS 6. The researchers categorized respondents as between DS 0 (mild symptoms that were mostly sensory) to DS 3 (MS interferes with walking) and from DS 4 (early cane use) to DS 6 (requiring bilateral walking support).

Deficits were more commonly reported in the DS 4-6 group than the DS 0-3 group with respect to light touch (88% vs 72%), proprioception (63% vs 41%), fatigue (100% vs 96%), and spasticity (78% vs 69%). There were no significant differences in dizziness, vision, or memory/cognition/emotion.

A linear regression model incorporating sensory worsening, age, social participation, perceived deficit, and spasticity showed an R² adjusted value of 0.73. However, when they looked only at DS 0-3 patients, the R² value strengthened to 0.86. Among the DS 4-6 group, the correlation largely disappeared with an R² value of 0.16. Specifically, there were stronger associations in the DS 0-3 group than the overall group (DS 0-6) between perceived walking deficit and sensory worsening (R² 0.45 vs 0.31), fatigue (0.67 vs 0.05), spasticity (0.47 vs 0.16), and balance (0.8 vs 0.16).

“Most non-motor symptoms do have moderate to weak correlations to walking confidence and walking balance, and quality of life, and the correlations do decline as disability worsens. Those with less disability had more correlations that were stronger, particularly for the walking and balance confidence. So [among those] walking without an aid, there are more non-motor correlations aligned to the actual outcomes. In more disabled, they fell away, so there’s something else going on that we do have to look at,” said Dr. Williams.

She called for other clinicians to explore non-motor symptoms in patients with less disability, and the relationships of those symptoms to gait, balance, and overall MS impact, in the hopes that such observations could improve the tailoring of physiotherapy programs.
 

Perception May Differ From Actual Function

During the Q&A session, Nora Fritz, PhD, an associate professor of neurology at Wayne State University, Detroit, Michigan, asked about the lack of correlations seen in more disabled patients. “It’s not exactly what you would expect to happen,” said Dr. Fritz, in an interview.

She asked Dr. Williams if the study had sufficient power to detect associations in patients with more severe disability, since the study had a relatively small sample size and many predictors in its regression model. Dr. Fritz also noted that perceptions may differ from actual function, so actual function can’t be captured using a survey. Dr. Williams responded that the group is now working to incorporate more clinical measures to their correlations.

Another audience member said she was “perplexed” by the drop-off of correlation in the most severe group. She suggested the possibility that as patients become more disabled, they may be less likely to perceive the relatively less severe non-motor symptoms and therefore did not report them.

Dr. Williams and Dr. Fritz have no relevant financial disclosures.

NASHVILLE, TENNESSEE — Among people with MS who have mild symptoms, non-motor symptoms like dizziness, fatigue, and spasticity predict later perception of balance, walking, and physical quality of life. However, these associations fall away among patients with more severe disease, according to a new study performed in Australia. The findings could eventually help tailor physical activity interventions.

The research grew out of frustrations with developing interventions focused on strength. “There are many systematic reviews showing stronger and stronger evidence that exercise is beneficial. It does change your walking. It does improve your balance,” said Katrina Williams, PhD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.

However, when her group’s intervention studies yielded no statistically significant improvements, she began to search for explanations, and began to suspect heterogeneity among MS patients. Their clinic took all comers, regardless of disability level. “[Our attitude was] we will make it work. We’ll get you actively moving and exercising. But when you break down a lot of those systematic reviews, there’s not a lot of teasing out of disability levels. So, potentially, it is the disability level that might be leading to why some people don’t change or why we’re not getting the statistically significant benefits, because we’re not addressing the individual at their level of disease progression,” said Dr. Williams, who is a senior lecturer in physiotherapy at the University of Queensland, Brisbane, Australia.

“Physiotherapists, we love exercise, we love movement, but we’re a bit unidimensional. It’s some strength training, [or] let’s get on that bike and do cardiovascular. But that may not be enough for individuals who have different symptoms profiles. We’re assuming that the motor profile is the most important, and the one that needs to be addressed in these individuals,” said Dr. Williams.
 

Focusing on Non-Motor Symptoms

When she searched the literature, she could find little evidence of non-motor symptoms correlating to walking, balance, or even quality of life. To dig deeper, her group studied 220 MS patients in Australia who self-reported symptoms of dizziness, vision problems, fatigue, and spasticity. The population had a mean age of 42 years, and 82% were female. They ranged in disease severity from disease step (DS) 0 to DS 6. The researchers categorized respondents as between DS 0 (mild symptoms that were mostly sensory) to DS 3 (MS interferes with walking) and from DS 4 (early cane use) to DS 6 (requiring bilateral walking support).

Deficits were more commonly reported in the DS 4-6 group than the DS 0-3 group with respect to light touch (88% vs 72%), proprioception (63% vs 41%), fatigue (100% vs 96%), and spasticity (78% vs 69%). There were no significant differences in dizziness, vision, or memory/cognition/emotion.

A linear regression model incorporating sensory worsening, age, social participation, perceived deficit, and spasticity showed an R² adjusted value of 0.73. However, when they looked only at DS 0-3 patients, the R² value strengthened to 0.86. Among the DS 4-6 group, the correlation largely disappeared with an R² value of 0.16. Specifically, there were stronger associations in the DS 0-3 group than the overall group (DS 0-6) between perceived walking deficit and sensory worsening (R² 0.45 vs 0.31), fatigue (0.67 vs 0.05), spasticity (0.47 vs 0.16), and balance (0.8 vs 0.16).

“Most non-motor symptoms do have moderate to weak correlations to walking confidence and walking balance, and quality of life, and the correlations do decline as disability worsens. Those with less disability had more correlations that were stronger, particularly for the walking and balance confidence. So [among those] walking without an aid, there are more non-motor correlations aligned to the actual outcomes. In more disabled, they fell away, so there’s something else going on that we do have to look at,” said Dr. Williams.

She called for other clinicians to explore non-motor symptoms in patients with less disability, and the relationships of those symptoms to gait, balance, and overall MS impact, in the hopes that such observations could improve the tailoring of physiotherapy programs.
 

Perception May Differ From Actual Function

During the Q&A session, Nora Fritz, PhD, an associate professor of neurology at Wayne State University, Detroit, Michigan, asked about the lack of correlations seen in more disabled patients. “It’s not exactly what you would expect to happen,” said Dr. Fritz, in an interview.

She asked Dr. Williams if the study had sufficient power to detect associations in patients with more severe disability, since the study had a relatively small sample size and many predictors in its regression model. Dr. Fritz also noted that perceptions may differ from actual function, so actual function can’t be captured using a survey. Dr. Williams responded that the group is now working to incorporate more clinical measures to their correlations.

Another audience member said she was “perplexed” by the drop-off of correlation in the most severe group. She suggested the possibility that as patients become more disabled, they may be less likely to perceive the relatively less severe non-motor symptoms and therefore did not report them.

Dr. Williams and Dr. Fritz have no relevant financial disclosures.

NASHVILLE, TENNESSEE — Among people with MS who have mild symptoms, non-motor symptoms like dizziness, fatigue, and spasticity predict later perception of balance, walking, and physical quality of life. However, these associations fall away among patients with more severe disease, according to a new study performed in Australia. The findings could eventually help tailor physical activity interventions.

The research grew out of frustrations with developing interventions focused on strength. “There are many systematic reviews showing stronger and stronger evidence that exercise is beneficial. It does change your walking. It does improve your balance,” said Katrina Williams, PhD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.

However, when her group’s intervention studies yielded no statistically significant improvements, she began to search for explanations, and began to suspect heterogeneity among MS patients. Their clinic took all comers, regardless of disability level. “[Our attitude was] we will make it work. We’ll get you actively moving and exercising. But when you break down a lot of those systematic reviews, there’s not a lot of teasing out of disability levels. So, potentially, it is the disability level that might be leading to why some people don’t change or why we’re not getting the statistically significant benefits, because we’re not addressing the individual at their level of disease progression,” said Dr. Williams, who is a senior lecturer in physiotherapy at the University of Queensland, Brisbane, Australia.

“Physiotherapists, we love exercise, we love movement, but we’re a bit unidimensional. It’s some strength training, [or] let’s get on that bike and do cardiovascular. But that may not be enough for individuals who have different symptoms profiles. We’re assuming that the motor profile is the most important, and the one that needs to be addressed in these individuals,” said Dr. Williams.
 

Focusing on Non-Motor Symptoms

When she searched the literature, she could find little evidence of non-motor symptoms correlating to walking, balance, or even quality of life. To dig deeper, her group studied 220 MS patients in Australia who self-reported symptoms of dizziness, vision problems, fatigue, and spasticity. The population had a mean age of 42 years, and 82% were female. They ranged in disease severity from disease step (DS) 0 to DS 6. The researchers categorized respondents as between DS 0 (mild symptoms that were mostly sensory) to DS 3 (MS interferes with walking) and from DS 4 (early cane use) to DS 6 (requiring bilateral walking support).

Deficits were more commonly reported in the DS 4-6 group than the DS 0-3 group with respect to light touch (88% vs 72%), proprioception (63% vs 41%), fatigue (100% vs 96%), and spasticity (78% vs 69%). There were no significant differences in dizziness, vision, or memory/cognition/emotion.

A linear regression model incorporating sensory worsening, age, social participation, perceived deficit, and spasticity showed an R² adjusted value of 0.73. However, when they looked only at DS 0-3 patients, the R² value strengthened to 0.86. Among the DS 4-6 group, the correlation largely disappeared with an R² value of 0.16. Specifically, there were stronger associations in the DS 0-3 group than the overall group (DS 0-6) between perceived walking deficit and sensory worsening (R² 0.45 vs 0.31), fatigue (0.67 vs 0.05), spasticity (0.47 vs 0.16), and balance (0.8 vs 0.16).

“Most non-motor symptoms do have moderate to weak correlations to walking confidence and walking balance, and quality of life, and the correlations do decline as disability worsens. Those with less disability had more correlations that were stronger, particularly for the walking and balance confidence. So [among those] walking without an aid, there are more non-motor correlations aligned to the actual outcomes. In more disabled, they fell away, so there’s something else going on that we do have to look at,” said Dr. Williams.

She called for other clinicians to explore non-motor symptoms in patients with less disability, and the relationships of those symptoms to gait, balance, and overall MS impact, in the hopes that such observations could improve the tailoring of physiotherapy programs.
 

Perception May Differ From Actual Function

During the Q&A session, Nora Fritz, PhD, an associate professor of neurology at Wayne State University, Detroit, Michigan, asked about the lack of correlations seen in more disabled patients. “It’s not exactly what you would expect to happen,” said Dr. Fritz, in an interview.

She asked Dr. Williams if the study had sufficient power to detect associations in patients with more severe disability, since the study had a relatively small sample size and many predictors in its regression model. Dr. Fritz also noted that perceptions may differ from actual function, so actual function can’t be captured using a survey. Dr. Williams responded that the group is now working to incorporate more clinical measures to their correlations.

Another audience member said she was “perplexed” by the drop-off of correlation in the most severe group. She suggested the possibility that as patients become more disabled, they may be less likely to perceive the relatively less severe non-motor symptoms and therefore did not report them.

Dr. Williams and Dr. Fritz have no relevant financial disclosures.

Children with concomitant atopic dermatitis (AD) and alopecia areata (AA) who were treated with dupilumab demonstrated significant hair regrowth over a mean of nearly 68 weeks, preliminary results from a small case series showed.

“We might be opening a new avenue for a safe, long-term treatment for our children with AA,” the study’s lead investigator, Emma Guttman-Yassky, MD, PhD, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York City, said in an interview during the annual meeting of the Society for Investigative Dermatology (SID), where the results were presented during a poster session. “I think AA is likely joining the atopic march, which may allow us to adapt some treatments from the atopy world to AA.”

When the original phase 2 and phase 3 trials of dupilumab for patients with moderate to severe AD were being conducted, Dr. Guttman-Yassky, one of the investigators, recalled observing that some patients who also had patch alopecia experienced hair regrowth. “I was scratching my head because, at the time, AA was considered to be only a Th1-driven disease,” she said. “I asked myself, ‘How can this happen?’ I looked in the literature and found many publications linking atopy in general to alopecia areata. The largest of the dermatologic publications showed that eczema and atopy in general are the highest comorbidities in alopecia areata.”

Courtesy Mount Sinai Health System

“This and other findings such as IL [interleukin]-13 genetic linkage with AA and high IgE in patients with AA link AA with Th2 immune skewing, particularly in the setting of atopy,” she continued. In addition, she said, in a large biomarker study involving the scalp and blood of patients with AA, “we found increases in Th2 biomarkers that were associated with alopecia severity.”
 

Case Series of 20 Pediatric Patients

As part of a case series of children with both AD and AA, Dr. Guttman-Yassky and colleagues evaluated hair regrowth using the Severity of Alopecia Tool (SALT) in 20 pediatric patients (mean age, 10.8 years) who were being treated at Mount Sinai. They collected patient demographics, atopic history, immunoglobulin E (IgE) levels, and SALT scores at follow-up visits every 12-16 weeks for more than 72 weeks and performed Spearman correlations between clinical scores, demographics, and IgE levels.

At baseline, the mean SALT score was 54.4, the mean IgE level was 1567.7 IU/mL, and 75% of patients also had a family history of atopy. The mean follow-up was 67.6 weeks. The researchers observed a significant reduction in SALT scores at week 48 compared with baseline (a mean score of 20.4; P < .01) and continued improvement up to at least 72 weeks (P < .01 vs baseline). They also noted that patients who achieved a treatment response at week 24 had baseline IgE levels > 200 IU/mL.

In other findings, baseline IgE positively correlated with improvement in SALT scores at week 36 (P < .05), while baseline SALT scores positively correlated with disease duration (P < .01) and negatively correlated with improvement in SALT scores at weeks 24, 36, and 48 (P < .005). “The robustness of the response surprised me,” Dr. Guttman-Yassky said in the interview. “Dupilumab for AA takes time to work, but once it kicks in, it kicks in. It takes anywhere from 6 to 12 months to see hair regrowth.”

She acknowledged certain limitations of the analysis, including its small sample size and the fact that it was not a standardized trial. “But, based on our data and the adult data, we are very encouraged about the potential of using dupilumab for children with AA,” she said.

Mount Sinai recently announced that the National Institutes of Health awarded a $6.6 million, 5-year grant to Dr. Guttman-Yassky to further investigate dupilumab as a treatment for children with AA. She will lead a multicenter controlled trial of 76 children with alopecia affecting at least 30% of the scalp, who will be randomized 2:1 (dupilumab:placebo) for 48 weeks, followed by 48 weeks of open-label dupilumab for all participants, with 16 weeks of follow-up, for a total of 112 weeks. Participating sites include Mount Sinai, Yale University, Northwestern University, and the University of California, Irvine.

Dr. Guttman-Yassky disclosed that she is a consultant to many pharmaceutical companies, including dupilumab manufacturers Sanofi and Regeneron.

A version of this article appeared on Medscape.com.

Children with concomitant atopic dermatitis (AD) and alopecia areata (AA) who were treated with dupilumab demonstrated significant hair regrowth over a mean of nearly 68 weeks, preliminary results from a small case series showed.

“We might be opening a new avenue for a safe, long-term treatment for our children with AA,” the study’s lead investigator, Emma Guttman-Yassky, MD, PhD, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York City, said in an interview during the annual meeting of the Society for Investigative Dermatology (SID), where the results were presented during a poster session. “I think AA is likely joining the atopic march, which may allow us to adapt some treatments from the atopy world to AA.”

When the original phase 2 and phase 3 trials of dupilumab for patients with moderate to severe AD were being conducted, Dr. Guttman-Yassky, one of the investigators, recalled observing that some patients who also had patch alopecia experienced hair regrowth. “I was scratching my head because, at the time, AA was considered to be only a Th1-driven disease,” she said. “I asked myself, ‘How can this happen?’ I looked in the literature and found many publications linking atopy in general to alopecia areata. The largest of the dermatologic publications showed that eczema and atopy in general are the highest comorbidities in alopecia areata.”

Courtesy Mount Sinai Health System

“This and other findings such as IL [interleukin]-13 genetic linkage with AA and high IgE in patients with AA link AA with Th2 immune skewing, particularly in the setting of atopy,” she continued. In addition, she said, in a large biomarker study involving the scalp and blood of patients with AA, “we found increases in Th2 biomarkers that were associated with alopecia severity.”
 

Case Series of 20 Pediatric Patients

As part of a case series of children with both AD and AA, Dr. Guttman-Yassky and colleagues evaluated hair regrowth using the Severity of Alopecia Tool (SALT) in 20 pediatric patients (mean age, 10.8 years) who were being treated at Mount Sinai. They collected patient demographics, atopic history, immunoglobulin E (IgE) levels, and SALT scores at follow-up visits every 12-16 weeks for more than 72 weeks and performed Spearman correlations between clinical scores, demographics, and IgE levels.

At baseline, the mean SALT score was 54.4, the mean IgE level was 1567.7 IU/mL, and 75% of patients also had a family history of atopy. The mean follow-up was 67.6 weeks. The researchers observed a significant reduction in SALT scores at week 48 compared with baseline (a mean score of 20.4; P < .01) and continued improvement up to at least 72 weeks (P < .01 vs baseline). They also noted that patients who achieved a treatment response at week 24 had baseline IgE levels > 200 IU/mL.

In other findings, baseline IgE positively correlated with improvement in SALT scores at week 36 (P < .05), while baseline SALT scores positively correlated with disease duration (P < .01) and negatively correlated with improvement in SALT scores at weeks 24, 36, and 48 (P < .005). “The robustness of the response surprised me,” Dr. Guttman-Yassky said in the interview. “Dupilumab for AA takes time to work, but once it kicks in, it kicks in. It takes anywhere from 6 to 12 months to see hair regrowth.”

She acknowledged certain limitations of the analysis, including its small sample size and the fact that it was not a standardized trial. “But, based on our data and the adult data, we are very encouraged about the potential of using dupilumab for children with AA,” she said.

Mount Sinai recently announced that the National Institutes of Health awarded a $6.6 million, 5-year grant to Dr. Guttman-Yassky to further investigate dupilumab as a treatment for children with AA. She will lead a multicenter controlled trial of 76 children with alopecia affecting at least 30% of the scalp, who will be randomized 2:1 (dupilumab:placebo) for 48 weeks, followed by 48 weeks of open-label dupilumab for all participants, with 16 weeks of follow-up, for a total of 112 weeks. Participating sites include Mount Sinai, Yale University, Northwestern University, and the University of California, Irvine.

Dr. Guttman-Yassky disclosed that she is a consultant to many pharmaceutical companies, including dupilumab manufacturers Sanofi and Regeneron.

A version of this article appeared on Medscape.com.

Children with concomitant atopic dermatitis (AD) and alopecia areata (AA) who were treated with dupilumab demonstrated significant hair regrowth over a mean of nearly 68 weeks, preliminary results from a small case series showed.

“We might be opening a new avenue for a safe, long-term treatment for our children with AA,” the study’s lead investigator, Emma Guttman-Yassky, MD, PhD, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York City, said in an interview during the annual meeting of the Society for Investigative Dermatology (SID), where the results were presented during a poster session. “I think AA is likely joining the atopic march, which may allow us to adapt some treatments from the atopy world to AA.”

When the original phase 2 and phase 3 trials of dupilumab for patients with moderate to severe AD were being conducted, Dr. Guttman-Yassky, one of the investigators, recalled observing that some patients who also had patch alopecia experienced hair regrowth. “I was scratching my head because, at the time, AA was considered to be only a Th1-driven disease,” she said. “I asked myself, ‘How can this happen?’ I looked in the literature and found many publications linking atopy in general to alopecia areata. The largest of the dermatologic publications showed that eczema and atopy in general are the highest comorbidities in alopecia areata.”

Courtesy Mount Sinai Health System

“This and other findings such as IL [interleukin]-13 genetic linkage with AA and high IgE in patients with AA link AA with Th2 immune skewing, particularly in the setting of atopy,” she continued. In addition, she said, in a large biomarker study involving the scalp and blood of patients with AA, “we found increases in Th2 biomarkers that were associated with alopecia severity.”
 

Case Series of 20 Pediatric Patients

As part of a case series of children with both AD and AA, Dr. Guttman-Yassky and colleagues evaluated hair regrowth using the Severity of Alopecia Tool (SALT) in 20 pediatric patients (mean age, 10.8 years) who were being treated at Mount Sinai. They collected patient demographics, atopic history, immunoglobulin E (IgE) levels, and SALT scores at follow-up visits every 12-16 weeks for more than 72 weeks and performed Spearman correlations between clinical scores, demographics, and IgE levels.

At baseline, the mean SALT score was 54.4, the mean IgE level was 1567.7 IU/mL, and 75% of patients also had a family history of atopy. The mean follow-up was 67.6 weeks. The researchers observed a significant reduction in SALT scores at week 48 compared with baseline (a mean score of 20.4; P < .01) and continued improvement up to at least 72 weeks (P < .01 vs baseline). They also noted that patients who achieved a treatment response at week 24 had baseline IgE levels > 200 IU/mL.

In other findings, baseline IgE positively correlated with improvement in SALT scores at week 36 (P < .05), while baseline SALT scores positively correlated with disease duration (P < .01) and negatively correlated with improvement in SALT scores at weeks 24, 36, and 48 (P < .005). “The robustness of the response surprised me,” Dr. Guttman-Yassky said in the interview. “Dupilumab for AA takes time to work, but once it kicks in, it kicks in. It takes anywhere from 6 to 12 months to see hair regrowth.”

She acknowledged certain limitations of the analysis, including its small sample size and the fact that it was not a standardized trial. “But, based on our data and the adult data, we are very encouraged about the potential of using dupilumab for children with AA,” she said.

Mount Sinai recently announced that the National Institutes of Health awarded a $6.6 million, 5-year grant to Dr. Guttman-Yassky to further investigate dupilumab as a treatment for children with AA. She will lead a multicenter controlled trial of 76 children with alopecia affecting at least 30% of the scalp, who will be randomized 2:1 (dupilumab:placebo) for 48 weeks, followed by 48 weeks of open-label dupilumab for all participants, with 16 weeks of follow-up, for a total of 112 weeks. Participating sites include Mount Sinai, Yale University, Northwestern University, and the University of California, Irvine.

Dr. Guttman-Yassky disclosed that she is a consultant to many pharmaceutical companies, including dupilumab manufacturers Sanofi and Regeneron.

A version of this article appeared on Medscape.com.

Almost sixty percent of patients with macroscopic stage III melanoma who were randomized to 6 weeks of neoadjuvant immunotherapy needed no further treatment after therapeutic lymph node dissection in the phase 3 NADINA trial.

These results set a new standard of care in this patient population, the study’s lead author, Christian U. Blank, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Blank, a hematologist/oncologist from the Netherlands Cancer Institute in Amsterdam, called the result “very special,” noting that the trial included an active comparator, rather than a placebo control.

“When we treat these patients with surgery only, the outcome … is very bad: The 5-year relapse-free survival is only 30% and the overall survival is only 50%. Adjuvant therapy improves relapse-free survival but not overall survival ...Thus, there is an urgent need for these patients for novel therapy approaches,” he said during a press conference at the meeting.
 

Study Methods and Results

The study included 423 patients with stage III de novo or recurrent pathologically proven resectable melanoma with at least 1 lymph node metastasis. Patients were randomized to either the experimental neoadjuvant arm (n = 212), or the standard treatment control arm (n = 211), which consisted of therapeutic lymph node dissection (TLND) followed by 12 cycles of adjuvant nivolumab (NIVO 480 mg every 4 weeks).

Patients in the experimental arm received two cycles of neoadjuvant ipilimumab (IPI 80 mg every 3 weeks) plus NIVO 240 mg for 3 weeks followed by TLND. Those with a major pathologic response (MPR), defined as less than 10% vital tumor cells in the post-neoadjuvant resection specimen, went straight to follow-up.

Those without an MPR received adjuvant therapy. For patients with BRAF wild-type, this involved 11 cycles of adjuvant NIVO (480 mg every 4 weeks), while BRAF-mutated patients received dabrafenib plus trametinib (150 mg b.i.d./2 mg once a day; 46 weeks).

The study met its primary endpoint — event-free survival (EFS) — at the first interim analysis. After a median follow-up of 9.9 months, the estimated EFS was 83.7% for neoadjuvant immunotherapy versus 57.2% for standard of care, (P less than .0001, hazard ratio [HR] = 0.32).

“When we look into the subgroups, for example BRAF-mutated status or BRAF-wild-type status ... you see for both groups also a highly statistically significant outcome favoring the neoadjuvant therapy with hazard ratios of 0.29 and 0.35,” said Dr. Blank.

In total, 59% of patients in the experimental arm had an MPR needing no further treatment. “This is important, because the patients that achieve a major pathologic response have excellent outcomes, with an EFS of 95%,” said Dr. Blank.

He added that those with a partial response had an EFS of 76%, and among those who had “nonresponse,” the EFS was 57% — the same as that of patients in the control arm.

Toxicities were considered transient and acceptable, with systemic treatment-related grade 3 or 4 events in 29.7% of the neoadjuvant arm and 14.7% of the adjuvant arm.

NADINA is the first neoadjuvant checkpoint inhibitor phase 3 study in melanoma and the first phase 3 trial in oncology testing a checkpoint inhibitor without chemotherapy, noted Dr. Blank.

“At the moment we see only additions of immunotherapy to the chemotherapy neoadjuvant arms, but here you see that we can also treat patients with pure immunotherapy.”
 

Neoadjuvant Therapy Defined as Standard of Care

When considered along with evidence from the phase 2 SWOG 1801 study (N Engl J Med. 2023;388:813-8), “NADINA defines neoadjuvant therapy as the new standard of care for macroscopic stage III melanoma “which means that all trials currently ongoing need to be amended from adjuvant comparators to neoadjuvant comparators,” he said.

Dr. Blank called the trial a “new template for other malignancies implementing a neoadjuvant immunotherapy regimen followed by a response-driven adjuvant therapy.

“I think we see at the moment only sandwich designs, and this is more sales driven than patient driven, because what we have seen is that if a patient achieves a really deep response, the patient doesn’t need an adjuvant part,” he said.

Commenting during the press conference, Michael Lowe, MD, said the result “confirms and shows for the first time in a phase 3 study that giving immunotherapy before surgery results in superior outcomes to giving immunotherapy only after surgery.”

Dr. Lowe, associate professor in the Division of Surgical Oncology, at Emory University School of Medicine, Atlanta, added that the study “also confirms that giving two immunotherapy drugs before surgery results in excellent responses.”

However, he cautioned that “we cannot make comparisons to trials in which patients only got one immunotherapy. But this study confirms that consistency that patients who receive ipilimumab and nivolumab have superior responses compared to single-agent immunotherapy.”

He noted that all of the patients in the new study had all of their lymph nodes removed and called for doing that to remain the standard of care in terms of surgical approach.

“With short follow-up, it is too early to tell if some patients may have benefited from that adjuvant therapy. However, NADINA confirms that immunotherapy should be given to all patients with advanced melanoma before surgery, when possible, and establishes dual therapy with nivolumab and ipilimumab, as the standard of care in the appropriate patient,” Dr. Lowe said.
 

EFS Improvement Exceeds Expectations

In an interview, Rodabe N. Amaria, MD, a medical oncologist and professor at The University of Texas MD Anderson Cancer Center in Houston, agreed with Dr. Lowe’s assessment of the findings.

“For years we have been doing neoadjuvant immunotherapy trials, all with favorable results, but all relatively small, with data that was intriguing, but not necessarily definitive,” she said. “I see the data from the NADINA trial as being definitive and true evidence of the many advantages of neoadjuvant immunotherapy for clinical stage 3 melanoma ... This work builds on the data from the SWOG 1801 trial but also exceeds expectations with the 68% improvement in EFS appreciated with the dual combination immunotherapy regimen compared to adjuvant nivolumab.”

Additionally, the approximately 30% grade 3 or higher immune-mediated toxicity is reasonable and in keeping with known data, and this trial demonstrates clearly that neoadjuvant immunotherapy does not increase the rate of surgical complications, she said.

Dr. Amaria also considered that 59% of patients who achieved a major pathologic response were observed in the neoadjuvant setting to be a key finding.

This indicates thats “over half the patients could be spared additional immunotherapy and risk of further immune-mediated toxicities by having only two doses of neoadjuvant immunotherapy, she said.

The results “demonstrate the superiority of a neoadjuvant combination immunotherapy approach for patients with clinical stage III melanoma,” she added.

The study was funded by Bristol Myers-Squibb and the Australian government.

Dr. Blank disclosed ties with Immagene, Signature Oncology, AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Third Rock Ventures, 4SC, NanoString Technologies, WO 2021/177822 A1, and Freshfields Bruckhaus Deringer. No other experts reported any relevant disclosures.

Almost sixty percent of patients with macroscopic stage III melanoma who were randomized to 6 weeks of neoadjuvant immunotherapy needed no further treatment after therapeutic lymph node dissection in the phase 3 NADINA trial.

These results set a new standard of care in this patient population, the study’s lead author, Christian U. Blank, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Blank, a hematologist/oncologist from the Netherlands Cancer Institute in Amsterdam, called the result “very special,” noting that the trial included an active comparator, rather than a placebo control.

“When we treat these patients with surgery only, the outcome … is very bad: The 5-year relapse-free survival is only 30% and the overall survival is only 50%. Adjuvant therapy improves relapse-free survival but not overall survival ...Thus, there is an urgent need for these patients for novel therapy approaches,” he said during a press conference at the meeting.
 

Study Methods and Results

The study included 423 patients with stage III de novo or recurrent pathologically proven resectable melanoma with at least 1 lymph node metastasis. Patients were randomized to either the experimental neoadjuvant arm (n = 212), or the standard treatment control arm (n = 211), which consisted of therapeutic lymph node dissection (TLND) followed by 12 cycles of adjuvant nivolumab (NIVO 480 mg every 4 weeks).

Patients in the experimental arm received two cycles of neoadjuvant ipilimumab (IPI 80 mg every 3 weeks) plus NIVO 240 mg for 3 weeks followed by TLND. Those with a major pathologic response (MPR), defined as less than 10% vital tumor cells in the post-neoadjuvant resection specimen, went straight to follow-up.

Those without an MPR received adjuvant therapy. For patients with BRAF wild-type, this involved 11 cycles of adjuvant NIVO (480 mg every 4 weeks), while BRAF-mutated patients received dabrafenib plus trametinib (150 mg b.i.d./2 mg once a day; 46 weeks).

The study met its primary endpoint — event-free survival (EFS) — at the first interim analysis. After a median follow-up of 9.9 months, the estimated EFS was 83.7% for neoadjuvant immunotherapy versus 57.2% for standard of care, (P less than .0001, hazard ratio [HR] = 0.32).

“When we look into the subgroups, for example BRAF-mutated status or BRAF-wild-type status ... you see for both groups also a highly statistically significant outcome favoring the neoadjuvant therapy with hazard ratios of 0.29 and 0.35,” said Dr. Blank.

In total, 59% of patients in the experimental arm had an MPR needing no further treatment. “This is important, because the patients that achieve a major pathologic response have excellent outcomes, with an EFS of 95%,” said Dr. Blank.

He added that those with a partial response had an EFS of 76%, and among those who had “nonresponse,” the EFS was 57% — the same as that of patients in the control arm.

Toxicities were considered transient and acceptable, with systemic treatment-related grade 3 or 4 events in 29.7% of the neoadjuvant arm and 14.7% of the adjuvant arm.

NADINA is the first neoadjuvant checkpoint inhibitor phase 3 study in melanoma and the first phase 3 trial in oncology testing a checkpoint inhibitor without chemotherapy, noted Dr. Blank.

“At the moment we see only additions of immunotherapy to the chemotherapy neoadjuvant arms, but here you see that we can also treat patients with pure immunotherapy.”
 

Neoadjuvant Therapy Defined as Standard of Care

When considered along with evidence from the phase 2 SWOG 1801 study (N Engl J Med. 2023;388:813-8), “NADINA defines neoadjuvant therapy as the new standard of care for macroscopic stage III melanoma “which means that all trials currently ongoing need to be amended from adjuvant comparators to neoadjuvant comparators,” he said.

Dr. Blank called the trial a “new template for other malignancies implementing a neoadjuvant immunotherapy regimen followed by a response-driven adjuvant therapy.

“I think we see at the moment only sandwich designs, and this is more sales driven than patient driven, because what we have seen is that if a patient achieves a really deep response, the patient doesn’t need an adjuvant part,” he said.

Commenting during the press conference, Michael Lowe, MD, said the result “confirms and shows for the first time in a phase 3 study that giving immunotherapy before surgery results in superior outcomes to giving immunotherapy only after surgery.”

Dr. Lowe, associate professor in the Division of Surgical Oncology, at Emory University School of Medicine, Atlanta, added that the study “also confirms that giving two immunotherapy drugs before surgery results in excellent responses.”

However, he cautioned that “we cannot make comparisons to trials in which patients only got one immunotherapy. But this study confirms that consistency that patients who receive ipilimumab and nivolumab have superior responses compared to single-agent immunotherapy.”

He noted that all of the patients in the new study had all of their lymph nodes removed and called for doing that to remain the standard of care in terms of surgical approach.

“With short follow-up, it is too early to tell if some patients may have benefited from that adjuvant therapy. However, NADINA confirms that immunotherapy should be given to all patients with advanced melanoma before surgery, when possible, and establishes dual therapy with nivolumab and ipilimumab, as the standard of care in the appropriate patient,” Dr. Lowe said.
 

EFS Improvement Exceeds Expectations

In an interview, Rodabe N. Amaria, MD, a medical oncologist and professor at The University of Texas MD Anderson Cancer Center in Houston, agreed with Dr. Lowe’s assessment of the findings.

“For years we have been doing neoadjuvant immunotherapy trials, all with favorable results, but all relatively small, with data that was intriguing, but not necessarily definitive,” she said. “I see the data from the NADINA trial as being definitive and true evidence of the many advantages of neoadjuvant immunotherapy for clinical stage 3 melanoma ... This work builds on the data from the SWOG 1801 trial but also exceeds expectations with the 68% improvement in EFS appreciated with the dual combination immunotherapy regimen compared to adjuvant nivolumab.”

Additionally, the approximately 30% grade 3 or higher immune-mediated toxicity is reasonable and in keeping with known data, and this trial demonstrates clearly that neoadjuvant immunotherapy does not increase the rate of surgical complications, she said.

Dr. Amaria also considered that 59% of patients who achieved a major pathologic response were observed in the neoadjuvant setting to be a key finding.

This indicates thats “over half the patients could be spared additional immunotherapy and risk of further immune-mediated toxicities by having only two doses of neoadjuvant immunotherapy, she said.

The results “demonstrate the superiority of a neoadjuvant combination immunotherapy approach for patients with clinical stage III melanoma,” she added.

The study was funded by Bristol Myers-Squibb and the Australian government.

Dr. Blank disclosed ties with Immagene, Signature Oncology, AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Third Rock Ventures, 4SC, NanoString Technologies, WO 2021/177822 A1, and Freshfields Bruckhaus Deringer. No other experts reported any relevant disclosures.

Almost sixty percent of patients with macroscopic stage III melanoma who were randomized to 6 weeks of neoadjuvant immunotherapy needed no further treatment after therapeutic lymph node dissection in the phase 3 NADINA trial.

These results set a new standard of care in this patient population, the study’s lead author, Christian U. Blank, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Blank, a hematologist/oncologist from the Netherlands Cancer Institute in Amsterdam, called the result “very special,” noting that the trial included an active comparator, rather than a placebo control.

“When we treat these patients with surgery only, the outcome … is very bad: The 5-year relapse-free survival is only 30% and the overall survival is only 50%. Adjuvant therapy improves relapse-free survival but not overall survival ...Thus, there is an urgent need for these patients for novel therapy approaches,” he said during a press conference at the meeting.
 

Study Methods and Results

The study included 423 patients with stage III de novo or recurrent pathologically proven resectable melanoma with at least 1 lymph node metastasis. Patients were randomized to either the experimental neoadjuvant arm (n = 212), or the standard treatment control arm (n = 211), which consisted of therapeutic lymph node dissection (TLND) followed by 12 cycles of adjuvant nivolumab (NIVO 480 mg every 4 weeks).

Patients in the experimental arm received two cycles of neoadjuvant ipilimumab (IPI 80 mg every 3 weeks) plus NIVO 240 mg for 3 weeks followed by TLND. Those with a major pathologic response (MPR), defined as less than 10% vital tumor cells in the post-neoadjuvant resection specimen, went straight to follow-up.

Those without an MPR received adjuvant therapy. For patients with BRAF wild-type, this involved 11 cycles of adjuvant NIVO (480 mg every 4 weeks), while BRAF-mutated patients received dabrafenib plus trametinib (150 mg b.i.d./2 mg once a day; 46 weeks).

The study met its primary endpoint — event-free survival (EFS) — at the first interim analysis. After a median follow-up of 9.9 months, the estimated EFS was 83.7% for neoadjuvant immunotherapy versus 57.2% for standard of care, (P less than .0001, hazard ratio [HR] = 0.32).

“When we look into the subgroups, for example BRAF-mutated status or BRAF-wild-type status ... you see for both groups also a highly statistically significant outcome favoring the neoadjuvant therapy with hazard ratios of 0.29 and 0.35,” said Dr. Blank.

In total, 59% of patients in the experimental arm had an MPR needing no further treatment. “This is important, because the patients that achieve a major pathologic response have excellent outcomes, with an EFS of 95%,” said Dr. Blank.

He added that those with a partial response had an EFS of 76%, and among those who had “nonresponse,” the EFS was 57% — the same as that of patients in the control arm.

Toxicities were considered transient and acceptable, with systemic treatment-related grade 3 or 4 events in 29.7% of the neoadjuvant arm and 14.7% of the adjuvant arm.

NADINA is the first neoadjuvant checkpoint inhibitor phase 3 study in melanoma and the first phase 3 trial in oncology testing a checkpoint inhibitor without chemotherapy, noted Dr. Blank.

“At the moment we see only additions of immunotherapy to the chemotherapy neoadjuvant arms, but here you see that we can also treat patients with pure immunotherapy.”
 

Neoadjuvant Therapy Defined as Standard of Care

When considered along with evidence from the phase 2 SWOG 1801 study (N Engl J Med. 2023;388:813-8), “NADINA defines neoadjuvant therapy as the new standard of care for macroscopic stage III melanoma “which means that all trials currently ongoing need to be amended from adjuvant comparators to neoadjuvant comparators,” he said.

Dr. Blank called the trial a “new template for other malignancies implementing a neoadjuvant immunotherapy regimen followed by a response-driven adjuvant therapy.

“I think we see at the moment only sandwich designs, and this is more sales driven than patient driven, because what we have seen is that if a patient achieves a really deep response, the patient doesn’t need an adjuvant part,” he said.

Commenting during the press conference, Michael Lowe, MD, said the result “confirms and shows for the first time in a phase 3 study that giving immunotherapy before surgery results in superior outcomes to giving immunotherapy only after surgery.”

Dr. Lowe, associate professor in the Division of Surgical Oncology, at Emory University School of Medicine, Atlanta, added that the study “also confirms that giving two immunotherapy drugs before surgery results in excellent responses.”

However, he cautioned that “we cannot make comparisons to trials in which patients only got one immunotherapy. But this study confirms that consistency that patients who receive ipilimumab and nivolumab have superior responses compared to single-agent immunotherapy.”

He noted that all of the patients in the new study had all of their lymph nodes removed and called for doing that to remain the standard of care in terms of surgical approach.

“With short follow-up, it is too early to tell if some patients may have benefited from that adjuvant therapy. However, NADINA confirms that immunotherapy should be given to all patients with advanced melanoma before surgery, when possible, and establishes dual therapy with nivolumab and ipilimumab, as the standard of care in the appropriate patient,” Dr. Lowe said.
 

EFS Improvement Exceeds Expectations

In an interview, Rodabe N. Amaria, MD, a medical oncologist and professor at The University of Texas MD Anderson Cancer Center in Houston, agreed with Dr. Lowe’s assessment of the findings.

“For years we have been doing neoadjuvant immunotherapy trials, all with favorable results, but all relatively small, with data that was intriguing, but not necessarily definitive,” she said. “I see the data from the NADINA trial as being definitive and true evidence of the many advantages of neoadjuvant immunotherapy for clinical stage 3 melanoma ... This work builds on the data from the SWOG 1801 trial but also exceeds expectations with the 68% improvement in EFS appreciated with the dual combination immunotherapy regimen compared to adjuvant nivolumab.”

Additionally, the approximately 30% grade 3 or higher immune-mediated toxicity is reasonable and in keeping with known data, and this trial demonstrates clearly that neoadjuvant immunotherapy does not increase the rate of surgical complications, she said.

Dr. Amaria also considered that 59% of patients who achieved a major pathologic response were observed in the neoadjuvant setting to be a key finding.

This indicates thats “over half the patients could be spared additional immunotherapy and risk of further immune-mediated toxicities by having only two doses of neoadjuvant immunotherapy, she said.

The results “demonstrate the superiority of a neoadjuvant combination immunotherapy approach for patients with clinical stage III melanoma,” she added.

The study was funded by Bristol Myers-Squibb and the Australian government.

Dr. Blank disclosed ties with Immagene, Signature Oncology, AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Third Rock Ventures, 4SC, NanoString Technologies, WO 2021/177822 A1, and Freshfields Bruckhaus Deringer. No other experts reported any relevant disclosures.

BASEL, SWITZERLAND — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.

“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.

The results were presented at the European Stroke Organization Conference (ESOC) 2024.

Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.

Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.

The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.

Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.

Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.

The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.

Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.

Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.

In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
 

A Novel Target for Stroke Treatment

In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.

In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).

“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.

He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.

“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.

Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.

“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.

“I think we have a new tool, but of course we need further trials to confirm that,” she added.

The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.

“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.

The results were presented at the European Stroke Organization Conference (ESOC) 2024.

Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.

Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.

The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.

Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.

Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.

The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.

Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.

Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.

In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
 

A Novel Target for Stroke Treatment

In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.

In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).

“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.

He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.

“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.

Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.

“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.

“I think we have a new tool, but of course we need further trials to confirm that,” she added.

The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.

“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.

The results were presented at the European Stroke Organization Conference (ESOC) 2024.

Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.

Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.

The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.

Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.

Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.

The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.

Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.

Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.

In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
 

A Novel Target for Stroke Treatment

In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.

In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).

“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.

He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.

“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.

Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.

“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.

“I think we have a new tool, but of course we need further trials to confirm that,” she added.

The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Routine removal of healthy lymph nodes should not be a part of ovarian cancer treatment, according to results of the CARACO trial.

Retroperitoneal pelvic and para-aortic lymphadenectomy (RPPL) in patients undergoing either primary or interval surgery during ovarian cancer treatment for advanced epithelial ovarian cancer (AEOC) resulted in no benefit and significant harm, the new study found.

“[RPPL] brings only toxicity and it does not increase survival ... because we have a lot of improvement with other treatments than surgery,” lead author Jean-Marc Classe, MD, PhD, said during a press conference at the annual meeting of the American Society of Clinical Oncology. “It’s a surgical de-escalation, because it is not useful.”

Enrollment for the multicenter, phase III CARACO trial stagnated after the LION trial (N Engl J Med . 2019 Feb 28;380[9]:822-832) showed no benefit to doing RPPL in patients undergoing primary surgery for AEOC. Ultimately, the CARACO trial did not enroll the prespecified sample size needed in order for the researchers to show that not doing RPPL was superior. 

Dr. Classe, a surgical oncologist at Nantes Université, in Nantes, France, explained that primary surgery is currently much less common than interval surgery for AEOC , thus it was important to design the CARACO trial to explore the risks and benefits of RPPL in a patient population that included more interval surgery.

CARACO enrolled 379 patients, with median age 64-65 years, and was closed prematurely due to stagnation of enrollment. Patients were randomized to no-RPPL (n = 193) or RPPL (n = 186), with about 75% in each arm receiving interval surgery (neoadjuvant chemotherapy, followed by cytoreductive surgery and adjuvant chemotherapy), and about 25% receiving primary surgery (initial cytoreductive surgery followed by adjuvant chemotherapy). There was a similar postsurgical rate of no residual disease (85.6% and 88.3% in the no-RPPL and RPPL groups, respectively), and lymph node metastases were diagnosed in 43% of the patients in the RPPL arm, with a median of 3 involved lymph nodes.

After a median follow-up of 9 years both the primary endpoint of progression-free survival (PFS), and secondary endpoint of overall survival (OS) showed no advantage to RPPL, with a median PFS of 14.8 months in the no-RPPL arm and 18.5 months in the RPPL arm (HR 0.96), and a median OS of 48.9 months and 58.0 months respectively (HR 0.92).

Surgery in the lymphadenectomy arm was 300 minutes versus 240 minutes.

“We observed statistically significant more morbidity in the lymphadenectomy arm with more transfusion (72 vs 57 patients), more re-intervention (15 vs 6 patients), more urinary injury (7 vs zero patients),” said Dr. Classe. Mortality was the same in both arms.

There were 314 events observed in the trial, which was 22 events fewer than the required sample size to show superiority. However, Dr. Classe said, a “worst-case scenario” calculation, assuming that all events would have favored lymphadenectomy, did not change the overall result.

The discussant for the trial, Shitanshu Uppal, MD, assistant professor in the division of gynecologic oncology at the University of Michigan in Ann Arbor, agreed that the study investigators adequately addressed this concern with the “counterfactual scenario.” He added that “as utilization of neoadjuvant chemotherapy goes up these results are really helpful in consolidating the results of the prior LION study, that lymph node dissection has no role in interval debulking surgery as well.”

Commenting on the study during the press conference, Michael Lowe, MD, associate professor in the division of surgical oncology at Emory University School of Medicine in Atlanta, said the CARACO study investigators’ efforts “underscore the difficulty of designing and accruing surgical clinical trials, especially clinical trials in which patients are offered less surgery.” He said the trial’s findings are consistent with other clinical trials in breast cancer and melanoma “that likewise showed similar outcomes for patients that did not undergo removal of clinically normal appearing lymph nodes.”

He pointed out that all of these studies highlight that the focus should turn to improving medical therapies.

Echoing this sentiment, Julie Gralow, MD, ASCO chief medical officer and executive vice-president, said, “it is very clear that lymph node dissection has significant morbidity ... and it’s very clear that we should not be doing more surgery than is needed ... In advanced ovarian cancer where the majority already have distant disease [focusing] on systemic therapy is probably what will have the most impact.”

Christina Annunziata, MD, PhD, senior vice president, Extramural Discovery Science, at the American Cancer Society, and an expert in ovarian cancer, said the analysis “leaves little doubt that there would be a statistically significant difference between the two arms. The numbers are small, but since this study results were consistent with the similar LION trial, I think that this study will tip the balance further towards omitting the lymphadenectomy in both primary and interval surgeries,” she said in an interview.

Dr. Annunziata added that surgeons are already omitting the dissection based on the LION study.

The study was funded by the French National Institute of Cancer. Dr. Classe disclosed consulting or advisory roles for GlaxoSmithKline, Myriad Genetics, and Roche.

None of the other experts interviewed for this piece declared having any relevant disclosures.

Routine removal of healthy lymph nodes should not be a part of ovarian cancer treatment, according to results of the CARACO trial.

Retroperitoneal pelvic and para-aortic lymphadenectomy (RPPL) in patients undergoing either primary or interval surgery during ovarian cancer treatment for advanced epithelial ovarian cancer (AEOC) resulted in no benefit and significant harm, the new study found.

“[RPPL] brings only toxicity and it does not increase survival ... because we have a lot of improvement with other treatments than surgery,” lead author Jean-Marc Classe, MD, PhD, said during a press conference at the annual meeting of the American Society of Clinical Oncology. “It’s a surgical de-escalation, because it is not useful.”

Enrollment for the multicenter, phase III CARACO trial stagnated after the LION trial (N Engl J Med . 2019 Feb 28;380[9]:822-832) showed no benefit to doing RPPL in patients undergoing primary surgery for AEOC. Ultimately, the CARACO trial did not enroll the prespecified sample size needed in order for the researchers to show that not doing RPPL was superior. 

Dr. Classe, a surgical oncologist at Nantes Université, in Nantes, France, explained that primary surgery is currently much less common than interval surgery for AEOC , thus it was important to design the CARACO trial to explore the risks and benefits of RPPL in a patient population that included more interval surgery.

CARACO enrolled 379 patients, with median age 64-65 years, and was closed prematurely due to stagnation of enrollment. Patients were randomized to no-RPPL (n = 193) or RPPL (n = 186), with about 75% in each arm receiving interval surgery (neoadjuvant chemotherapy, followed by cytoreductive surgery and adjuvant chemotherapy), and about 25% receiving primary surgery (initial cytoreductive surgery followed by adjuvant chemotherapy). There was a similar postsurgical rate of no residual disease (85.6% and 88.3% in the no-RPPL and RPPL groups, respectively), and lymph node metastases were diagnosed in 43% of the patients in the RPPL arm, with a median of 3 involved lymph nodes.

After a median follow-up of 9 years both the primary endpoint of progression-free survival (PFS), and secondary endpoint of overall survival (OS) showed no advantage to RPPL, with a median PFS of 14.8 months in the no-RPPL arm and 18.5 months in the RPPL arm (HR 0.96), and a median OS of 48.9 months and 58.0 months respectively (HR 0.92).

Surgery in the lymphadenectomy arm was 300 minutes versus 240 minutes.

“We observed statistically significant more morbidity in the lymphadenectomy arm with more transfusion (72 vs 57 patients), more re-intervention (15 vs 6 patients), more urinary injury (7 vs zero patients),” said Dr. Classe. Mortality was the same in both arms.

There were 314 events observed in the trial, which was 22 events fewer than the required sample size to show superiority. However, Dr. Classe said, a “worst-case scenario” calculation, assuming that all events would have favored lymphadenectomy, did not change the overall result.

The discussant for the trial, Shitanshu Uppal, MD, assistant professor in the division of gynecologic oncology at the University of Michigan in Ann Arbor, agreed that the study investigators adequately addressed this concern with the “counterfactual scenario.” He added that “as utilization of neoadjuvant chemotherapy goes up these results are really helpful in consolidating the results of the prior LION study, that lymph node dissection has no role in interval debulking surgery as well.”

Commenting on the study during the press conference, Michael Lowe, MD, associate professor in the division of surgical oncology at Emory University School of Medicine in Atlanta, said the CARACO study investigators’ efforts “underscore the difficulty of designing and accruing surgical clinical trials, especially clinical trials in which patients are offered less surgery.” He said the trial’s findings are consistent with other clinical trials in breast cancer and melanoma “that likewise showed similar outcomes for patients that did not undergo removal of clinically normal appearing lymph nodes.”

He pointed out that all of these studies highlight that the focus should turn to improving medical therapies.

Echoing this sentiment, Julie Gralow, MD, ASCO chief medical officer and executive vice-president, said, “it is very clear that lymph node dissection has significant morbidity ... and it’s very clear that we should not be doing more surgery than is needed ... In advanced ovarian cancer where the majority already have distant disease [focusing] on systemic therapy is probably what will have the most impact.”

Christina Annunziata, MD, PhD, senior vice president, Extramural Discovery Science, at the American Cancer Society, and an expert in ovarian cancer, said the analysis “leaves little doubt that there would be a statistically significant difference between the two arms. The numbers are small, but since this study results were consistent with the similar LION trial, I think that this study will tip the balance further towards omitting the lymphadenectomy in both primary and interval surgeries,” she said in an interview.

Dr. Annunziata added that surgeons are already omitting the dissection based on the LION study.

The study was funded by the French National Institute of Cancer. Dr. Classe disclosed consulting or advisory roles for GlaxoSmithKline, Myriad Genetics, and Roche.

None of the other experts interviewed for this piece declared having any relevant disclosures.

Routine removal of healthy lymph nodes should not be a part of ovarian cancer treatment, according to results of the CARACO trial.

Retroperitoneal pelvic and para-aortic lymphadenectomy (RPPL) in patients undergoing either primary or interval surgery during ovarian cancer treatment for advanced epithelial ovarian cancer (AEOC) resulted in no benefit and significant harm, the new study found.

“[RPPL] brings only toxicity and it does not increase survival ... because we have a lot of improvement with other treatments than surgery,” lead author Jean-Marc Classe, MD, PhD, said during a press conference at the annual meeting of the American Society of Clinical Oncology. “It’s a surgical de-escalation, because it is not useful.”

Enrollment for the multicenter, phase III CARACO trial stagnated after the LION trial (N Engl J Med . 2019 Feb 28;380[9]:822-832) showed no benefit to doing RPPL in patients undergoing primary surgery for AEOC. Ultimately, the CARACO trial did not enroll the prespecified sample size needed in order for the researchers to show that not doing RPPL was superior. 

Dr. Classe, a surgical oncologist at Nantes Université, in Nantes, France, explained that primary surgery is currently much less common than interval surgery for AEOC , thus it was important to design the CARACO trial to explore the risks and benefits of RPPL in a patient population that included more interval surgery.

CARACO enrolled 379 patients, with median age 64-65 years, and was closed prematurely due to stagnation of enrollment. Patients were randomized to no-RPPL (n = 193) or RPPL (n = 186), with about 75% in each arm receiving interval surgery (neoadjuvant chemotherapy, followed by cytoreductive surgery and adjuvant chemotherapy), and about 25% receiving primary surgery (initial cytoreductive surgery followed by adjuvant chemotherapy). There was a similar postsurgical rate of no residual disease (85.6% and 88.3% in the no-RPPL and RPPL groups, respectively), and lymph node metastases were diagnosed in 43% of the patients in the RPPL arm, with a median of 3 involved lymph nodes.

After a median follow-up of 9 years both the primary endpoint of progression-free survival (PFS), and secondary endpoint of overall survival (OS) showed no advantage to RPPL, with a median PFS of 14.8 months in the no-RPPL arm and 18.5 months in the RPPL arm (HR 0.96), and a median OS of 48.9 months and 58.0 months respectively (HR 0.92).

Surgery in the lymphadenectomy arm was 300 minutes versus 240 minutes.

“We observed statistically significant more morbidity in the lymphadenectomy arm with more transfusion (72 vs 57 patients), more re-intervention (15 vs 6 patients), more urinary injury (7 vs zero patients),” said Dr. Classe. Mortality was the same in both arms.

There were 314 events observed in the trial, which was 22 events fewer than the required sample size to show superiority. However, Dr. Classe said, a “worst-case scenario” calculation, assuming that all events would have favored lymphadenectomy, did not change the overall result.

The discussant for the trial, Shitanshu Uppal, MD, assistant professor in the division of gynecologic oncology at the University of Michigan in Ann Arbor, agreed that the study investigators adequately addressed this concern with the “counterfactual scenario.” He added that “as utilization of neoadjuvant chemotherapy goes up these results are really helpful in consolidating the results of the prior LION study, that lymph node dissection has no role in interval debulking surgery as well.”

Commenting on the study during the press conference, Michael Lowe, MD, associate professor in the division of surgical oncology at Emory University School of Medicine in Atlanta, said the CARACO study investigators’ efforts “underscore the difficulty of designing and accruing surgical clinical trials, especially clinical trials in which patients are offered less surgery.” He said the trial’s findings are consistent with other clinical trials in breast cancer and melanoma “that likewise showed similar outcomes for patients that did not undergo removal of clinically normal appearing lymph nodes.”

He pointed out that all of these studies highlight that the focus should turn to improving medical therapies.

Echoing this sentiment, Julie Gralow, MD, ASCO chief medical officer and executive vice-president, said, “it is very clear that lymph node dissection has significant morbidity ... and it’s very clear that we should not be doing more surgery than is needed ... In advanced ovarian cancer where the majority already have distant disease [focusing] on systemic therapy is probably what will have the most impact.”

Christina Annunziata, MD, PhD, senior vice president, Extramural Discovery Science, at the American Cancer Society, and an expert in ovarian cancer, said the analysis “leaves little doubt that there would be a statistically significant difference between the two arms. The numbers are small, but since this study results were consistent with the similar LION trial, I think that this study will tip the balance further towards omitting the lymphadenectomy in both primary and interval surgeries,” she said in an interview.

Dr. Annunziata added that surgeons are already omitting the dissection based on the LION study.

The study was funded by the French National Institute of Cancer. Dr. Classe disclosed consulting or advisory roles for GlaxoSmithKline, Myriad Genetics, and Roche.

None of the other experts interviewed for this piece declared having any relevant disclosures.

Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.

Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.

“Biologic therapy has been shown to reduce exacerbations in type 2 airway inflammation in patients with asthma and may be a potential target in patients with COPD and type 2 inflammation,” he said. In type 2 inflammation, a systematic allergic response activates immune cells, including eosinophils, mast cells, and T cells.

Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.

In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
 

Reduction in Exacerbations and Hospitalizations

The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test). 

In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.

Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.

The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.

“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.

The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.

“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
 

Data Support the Potential of Biologics for COPD

Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.

Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”

The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.

“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.

The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.

Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.

“Biologic therapy has been shown to reduce exacerbations in type 2 airway inflammation in patients with asthma and may be a potential target in patients with COPD and type 2 inflammation,” he said. In type 2 inflammation, a systematic allergic response activates immune cells, including eosinophils, mast cells, and T cells.

Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.

In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
 

Reduction in Exacerbations and Hospitalizations

The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test). 

In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.

Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.

The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.

“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.

The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.

“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
 

Data Support the Potential of Biologics for COPD

Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.

Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”

The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.

“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.

The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.

Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.

“Biologic therapy has been shown to reduce exacerbations in type 2 airway inflammation in patients with asthma and may be a potential target in patients with COPD and type 2 inflammation,” he said. In type 2 inflammation, a systematic allergic response activates immune cells, including eosinophils, mast cells, and T cells.

Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.

In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
 

Reduction in Exacerbations and Hospitalizations

The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test). 

In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.

Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.

The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.

“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.

The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.

“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
 

Data Support the Potential of Biologics for COPD

Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.

Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”

The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.

“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.

The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

The addition of abemaciclib to fulvestrant significantly improved progression-free survival for patients with hormone receptor positive, HER2 negative advanced breast cancer who had been previously treated with cyclin-dependent kinase 4 and 6 inhibitor plus endocrine therapy, in a new study.

Disease progression is common in these patients, for whom first-line treatment is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors plus endocrine therapy, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the American Society of Clinical Oncology (ASCO) annual meeting.

A need exists for additional targeted therapies for patients with advanced hormone receptor (HR)+, HER2- breast cancer whose tumors have progressed on endocrine therapy plus a CDK4/6 inhibitor, he said.

Data on the benefits of continuing CDK4/6 inhibitor therapy after progression have been mixed in phase 2 trials, Dr. Kalinsky noted in his presentation. Abemaciclib, an oral CDK4/6 inhibitor, has shown more selectivity for CDK 4 than CDK 6, and is approved in combination with fulvestrant or an aromatase inhibitor for advanced breast cancer, he said.

In a phase 3 study known as postMONARCH, the researchers randomized 182 patients to abemaciclib plus fulvestrant and 186 to placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS) based on investigator assessment; secondary endpoints included PFS based on blinded independent central review (BICR), objective response rate (ORR), and safety.

The PFS rates at 6 months were 50% and 37% for the abemaciclib and placebo arms, respectively.

In the primary analysis, abemaciclib led to a 27% reduction in risk of investigator-assessed progression-free survival events compared with the placebo (117 vs. 141 events, hazard ratio 0.73, P = 0.02).

The study population included men and pre- and postmenopausal women with advanced HR+, HER2- breast cancer and progression after initial CDK4/6 plus endocrine therapy from 96 centers in 16 countries, enrolled between March 2022 and June 2023. The median age of the patients in the abemaciclib and placebo groups was 58 years and 61 years, respectively. Patients underwent scans every 8 weeks for the first 12 months, then every 12 weeks. Most of the patients were enrolled immediately after CDK4/6i + ET as initial therapy for advanced breast cancer. The most common previous CDK4/6 inhibitor therapy was palbociclib (59%), followed by ribociclib (33%) and abemaciclib (8%).
 

Secondary Endpoints Also Favor Abemaciclib

The effects in favor of abemaciclib were consistent across subgroups, regardless of the presence or absence of baseline genetic mutations (ESR1 or PIK3CA), Dr. Kalinsky said in his presentation.

Overall response rate was significantly improved in the abemaciclib group compared with the placebo group in patients with measurable disease (17% vs. 7%) and PFS according to BICR also significantly improved (HR 0.55).

The magnitude of benefit was less in the subgroup of patients with visceral metastases, Dr. Kalinsky noted.

“Safety was consistent with what is known about the abemaciclib profile,” he added. Six percent of abemaciclib patients discontinued treatment because of adverse events.

The study is the first phase 3 trial to show improvement with CDK4/6 inhibition therapy with a combination of abemaciclib and fulvestrant and offers a new option for patients with HR+, HER2- advanced breast cancer not selected for biomarker status, Dr. Kalinsky concluded.
 

Data Support Switching CDK Inhibitors in Absence of Mutations

Switching CDK inhibitors to abemaciclib plus endocrine therapy significantly prolonged progression-free survival compared with endocrine therapy alone, with especially pronounced improvement in those without visceral metastases and those with longer durations of first-line CKD4/6 inhibitor therapy, said Ruth O’Regan, MD, of the University of Rochester, New York, who served as the discussant for the new research.

Dr. Regan referenced the improvement with abemaciclib in the BICR, a technique used to identify potential bias introduced by the assessment of local investigators. This can result in more favorable PFS on a treatment arm as seen in this study, but its use generally does not impact overall trial results, she said.

In the context of other studies involving switching CDK 4/6 inhibitors post-progression, the difference of 0.7 months in PFS between the abemaciclib and placebo groups was less than the 2.5 months difference seen in the MAINTAIN trial and the 1.3 months difference seen in the PALMIRA trial, Dr. O’Regan said in her presentation. Conversely, in the PACE trial, the intervention group did worse (4.6 months) than the control group in terms of the PFS (4.8 months), she said. Overall, the results of the postMONARCH trial support the use abemaciclib in patients with no actionable genetic mutation, she said.

In a question-and-answer session, Dr. Kalinsky was asked whether clinicians should still bother with genetic testing, since patients in the current study showed benefits regardless of the presence or absence of a mutation.

“I would still recommend that we check for mutations,” he emphasized. The current study “is one chapter in a much larger book,” and the field continues to evolve, he said.
 

A Clinician’s Take

“Currently, no standard second-line treatment after progression on first line CDK4/6 inhibitor plus endocrine therapy exists,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. “Using a different CDK4/6 inhibitor after progression on a first CDK4/6 inhibitor has mixed data,” she said.

“If benefit with a second CDK4/6 inhibitor is confirmed, it may represent an additional low toxicity, chemotherapy-sparing regimen,” she noted.

Earlier data from the MAINTAIN trial had shown benefit with using ribociclib after progression on a primarily first line palbociclib, though other trials looking at use of palbociclib after progression on CDK 4/6 inhibitor [including the PACE and PALMIRA trials] had not, she said.

Overall, the results from postMONARCH support that switching the CDK4/6 inhibitor at progression to ribociclib or abemaciclib may be another treatment option, and reasonable for patients who don’t have other actionable mutations, Dr. West told this news organization.

The study was supported by Eli Lilly. Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma; AstraZeneca; Cullinan Oncology; Daiichi Sankyo/AstraZeneca; eFFECTOR Therapeutics; Genentech/Roche; Immunomedics; Lilly; Menarini Silicon Biosystems; Merck; Mersana; Myovant Sciences; Novartis; Oncosec; Prelude Therapeutics; Puma Biotechnology; RayzeBio; Seagen; and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma; AstraZeneca; Daiichi Sankyo; Genentech/Roche; Lilly; Novartis; and Seagen, and relationships with Genentech and Immunomedics.

Dr. O’Regan disclosed honoraria from AstraZeneca/MedImmune; bioTheranostics; Gilead Sciences; Novartis; Pfizer; Puma Biotechnology; and Seagen, serving as a consultant or adviser for AstraZeneca/MedImmune; bioTheranostics; Lilly; Novartis; Puma Biotechnology; and Seagen, and funding to her institution from Novartis and Puma Biotechnology.

Dr. West, who was not involved in the new research or other studies mentioned in this article, had no financial conflicts to disclose.

The addition of abemaciclib to fulvestrant significantly improved progression-free survival for patients with hormone receptor positive, HER2 negative advanced breast cancer who had been previously treated with cyclin-dependent kinase 4 and 6 inhibitor plus endocrine therapy, in a new study.

Disease progression is common in these patients, for whom first-line treatment is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors plus endocrine therapy, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the American Society of Clinical Oncology (ASCO) annual meeting.

A need exists for additional targeted therapies for patients with advanced hormone receptor (HR)+, HER2- breast cancer whose tumors have progressed on endocrine therapy plus a CDK4/6 inhibitor, he said.

Data on the benefits of continuing CDK4/6 inhibitor therapy after progression have been mixed in phase 2 trials, Dr. Kalinsky noted in his presentation. Abemaciclib, an oral CDK4/6 inhibitor, has shown more selectivity for CDK 4 than CDK 6, and is approved in combination with fulvestrant or an aromatase inhibitor for advanced breast cancer, he said.

In a phase 3 study known as postMONARCH, the researchers randomized 182 patients to abemaciclib plus fulvestrant and 186 to placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS) based on investigator assessment; secondary endpoints included PFS based on blinded independent central review (BICR), objective response rate (ORR), and safety.

The PFS rates at 6 months were 50% and 37% for the abemaciclib and placebo arms, respectively.

In the primary analysis, abemaciclib led to a 27% reduction in risk of investigator-assessed progression-free survival events compared with the placebo (117 vs. 141 events, hazard ratio 0.73, P = 0.02).

The study population included men and pre- and postmenopausal women with advanced HR+, HER2- breast cancer and progression after initial CDK4/6 plus endocrine therapy from 96 centers in 16 countries, enrolled between March 2022 and June 2023. The median age of the patients in the abemaciclib and placebo groups was 58 years and 61 years, respectively. Patients underwent scans every 8 weeks for the first 12 months, then every 12 weeks. Most of the patients were enrolled immediately after CDK4/6i + ET as initial therapy for advanced breast cancer. The most common previous CDK4/6 inhibitor therapy was palbociclib (59%), followed by ribociclib (33%) and abemaciclib (8%).
 

Secondary Endpoints Also Favor Abemaciclib

The effects in favor of abemaciclib were consistent across subgroups, regardless of the presence or absence of baseline genetic mutations (ESR1 or PIK3CA), Dr. Kalinsky said in his presentation.

Overall response rate was significantly improved in the abemaciclib group compared with the placebo group in patients with measurable disease (17% vs. 7%) and PFS according to BICR also significantly improved (HR 0.55).

The magnitude of benefit was less in the subgroup of patients with visceral metastases, Dr. Kalinsky noted.

“Safety was consistent with what is known about the abemaciclib profile,” he added. Six percent of abemaciclib patients discontinued treatment because of adverse events.

The study is the first phase 3 trial to show improvement with CDK4/6 inhibition therapy with a combination of abemaciclib and fulvestrant and offers a new option for patients with HR+, HER2- advanced breast cancer not selected for biomarker status, Dr. Kalinsky concluded.
 

Data Support Switching CDK Inhibitors in Absence of Mutations

Switching CDK inhibitors to abemaciclib plus endocrine therapy significantly prolonged progression-free survival compared with endocrine therapy alone, with especially pronounced improvement in those without visceral metastases and those with longer durations of first-line CKD4/6 inhibitor therapy, said Ruth O’Regan, MD, of the University of Rochester, New York, who served as the discussant for the new research.

Dr. Regan referenced the improvement with abemaciclib in the BICR, a technique used to identify potential bias introduced by the assessment of local investigators. This can result in more favorable PFS on a treatment arm as seen in this study, but its use generally does not impact overall trial results, she said.

In the context of other studies involving switching CDK 4/6 inhibitors post-progression, the difference of 0.7 months in PFS between the abemaciclib and placebo groups was less than the 2.5 months difference seen in the MAINTAIN trial and the 1.3 months difference seen in the PALMIRA trial, Dr. O’Regan said in her presentation. Conversely, in the PACE trial, the intervention group did worse (4.6 months) than the control group in terms of the PFS (4.8 months), she said. Overall, the results of the postMONARCH trial support the use abemaciclib in patients with no actionable genetic mutation, she said.

In a question-and-answer session, Dr. Kalinsky was asked whether clinicians should still bother with genetic testing, since patients in the current study showed benefits regardless of the presence or absence of a mutation.

“I would still recommend that we check for mutations,” he emphasized. The current study “is one chapter in a much larger book,” and the field continues to evolve, he said.
 

A Clinician’s Take

“Currently, no standard second-line treatment after progression on first line CDK4/6 inhibitor plus endocrine therapy exists,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. “Using a different CDK4/6 inhibitor after progression on a first CDK4/6 inhibitor has mixed data,” she said.

“If benefit with a second CDK4/6 inhibitor is confirmed, it may represent an additional low toxicity, chemotherapy-sparing regimen,” she noted.

Earlier data from the MAINTAIN trial had shown benefit with using ribociclib after progression on a primarily first line palbociclib, though other trials looking at use of palbociclib after progression on CDK 4/6 inhibitor [including the PACE and PALMIRA trials] had not, she said.

Overall, the results from postMONARCH support that switching the CDK4/6 inhibitor at progression to ribociclib or abemaciclib may be another treatment option, and reasonable for patients who don’t have other actionable mutations, Dr. West told this news organization.

The study was supported by Eli Lilly. Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma; AstraZeneca; Cullinan Oncology; Daiichi Sankyo/AstraZeneca; eFFECTOR Therapeutics; Genentech/Roche; Immunomedics; Lilly; Menarini Silicon Biosystems; Merck; Mersana; Myovant Sciences; Novartis; Oncosec; Prelude Therapeutics; Puma Biotechnology; RayzeBio; Seagen; and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma; AstraZeneca; Daiichi Sankyo; Genentech/Roche; Lilly; Novartis; and Seagen, and relationships with Genentech and Immunomedics.

Dr. O’Regan disclosed honoraria from AstraZeneca/MedImmune; bioTheranostics; Gilead Sciences; Novartis; Pfizer; Puma Biotechnology; and Seagen, serving as a consultant or adviser for AstraZeneca/MedImmune; bioTheranostics; Lilly; Novartis; Puma Biotechnology; and Seagen, and funding to her institution from Novartis and Puma Biotechnology.

Dr. West, who was not involved in the new research or other studies mentioned in this article, had no financial conflicts to disclose.

The addition of abemaciclib to fulvestrant significantly improved progression-free survival for patients with hormone receptor positive, HER2 negative advanced breast cancer who had been previously treated with cyclin-dependent kinase 4 and 6 inhibitor plus endocrine therapy, in a new study.

Disease progression is common in these patients, for whom first-line treatment is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors plus endocrine therapy, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the American Society of Clinical Oncology (ASCO) annual meeting.

A need exists for additional targeted therapies for patients with advanced hormone receptor (HR)+, HER2- breast cancer whose tumors have progressed on endocrine therapy plus a CDK4/6 inhibitor, he said.

Data on the benefits of continuing CDK4/6 inhibitor therapy after progression have been mixed in phase 2 trials, Dr. Kalinsky noted in his presentation. Abemaciclib, an oral CDK4/6 inhibitor, has shown more selectivity for CDK 4 than CDK 6, and is approved in combination with fulvestrant or an aromatase inhibitor for advanced breast cancer, he said.

In a phase 3 study known as postMONARCH, the researchers randomized 182 patients to abemaciclib plus fulvestrant and 186 to placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS) based on investigator assessment; secondary endpoints included PFS based on blinded independent central review (BICR), objective response rate (ORR), and safety.

The PFS rates at 6 months were 50% and 37% for the abemaciclib and placebo arms, respectively.

In the primary analysis, abemaciclib led to a 27% reduction in risk of investigator-assessed progression-free survival events compared with the placebo (117 vs. 141 events, hazard ratio 0.73, P = 0.02).

The study population included men and pre- and postmenopausal women with advanced HR+, HER2- breast cancer and progression after initial CDK4/6 plus endocrine therapy from 96 centers in 16 countries, enrolled between March 2022 and June 2023. The median age of the patients in the abemaciclib and placebo groups was 58 years and 61 years, respectively. Patients underwent scans every 8 weeks for the first 12 months, then every 12 weeks. Most of the patients were enrolled immediately after CDK4/6i + ET as initial therapy for advanced breast cancer. The most common previous CDK4/6 inhibitor therapy was palbociclib (59%), followed by ribociclib (33%) and abemaciclib (8%).
 

Secondary Endpoints Also Favor Abemaciclib

The effects in favor of abemaciclib were consistent across subgroups, regardless of the presence or absence of baseline genetic mutations (ESR1 or PIK3CA), Dr. Kalinsky said in his presentation.

Overall response rate was significantly improved in the abemaciclib group compared with the placebo group in patients with measurable disease (17% vs. 7%) and PFS according to BICR also significantly improved (HR 0.55).

The magnitude of benefit was less in the subgroup of patients with visceral metastases, Dr. Kalinsky noted.

“Safety was consistent with what is known about the abemaciclib profile,” he added. Six percent of abemaciclib patients discontinued treatment because of adverse events.

The study is the first phase 3 trial to show improvement with CDK4/6 inhibition therapy with a combination of abemaciclib and fulvestrant and offers a new option for patients with HR+, HER2- advanced breast cancer not selected for biomarker status, Dr. Kalinsky concluded.
 

Data Support Switching CDK Inhibitors in Absence of Mutations

Switching CDK inhibitors to abemaciclib plus endocrine therapy significantly prolonged progression-free survival compared with endocrine therapy alone, with especially pronounced improvement in those without visceral metastases and those with longer durations of first-line CKD4/6 inhibitor therapy, said Ruth O’Regan, MD, of the University of Rochester, New York, who served as the discussant for the new research.

Dr. Regan referenced the improvement with abemaciclib in the BICR, a technique used to identify potential bias introduced by the assessment of local investigators. This can result in more favorable PFS on a treatment arm as seen in this study, but its use generally does not impact overall trial results, she said.

In the context of other studies involving switching CDK 4/6 inhibitors post-progression, the difference of 0.7 months in PFS between the abemaciclib and placebo groups was less than the 2.5 months difference seen in the MAINTAIN trial and the 1.3 months difference seen in the PALMIRA trial, Dr. O’Regan said in her presentation. Conversely, in the PACE trial, the intervention group did worse (4.6 months) than the control group in terms of the PFS (4.8 months), she said. Overall, the results of the postMONARCH trial support the use abemaciclib in patients with no actionable genetic mutation, she said.

In a question-and-answer session, Dr. Kalinsky was asked whether clinicians should still bother with genetic testing, since patients in the current study showed benefits regardless of the presence or absence of a mutation.

“I would still recommend that we check for mutations,” he emphasized. The current study “is one chapter in a much larger book,” and the field continues to evolve, he said.
 

A Clinician’s Take

“Currently, no standard second-line treatment after progression on first line CDK4/6 inhibitor plus endocrine therapy exists,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. “Using a different CDK4/6 inhibitor after progression on a first CDK4/6 inhibitor has mixed data,” she said.

“If benefit with a second CDK4/6 inhibitor is confirmed, it may represent an additional low toxicity, chemotherapy-sparing regimen,” she noted.

Earlier data from the MAINTAIN trial had shown benefit with using ribociclib after progression on a primarily first line palbociclib, though other trials looking at use of palbociclib after progression on CDK 4/6 inhibitor [including the PACE and PALMIRA trials] had not, she said.

Overall, the results from postMONARCH support that switching the CDK4/6 inhibitor at progression to ribociclib or abemaciclib may be another treatment option, and reasonable for patients who don’t have other actionable mutations, Dr. West told this news organization.

The study was supported by Eli Lilly. Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma; AstraZeneca; Cullinan Oncology; Daiichi Sankyo/AstraZeneca; eFFECTOR Therapeutics; Genentech/Roche; Immunomedics; Lilly; Menarini Silicon Biosystems; Merck; Mersana; Myovant Sciences; Novartis; Oncosec; Prelude Therapeutics; Puma Biotechnology; RayzeBio; Seagen; and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma; AstraZeneca; Daiichi Sankyo; Genentech/Roche; Lilly; Novartis; and Seagen, and relationships with Genentech and Immunomedics.

Dr. O’Regan disclosed honoraria from AstraZeneca/MedImmune; bioTheranostics; Gilead Sciences; Novartis; Pfizer; Puma Biotechnology; and Seagen, serving as a consultant or adviser for AstraZeneca/MedImmune; bioTheranostics; Lilly; Novartis; Puma Biotechnology; and Seagen, and funding to her institution from Novartis and Puma Biotechnology.

Dr. West, who was not involved in the new research or other studies mentioned in this article, had no financial conflicts to disclose.