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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Metabolic abnormalities boost obesity-related cancer risk
, and an even higher risk, two- to threefold higher, for specific cancers, such as endometrial, liver, and renal cell cancers, compared with metabolically healthy normal weight.
Even in people with so-called “metabolically healthy” obesity, the risk for overall obesity-related cancer is increased, compared with normal-weight, metabolically healthy individuals; however, the associations here are weaker than in people with metabolically unhealthy obesity.
“The type of metabolic obesity phenotype is important when assessing obesity-related cancer risk,” lead researcher Ming Sun, PhD, from Lund University, Malmö, Sweden, said in an interview. “In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.”
“This synergy means that when obesity and metabolic unhealth occur together, that’s particularly bad,” added Tanja Stocks, PhD, senior author, also of Lund University.
“But the data also highlight that even obesity and overweight alone comprise an increased risk of cancer,” Dr. Stocks noted.
Dr. Sun said the findings have important public health implications, suggesting that “a significant number of cancer cases could potentially be prevented by targeting the coexistence of metabolic problems and obesity, in particular for obesity-related cancers among men.”
The results will be presented as a poster by Dr. Sun at the European Congress on Obesity 2023, being held in Dublin, and have been published in the Journal of the National Cancer Institute.
Metabolically unhealthy obesity worst for cancer risks
Andrew G. Renehan, PhD, FRCS, professor of cancer studies and surgery, University of Manchester, England, welcomed the new work, saying it addresses the issue with very large study numbers. “[It] nicely demonstrates that there are clear examples where metabolically unhealthy overweight and obese phenotypes have increased cancer risk relative to [metabolically] healthy overweight and obese phenotypes,” he said.
“There is a clear need for clinically based research addressing these hypotheses ... but these studies will additionally need to factor in other dimensions such as the selection of treatment for metabolic aberrations, both medical and surgical, and the consequent metabolic control resulting from these interventions,” Dr. Renehan observed.
Vibhu Chittajallu, MD, a gastroenterologist based at University Hospitals Cleveland Medical Center, said it was beneficial to see another study further validating the association of obesity with the development of obesity-associated cancers.
“This is an interesting study [because it focuses] on the role of metabolic syndrome in obesity and how it affects the risk of development of obesity-associated cancers,” he said in an interview.
“I believe that the results of this study further strengthen the need for improved management of obesity and metabolic syndrome to reduce the risk of obesity-associated cancer formation that plays a role in preventable and premature deaths in adult patients with obesity.”
Synergy between metabolic aberrations and obesity, and cancer risk
Dr. Sun and colleagues note that obesity is an established risk factor for several cancers. It is often accompanied by metabolic aberrations, which have been a commonly proposed mechanism to link obesity with cancer. During the last decade, obesity with or without metabolic aberrations – commonly termed “metabolically unhealthy” or “healthy obesity” – has been extensively investigated in the cardiovascular field; however, studies regarding cancer are limited.
According to Dr. Sun, this new study is the first to look at the synergistic effect of unhealthy metabolism and body mass index – the latter was further categorized as normal weight (BMI < 25 kg/m2), overweight (BMI < 30) and obesity (BMI ≤ 30) – and the association with cancer risk, both overall and in relation to site-specific cancers.
Data were drawn from 797,193 European individuals (in Norway, Sweden, and Austria), of whom 23,630 developed an obesity-related cancer during the follow-up period. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to provide a measure of healthy or unhealthy metabolic status. Relative risks (hazard ratios) for overall and site-specific cancers were determined. Comparisons were made with metabolically healthy people of normal weight (effectively controls).
When different metabolic scores and BMIs were combined, participants fell into six categories: metabolically unhealthy obesity (6.8% of participants); metabolically healthy obesity (3.4%), metabolically unhealthy overweight (15.4%), metabolically healthy overweight (19.8%), metabolically unhealthy normal weight (12.5%), and metabolically healthy normal weight (42.0%).
Metabolically unhealthy women with obesity had a hazard ratio of 1.43 for overall obesity-related cancers, compared with metabolically healthy women of normal weight. Of particular note were risks of two cancer types in women with metabolically unhealthy obesity: renal cancer, with an HR of 2.43, and endometrial cancer, with an HR of 3.0, compared with controls.
Even in metabolically healthy women with obesity, compared with metabolically healthy women of normal weight, there was an increased risk of endometrial cancer, with an HR of 2.36.
“If you look at individual cancers, in particular endometrial cancer, this seems to be very much driven by obesity and not so much by the metabolic factor,” remarked Dr. Stocks.
In males, compared with metabolically healthy men of normal weight, metabolically unhealthy men with obesity had an overall obesity-related cancer risk HR of 1.91. Specifically, the risk of renal cell cancer was more than doubled, with an HR of 2.59. The HR for colon cancer was 1.85, and that for rectal cancer and pancreatic cancer was similar, both having HRs of 1.32.
Again, risk was lower in metabolically healthy men with obesity, although still higher than for metabolically healthy normal-weight men.
A version of this article first appeared on Medscape.com.
, and an even higher risk, two- to threefold higher, for specific cancers, such as endometrial, liver, and renal cell cancers, compared with metabolically healthy normal weight.
Even in people with so-called “metabolically healthy” obesity, the risk for overall obesity-related cancer is increased, compared with normal-weight, metabolically healthy individuals; however, the associations here are weaker than in people with metabolically unhealthy obesity.
“The type of metabolic obesity phenotype is important when assessing obesity-related cancer risk,” lead researcher Ming Sun, PhD, from Lund University, Malmö, Sweden, said in an interview. “In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.”
“This synergy means that when obesity and metabolic unhealth occur together, that’s particularly bad,” added Tanja Stocks, PhD, senior author, also of Lund University.
“But the data also highlight that even obesity and overweight alone comprise an increased risk of cancer,” Dr. Stocks noted.
Dr. Sun said the findings have important public health implications, suggesting that “a significant number of cancer cases could potentially be prevented by targeting the coexistence of metabolic problems and obesity, in particular for obesity-related cancers among men.”
The results will be presented as a poster by Dr. Sun at the European Congress on Obesity 2023, being held in Dublin, and have been published in the Journal of the National Cancer Institute.
Metabolically unhealthy obesity worst for cancer risks
Andrew G. Renehan, PhD, FRCS, professor of cancer studies and surgery, University of Manchester, England, welcomed the new work, saying it addresses the issue with very large study numbers. “[It] nicely demonstrates that there are clear examples where metabolically unhealthy overweight and obese phenotypes have increased cancer risk relative to [metabolically] healthy overweight and obese phenotypes,” he said.
“There is a clear need for clinically based research addressing these hypotheses ... but these studies will additionally need to factor in other dimensions such as the selection of treatment for metabolic aberrations, both medical and surgical, and the consequent metabolic control resulting from these interventions,” Dr. Renehan observed.
Vibhu Chittajallu, MD, a gastroenterologist based at University Hospitals Cleveland Medical Center, said it was beneficial to see another study further validating the association of obesity with the development of obesity-associated cancers.
“This is an interesting study [because it focuses] on the role of metabolic syndrome in obesity and how it affects the risk of development of obesity-associated cancers,” he said in an interview.
“I believe that the results of this study further strengthen the need for improved management of obesity and metabolic syndrome to reduce the risk of obesity-associated cancer formation that plays a role in preventable and premature deaths in adult patients with obesity.”
Synergy between metabolic aberrations and obesity, and cancer risk
Dr. Sun and colleagues note that obesity is an established risk factor for several cancers. It is often accompanied by metabolic aberrations, which have been a commonly proposed mechanism to link obesity with cancer. During the last decade, obesity with or without metabolic aberrations – commonly termed “metabolically unhealthy” or “healthy obesity” – has been extensively investigated in the cardiovascular field; however, studies regarding cancer are limited.
According to Dr. Sun, this new study is the first to look at the synergistic effect of unhealthy metabolism and body mass index – the latter was further categorized as normal weight (BMI < 25 kg/m2), overweight (BMI < 30) and obesity (BMI ≤ 30) – and the association with cancer risk, both overall and in relation to site-specific cancers.
Data were drawn from 797,193 European individuals (in Norway, Sweden, and Austria), of whom 23,630 developed an obesity-related cancer during the follow-up period. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to provide a measure of healthy or unhealthy metabolic status. Relative risks (hazard ratios) for overall and site-specific cancers were determined. Comparisons were made with metabolically healthy people of normal weight (effectively controls).
When different metabolic scores and BMIs were combined, participants fell into six categories: metabolically unhealthy obesity (6.8% of participants); metabolically healthy obesity (3.4%), metabolically unhealthy overweight (15.4%), metabolically healthy overweight (19.8%), metabolically unhealthy normal weight (12.5%), and metabolically healthy normal weight (42.0%).
Metabolically unhealthy women with obesity had a hazard ratio of 1.43 for overall obesity-related cancers, compared with metabolically healthy women of normal weight. Of particular note were risks of two cancer types in women with metabolically unhealthy obesity: renal cancer, with an HR of 2.43, and endometrial cancer, with an HR of 3.0, compared with controls.
Even in metabolically healthy women with obesity, compared with metabolically healthy women of normal weight, there was an increased risk of endometrial cancer, with an HR of 2.36.
“If you look at individual cancers, in particular endometrial cancer, this seems to be very much driven by obesity and not so much by the metabolic factor,” remarked Dr. Stocks.
In males, compared with metabolically healthy men of normal weight, metabolically unhealthy men with obesity had an overall obesity-related cancer risk HR of 1.91. Specifically, the risk of renal cell cancer was more than doubled, with an HR of 2.59. The HR for colon cancer was 1.85, and that for rectal cancer and pancreatic cancer was similar, both having HRs of 1.32.
Again, risk was lower in metabolically healthy men with obesity, although still higher than for metabolically healthy normal-weight men.
A version of this article first appeared on Medscape.com.
, and an even higher risk, two- to threefold higher, for specific cancers, such as endometrial, liver, and renal cell cancers, compared with metabolically healthy normal weight.
Even in people with so-called “metabolically healthy” obesity, the risk for overall obesity-related cancer is increased, compared with normal-weight, metabolically healthy individuals; however, the associations here are weaker than in people with metabolically unhealthy obesity.
“The type of metabolic obesity phenotype is important when assessing obesity-related cancer risk,” lead researcher Ming Sun, PhD, from Lund University, Malmö, Sweden, said in an interview. “In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.”
“This synergy means that when obesity and metabolic unhealth occur together, that’s particularly bad,” added Tanja Stocks, PhD, senior author, also of Lund University.
“But the data also highlight that even obesity and overweight alone comprise an increased risk of cancer,” Dr. Stocks noted.
Dr. Sun said the findings have important public health implications, suggesting that “a significant number of cancer cases could potentially be prevented by targeting the coexistence of metabolic problems and obesity, in particular for obesity-related cancers among men.”
The results will be presented as a poster by Dr. Sun at the European Congress on Obesity 2023, being held in Dublin, and have been published in the Journal of the National Cancer Institute.
Metabolically unhealthy obesity worst for cancer risks
Andrew G. Renehan, PhD, FRCS, professor of cancer studies and surgery, University of Manchester, England, welcomed the new work, saying it addresses the issue with very large study numbers. “[It] nicely demonstrates that there are clear examples where metabolically unhealthy overweight and obese phenotypes have increased cancer risk relative to [metabolically] healthy overweight and obese phenotypes,” he said.
“There is a clear need for clinically based research addressing these hypotheses ... but these studies will additionally need to factor in other dimensions such as the selection of treatment for metabolic aberrations, both medical and surgical, and the consequent metabolic control resulting from these interventions,” Dr. Renehan observed.
Vibhu Chittajallu, MD, a gastroenterologist based at University Hospitals Cleveland Medical Center, said it was beneficial to see another study further validating the association of obesity with the development of obesity-associated cancers.
“This is an interesting study [because it focuses] on the role of metabolic syndrome in obesity and how it affects the risk of development of obesity-associated cancers,” he said in an interview.
“I believe that the results of this study further strengthen the need for improved management of obesity and metabolic syndrome to reduce the risk of obesity-associated cancer formation that plays a role in preventable and premature deaths in adult patients with obesity.”
Synergy between metabolic aberrations and obesity, and cancer risk
Dr. Sun and colleagues note that obesity is an established risk factor for several cancers. It is often accompanied by metabolic aberrations, which have been a commonly proposed mechanism to link obesity with cancer. During the last decade, obesity with or without metabolic aberrations – commonly termed “metabolically unhealthy” or “healthy obesity” – has been extensively investigated in the cardiovascular field; however, studies regarding cancer are limited.
According to Dr. Sun, this new study is the first to look at the synergistic effect of unhealthy metabolism and body mass index – the latter was further categorized as normal weight (BMI < 25 kg/m2), overweight (BMI < 30) and obesity (BMI ≤ 30) – and the association with cancer risk, both overall and in relation to site-specific cancers.
Data were drawn from 797,193 European individuals (in Norway, Sweden, and Austria), of whom 23,630 developed an obesity-related cancer during the follow-up period. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to provide a measure of healthy or unhealthy metabolic status. Relative risks (hazard ratios) for overall and site-specific cancers were determined. Comparisons were made with metabolically healthy people of normal weight (effectively controls).
When different metabolic scores and BMIs were combined, participants fell into six categories: metabolically unhealthy obesity (6.8% of participants); metabolically healthy obesity (3.4%), metabolically unhealthy overweight (15.4%), metabolically healthy overweight (19.8%), metabolically unhealthy normal weight (12.5%), and metabolically healthy normal weight (42.0%).
Metabolically unhealthy women with obesity had a hazard ratio of 1.43 for overall obesity-related cancers, compared with metabolically healthy women of normal weight. Of particular note were risks of two cancer types in women with metabolically unhealthy obesity: renal cancer, with an HR of 2.43, and endometrial cancer, with an HR of 3.0, compared with controls.
Even in metabolically healthy women with obesity, compared with metabolically healthy women of normal weight, there was an increased risk of endometrial cancer, with an HR of 2.36.
“If you look at individual cancers, in particular endometrial cancer, this seems to be very much driven by obesity and not so much by the metabolic factor,” remarked Dr. Stocks.
In males, compared with metabolically healthy men of normal weight, metabolically unhealthy men with obesity had an overall obesity-related cancer risk HR of 1.91. Specifically, the risk of renal cell cancer was more than doubled, with an HR of 2.59. The HR for colon cancer was 1.85, and that for rectal cancer and pancreatic cancer was similar, both having HRs of 1.32.
Again, risk was lower in metabolically healthy men with obesity, although still higher than for metabolically healthy normal-weight men.
A version of this article first appeared on Medscape.com.
FROM ECO 2023
Patritumab deruxtecan shows promise for breast cancer patients
according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.
Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.
Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.
In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.
In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.
Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.
All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.
At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049).
In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).
Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.
HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.
A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.
To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.
During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
ICARUS-BREAST01
In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.
The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.
The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.
After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.
As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.
Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.
“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.
In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.
Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.
In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.
Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.
Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
Early results merit further exploration
Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.
“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.
In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.
“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.
The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.
“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”
In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.
The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.
according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.
Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.
Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.
In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.
In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.
Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.
All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.
At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049).
In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).
Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.
HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.
A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.
To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.
During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
ICARUS-BREAST01
In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.
The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.
The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.
After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.
As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.
Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.
“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.
In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.
Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.
In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.
Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.
Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
Early results merit further exploration
Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.
“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.
In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.
“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.
The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.
“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”
In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.
The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.
according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.
Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.
Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.
In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.
In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.
Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.
All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.
At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049).
In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).
Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.
HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.
A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.
To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.
During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
ICARUS-BREAST01
In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.
The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.
The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.
After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.
As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.
Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.
“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.
In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.
Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.
In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.
Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.
Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
Early results merit further exploration
Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.
“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.
In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.
“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.
The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.
“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”
In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.
The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.
FROM ESMO BREAST CANCER 2023
Noninvasive skin test may aid in Cushing diagnosis
SEATTLE – new research suggests.
Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.
The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.
“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.
“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.
Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”
However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.
Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
More work will be needed
Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.
“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”
Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”
But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”
Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SEATTLE – new research suggests.
Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.
The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.
“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.
“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.
Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”
However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.
Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
More work will be needed
Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.
“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”
Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”
But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”
Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SEATTLE – new research suggests.
Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.
The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.
“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.
“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.
Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”
However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.
Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
More work will be needed
Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.
“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”
Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”
But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”
Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AACE 2023
Men underrepresented in clinical trials of laser hair removal, review finds
PHOENIX – .
To characterize the sex of patients in trials evaluating hair removal with energy-based devices, Dr. Lee, an internal medicine intern at Beth Israel Deaconess Medical Center, Boston, and Jessica Labadie, MD, director of lasers and cosmetic surgery at the Icahn School of Medicine at Mount Sinai, New York, conducted a systematic review using PubMed with the search query hair AND laser AND removal AND (dermatology OR skin OR cutaneous). They limited the analysis to English-language clinical trials that investigated a laser and light-based therapy as an intervention and if hair reduction was an outcome, and excluded studies that did not include the face as a treatment area and laser hair removal for diseases with disproportionate occurrence in females or males, such as polycystic ovarian syndrome or pseudofolliculitis barbae.
Of 121 articles identified from the PubMed search, 28 studies involving 3,882 patients treated with lasers or intense pulsed light (IPL) for hair removal were included in the final analysis. Of these 28 articles, 22 (79%) reported the sex of trial participants. The population of these 22 studies included 3,104 (88.7%) females, 384 (11.0%) males, and 11 (0.003%) nonbinary identifying patients. None of the studies evaluated laser hair removal outcomes by sex.
“This study adds to the current knowledge of laser hair removal as a part of gender-affirming care by characterizing the representation of assigned sexes of patients in clinical trials evaluating the effectiveness of laser hair removal,” Dr. Lee told this news organization. “It highlights the underrepresentation of people assigned to male sex at birth in these clinical trials, despite this population’s potential interest in laser hair removal as a part of gender-affirming care.”
She acknowledged certain limitations of the review, including the absence of reporting on sex in the demographic sections of many trials and the exclusion of trials that did not include treatment of the face. “Clinicians need to be aware of the underrepresentation of men in clinical trials evaluating laser hair removal, and this may limit their understanding of treatment outcomes in this particular cohort,” she concluded. “Clinicians should emphasize inclusivity in future laser hair removal clinical trials and include outcomes by sex.”
The study “looks at an important aspect of clinical trials in the device-based space,” said Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, who was not involved in the study and was asked to comment on the results. “Laser hair removal is the most commonly performed procedure in aesthetic energy-based device dermatology. While these trials are often very small compared to drug trials, it highlights that men are a very underrepresented cohort in laser hair removal trials,” he said. “More recently, there is an increased interest in gender-affirming procedures, and this has highlighted the need to ensure we include a diverse spectrum of patients in devices-based research studies. This is a very challenging mandate but certainly one we should strive for to make efforts to be more inclusive when designing these clinical studies so that the information we gain from these studies is more broadly applicable.”
The researchers reported having no financial disclosures. Dr. Ibrahimi disclosed that he is a member of the advisory board for Accure Acne, AbbVie, Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero, and holds stock in many device and pharmaceutical companies.
PHOENIX – .
To characterize the sex of patients in trials evaluating hair removal with energy-based devices, Dr. Lee, an internal medicine intern at Beth Israel Deaconess Medical Center, Boston, and Jessica Labadie, MD, director of lasers and cosmetic surgery at the Icahn School of Medicine at Mount Sinai, New York, conducted a systematic review using PubMed with the search query hair AND laser AND removal AND (dermatology OR skin OR cutaneous). They limited the analysis to English-language clinical trials that investigated a laser and light-based therapy as an intervention and if hair reduction was an outcome, and excluded studies that did not include the face as a treatment area and laser hair removal for diseases with disproportionate occurrence in females or males, such as polycystic ovarian syndrome or pseudofolliculitis barbae.
Of 121 articles identified from the PubMed search, 28 studies involving 3,882 patients treated with lasers or intense pulsed light (IPL) for hair removal were included in the final analysis. Of these 28 articles, 22 (79%) reported the sex of trial participants. The population of these 22 studies included 3,104 (88.7%) females, 384 (11.0%) males, and 11 (0.003%) nonbinary identifying patients. None of the studies evaluated laser hair removal outcomes by sex.
“This study adds to the current knowledge of laser hair removal as a part of gender-affirming care by characterizing the representation of assigned sexes of patients in clinical trials evaluating the effectiveness of laser hair removal,” Dr. Lee told this news organization. “It highlights the underrepresentation of people assigned to male sex at birth in these clinical trials, despite this population’s potential interest in laser hair removal as a part of gender-affirming care.”
She acknowledged certain limitations of the review, including the absence of reporting on sex in the demographic sections of many trials and the exclusion of trials that did not include treatment of the face. “Clinicians need to be aware of the underrepresentation of men in clinical trials evaluating laser hair removal, and this may limit their understanding of treatment outcomes in this particular cohort,” she concluded. “Clinicians should emphasize inclusivity in future laser hair removal clinical trials and include outcomes by sex.”
The study “looks at an important aspect of clinical trials in the device-based space,” said Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, who was not involved in the study and was asked to comment on the results. “Laser hair removal is the most commonly performed procedure in aesthetic energy-based device dermatology. While these trials are often very small compared to drug trials, it highlights that men are a very underrepresented cohort in laser hair removal trials,” he said. “More recently, there is an increased interest in gender-affirming procedures, and this has highlighted the need to ensure we include a diverse spectrum of patients in devices-based research studies. This is a very challenging mandate but certainly one we should strive for to make efforts to be more inclusive when designing these clinical studies so that the information we gain from these studies is more broadly applicable.”
The researchers reported having no financial disclosures. Dr. Ibrahimi disclosed that he is a member of the advisory board for Accure Acne, AbbVie, Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero, and holds stock in many device and pharmaceutical companies.
PHOENIX – .
To characterize the sex of patients in trials evaluating hair removal with energy-based devices, Dr. Lee, an internal medicine intern at Beth Israel Deaconess Medical Center, Boston, and Jessica Labadie, MD, director of lasers and cosmetic surgery at the Icahn School of Medicine at Mount Sinai, New York, conducted a systematic review using PubMed with the search query hair AND laser AND removal AND (dermatology OR skin OR cutaneous). They limited the analysis to English-language clinical trials that investigated a laser and light-based therapy as an intervention and if hair reduction was an outcome, and excluded studies that did not include the face as a treatment area and laser hair removal for diseases with disproportionate occurrence in females or males, such as polycystic ovarian syndrome or pseudofolliculitis barbae.
Of 121 articles identified from the PubMed search, 28 studies involving 3,882 patients treated with lasers or intense pulsed light (IPL) for hair removal were included in the final analysis. Of these 28 articles, 22 (79%) reported the sex of trial participants. The population of these 22 studies included 3,104 (88.7%) females, 384 (11.0%) males, and 11 (0.003%) nonbinary identifying patients. None of the studies evaluated laser hair removal outcomes by sex.
“This study adds to the current knowledge of laser hair removal as a part of gender-affirming care by characterizing the representation of assigned sexes of patients in clinical trials evaluating the effectiveness of laser hair removal,” Dr. Lee told this news organization. “It highlights the underrepresentation of people assigned to male sex at birth in these clinical trials, despite this population’s potential interest in laser hair removal as a part of gender-affirming care.”
She acknowledged certain limitations of the review, including the absence of reporting on sex in the demographic sections of many trials and the exclusion of trials that did not include treatment of the face. “Clinicians need to be aware of the underrepresentation of men in clinical trials evaluating laser hair removal, and this may limit their understanding of treatment outcomes in this particular cohort,” she concluded. “Clinicians should emphasize inclusivity in future laser hair removal clinical trials and include outcomes by sex.”
The study “looks at an important aspect of clinical trials in the device-based space,” said Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, who was not involved in the study and was asked to comment on the results. “Laser hair removal is the most commonly performed procedure in aesthetic energy-based device dermatology. While these trials are often very small compared to drug trials, it highlights that men are a very underrepresented cohort in laser hair removal trials,” he said. “More recently, there is an increased interest in gender-affirming procedures, and this has highlighted the need to ensure we include a diverse spectrum of patients in devices-based research studies. This is a very challenging mandate but certainly one we should strive for to make efforts to be more inclusive when designing these clinical studies so that the information we gain from these studies is more broadly applicable.”
The researchers reported having no financial disclosures. Dr. Ibrahimi disclosed that he is a member of the advisory board for Accure Acne, AbbVie, Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero, and holds stock in many device and pharmaceutical companies.
AT ASLMS 2023
Facial, hand, and foot dermatitis: Lebrikizumab and dupilumab show efficacy in new studies
in a secondary analysis of randomized, double-blind, placebo-controlled phase 3 trials of the drug, Jenny E. Murase, MD, reported at the annual Revolutionizing Atopic Dermatitis conference.
At week 16 in the ADvocate 1, ADvocate 2, and ADhere trials, with and without concomitant topical corticosteroid (TCS) use, at least 58% of treated patients experienced improvement in facial dermatitis, and 62% or more experienced improvement in hand dermatitis – statistically significant differences over placebo.
“Lebrikizumab was efficacious in clearing and improving facial and hand dermatitis, burdensome and difficult-to-treat areas, in most patients with moderate to severe AD,” said Dr. Murase, of the department of dermatology at the University of California, San Francisco, and director of medical dermatology consultative services and patch testing for the Palo Alto (Calf.) Foundation Medical Group.
In another late-breaking abstract presented at the RAD conference, the injectable biologic dupilumab – now in its 6th year on the market – was reported by Jonathan I. Silverberg, MD, PhD, MPH, to “rapidly and significantly” improve the signs, symptoms, and quality of life in some adults and adolescents with moderate to severe hand and foot AD in a recently completed phase 3 trial of dupilumab.
Lebrikizumab results for facial, hand dermatitis
The ADvocate 1 and ADvocate 2 trials evaluated lebrikizumab monotherapy and randomized patients to receive 250 mg subcutaneously every 2 weeks (after a 500-mg loading dose at baseline and week 2) or placebo. (Patients who received any corticosteroid as a rescue medication were considered nonresponders.) The ADhere trial compared low to mid–potency TCS plus lebrikizumab, using the same dosing of lebrikizumab as in the ADvocate studies, versus TCS plus placebo.
In all three trials, with a total of more than 1,000 participants, clinicians assessed for the presence or absence of facial or hand dermatitis at baseline. At week 16, they then assessed the change from baseline based on a 4-point scale of cleared, improved, no change, and worsened. “Improvement” was defined as cleared or improved.
Both facial and hand dermatitis were identified in a majority of patients at baseline. For instance, in ADvocate 1, facial dermatitis was identified in 71.4% of patients in the lebrikizumab group and 80.9% of those in the placebo group. Hand dermatitis was identified in 72% and 73% of the treatment and placebo groups, respectively.
Across the trials, at 16 weeks, 58%-69% of adult and adolescent patients receiving lebrikizumab had improvement in facial dermatitis, compared with 22%-46% on placebo. For hand dermatitis, 62%-73% experienced improvement, compared with 19%-43% on placebo, respectively. Proportions of improved patients in both the lebrikizumab and placebo groups were highest in the ADhere trial, Dr. Murase reported.
In the ADvocate trials, 16 weeks marked the end of the induction phase and the start of a 36-week maintenance period. The ADhere trial was a 16-week study. Overall results from ADhere were published in January in JAMA Dermatology, and results from the 16-week induction period of the ADvocate trials were published in March in the New England Journal of Medicine.
Lebrikizumab received fast-track designation for AD by the Food and Drug Administration in 2019. Regulatory decisions in the United States and the European Union are expected later this year, according to a press release from Eli Lilly, the drug’s developer.
Asked to comment on the study results, Zelma Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, called the post-hoc results promising. “While newer, more targeted treatments for AD offer the possibility of overall improvement and long-term disease control, we do not have sufficient data to help guide us when it comes to selecting treatment based on which area of the body is affected,” she explained. Most published findings have used “overall scores and not scores stratified by body region.”
The new findings, “help expand our current understanding of how the drug works for different areas of the body,” which can help inform treatment discussions with patients, she added.
AD can be especially challenging to treat when it involves “what are considered to be more sensitive areas such as the face or hands,” said Dr. Chiesa Fuxench. Challenges may include poor tolerance to topical medications, concerns for safety with long-term use, and the need for constant reapplication.
“Those of us who treat a large number of AD patients suspect that the impact and/or burden of AD may be different depending on what areas of the body are affected,” but more data are needed, she added. Limitations of the study, she noted, include “that the study may not have been adequately powered and that the sample size was small.”
Dupilumab result for hand, foot dermatitis
The phase 3 LIBERTY-AD-HAFT trial randomized 133 patients with moderate to severe atopic hand and/or foot dermatitis to a 16-week course of dupilumab (Dupixent) monotherapy, 300 mg every 2 weeks in adults and 200 or 300 mg every 2 weeks in adolescents, or placebo. Patients were then followed during a 12-week safety follow-up period.
Significantly more patients in the dupilumab group achieved the primary endpoint of a hand and foot Investigator Global Assessment (IGA) score of 0/1 at 16 weeks: 40.3% vs. 16.7% in the placebo group (P = .003). Statistical significance was reached at week 8, reported Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University, Washington. Dupilumab, a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling, is FDA approved for treating moderate to severe AD in patients age 6 months and older, among other indications.
In addition, the proportion of patients achieving a 4-point or greater improvement in the weekly average of daily hand and foot Peak Pruritus Numerical Rating Scale (PPNRS), the key secondary endpoint, was about fourfold greater with dupilumab: 52.2%, compared with 13.6% on placebo (P < .0001). This reduction in itch reached statistical significance by week 1. Dupilumab-treated patients also experienced significant improvement in other lesion measures and in Quality of Life in Hand Eczema Questionnaire scores, Dr. Silverberg noted.
The patients had a mean age in their 30s and a mean duration of atopic hand and/or foot dermatitis of 15-16 years. For more than one-quarter of patients, morphology was hyperkeratotic, which “has to be one of the toughest subsets to affect positive change in,” he said.
About 40% of patients had lesions on the hands only, and more than half had lesions on both hands and feet. “This is pretty realistic – we generally don’t see much isolated foot dermatitis in the AD population,” Dr. Silverberg said.
About 70%-75% had concomitant AD outside of the hands and feet, mostly of moderate severity. Patients with positive patch tests or whose hand and foot eczema was believed to be driven by irritants were excluded from the trial, as were patients who had used TCS or other topical treatments within 2 weeks of the baseline visit.
Rescue medication use was low (3% with dupilumab vs. 21% with placebo), and adverse events were “pretty consistent with everything we’ve seen with dupilumab,” said Dr. Silverberg.
Commenting on this study, Dr. Chiesa Fuxench said she was “excited to see [the findings], as hand and foot AD can often be quite challenging to treat in clinic.” The improvements in overall disease scores, itch, and quality of life scores – with fairly good tolerance – are “reassuring and what we would expect based on our current experience with dupilumab,” she said.
The lebrikizumab study was funded by Dermira, a wholly owned subsidiary of Eli Lilly. The dupilumab study was sponsored by Sanofi and Regeneron Pharmaceuticals. Some of the data were also reported by lead investigator Eric Simpson, MD, of Oregon Health and Science University at the annual meeting of the American Academy of Dermatology in March 2023.
Dr. Murase reported consulting/advising for Eli Lilly, Leo Pharma, UCB, Sanofi-Genzyme, and non-CME speaking/honoraria for UCB and Regeneron. Dr. Silverberg reported consulting fees and fees for non-CME services from Sanofi Genzyme, Regeneron, Pfizer, and other companies. Dr. Chiesa Fuxench, who was a speaker at the RAD meeting but was not involved in the studies, disclosed receiving honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi, and grant/research support from Lilly, Regeneron, and Sanofi, among other disclosures.
in a secondary analysis of randomized, double-blind, placebo-controlled phase 3 trials of the drug, Jenny E. Murase, MD, reported at the annual Revolutionizing Atopic Dermatitis conference.
At week 16 in the ADvocate 1, ADvocate 2, and ADhere trials, with and without concomitant topical corticosteroid (TCS) use, at least 58% of treated patients experienced improvement in facial dermatitis, and 62% or more experienced improvement in hand dermatitis – statistically significant differences over placebo.
“Lebrikizumab was efficacious in clearing and improving facial and hand dermatitis, burdensome and difficult-to-treat areas, in most patients with moderate to severe AD,” said Dr. Murase, of the department of dermatology at the University of California, San Francisco, and director of medical dermatology consultative services and patch testing for the Palo Alto (Calf.) Foundation Medical Group.
In another late-breaking abstract presented at the RAD conference, the injectable biologic dupilumab – now in its 6th year on the market – was reported by Jonathan I. Silverberg, MD, PhD, MPH, to “rapidly and significantly” improve the signs, symptoms, and quality of life in some adults and adolescents with moderate to severe hand and foot AD in a recently completed phase 3 trial of dupilumab.
Lebrikizumab results for facial, hand dermatitis
The ADvocate 1 and ADvocate 2 trials evaluated lebrikizumab monotherapy and randomized patients to receive 250 mg subcutaneously every 2 weeks (after a 500-mg loading dose at baseline and week 2) or placebo. (Patients who received any corticosteroid as a rescue medication were considered nonresponders.) The ADhere trial compared low to mid–potency TCS plus lebrikizumab, using the same dosing of lebrikizumab as in the ADvocate studies, versus TCS plus placebo.
In all three trials, with a total of more than 1,000 participants, clinicians assessed for the presence or absence of facial or hand dermatitis at baseline. At week 16, they then assessed the change from baseline based on a 4-point scale of cleared, improved, no change, and worsened. “Improvement” was defined as cleared or improved.
Both facial and hand dermatitis were identified in a majority of patients at baseline. For instance, in ADvocate 1, facial dermatitis was identified in 71.4% of patients in the lebrikizumab group and 80.9% of those in the placebo group. Hand dermatitis was identified in 72% and 73% of the treatment and placebo groups, respectively.
Across the trials, at 16 weeks, 58%-69% of adult and adolescent patients receiving lebrikizumab had improvement in facial dermatitis, compared with 22%-46% on placebo. For hand dermatitis, 62%-73% experienced improvement, compared with 19%-43% on placebo, respectively. Proportions of improved patients in both the lebrikizumab and placebo groups were highest in the ADhere trial, Dr. Murase reported.
In the ADvocate trials, 16 weeks marked the end of the induction phase and the start of a 36-week maintenance period. The ADhere trial was a 16-week study. Overall results from ADhere were published in January in JAMA Dermatology, and results from the 16-week induction period of the ADvocate trials were published in March in the New England Journal of Medicine.
Lebrikizumab received fast-track designation for AD by the Food and Drug Administration in 2019. Regulatory decisions in the United States and the European Union are expected later this year, according to a press release from Eli Lilly, the drug’s developer.
Asked to comment on the study results, Zelma Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, called the post-hoc results promising. “While newer, more targeted treatments for AD offer the possibility of overall improvement and long-term disease control, we do not have sufficient data to help guide us when it comes to selecting treatment based on which area of the body is affected,” she explained. Most published findings have used “overall scores and not scores stratified by body region.”
The new findings, “help expand our current understanding of how the drug works for different areas of the body,” which can help inform treatment discussions with patients, she added.
AD can be especially challenging to treat when it involves “what are considered to be more sensitive areas such as the face or hands,” said Dr. Chiesa Fuxench. Challenges may include poor tolerance to topical medications, concerns for safety with long-term use, and the need for constant reapplication.
“Those of us who treat a large number of AD patients suspect that the impact and/or burden of AD may be different depending on what areas of the body are affected,” but more data are needed, she added. Limitations of the study, she noted, include “that the study may not have been adequately powered and that the sample size was small.”
Dupilumab result for hand, foot dermatitis
The phase 3 LIBERTY-AD-HAFT trial randomized 133 patients with moderate to severe atopic hand and/or foot dermatitis to a 16-week course of dupilumab (Dupixent) monotherapy, 300 mg every 2 weeks in adults and 200 or 300 mg every 2 weeks in adolescents, or placebo. Patients were then followed during a 12-week safety follow-up period.
Significantly more patients in the dupilumab group achieved the primary endpoint of a hand and foot Investigator Global Assessment (IGA) score of 0/1 at 16 weeks: 40.3% vs. 16.7% in the placebo group (P = .003). Statistical significance was reached at week 8, reported Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University, Washington. Dupilumab, a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling, is FDA approved for treating moderate to severe AD in patients age 6 months and older, among other indications.
In addition, the proportion of patients achieving a 4-point or greater improvement in the weekly average of daily hand and foot Peak Pruritus Numerical Rating Scale (PPNRS), the key secondary endpoint, was about fourfold greater with dupilumab: 52.2%, compared with 13.6% on placebo (P < .0001). This reduction in itch reached statistical significance by week 1. Dupilumab-treated patients also experienced significant improvement in other lesion measures and in Quality of Life in Hand Eczema Questionnaire scores, Dr. Silverberg noted.
The patients had a mean age in their 30s and a mean duration of atopic hand and/or foot dermatitis of 15-16 years. For more than one-quarter of patients, morphology was hyperkeratotic, which “has to be one of the toughest subsets to affect positive change in,” he said.
About 40% of patients had lesions on the hands only, and more than half had lesions on both hands and feet. “This is pretty realistic – we generally don’t see much isolated foot dermatitis in the AD population,” Dr. Silverberg said.
About 70%-75% had concomitant AD outside of the hands and feet, mostly of moderate severity. Patients with positive patch tests or whose hand and foot eczema was believed to be driven by irritants were excluded from the trial, as were patients who had used TCS or other topical treatments within 2 weeks of the baseline visit.
Rescue medication use was low (3% with dupilumab vs. 21% with placebo), and adverse events were “pretty consistent with everything we’ve seen with dupilumab,” said Dr. Silverberg.
Commenting on this study, Dr. Chiesa Fuxench said she was “excited to see [the findings], as hand and foot AD can often be quite challenging to treat in clinic.” The improvements in overall disease scores, itch, and quality of life scores – with fairly good tolerance – are “reassuring and what we would expect based on our current experience with dupilumab,” she said.
The lebrikizumab study was funded by Dermira, a wholly owned subsidiary of Eli Lilly. The dupilumab study was sponsored by Sanofi and Regeneron Pharmaceuticals. Some of the data were also reported by lead investigator Eric Simpson, MD, of Oregon Health and Science University at the annual meeting of the American Academy of Dermatology in March 2023.
Dr. Murase reported consulting/advising for Eli Lilly, Leo Pharma, UCB, Sanofi-Genzyme, and non-CME speaking/honoraria for UCB and Regeneron. Dr. Silverberg reported consulting fees and fees for non-CME services from Sanofi Genzyme, Regeneron, Pfizer, and other companies. Dr. Chiesa Fuxench, who was a speaker at the RAD meeting but was not involved in the studies, disclosed receiving honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi, and grant/research support from Lilly, Regeneron, and Sanofi, among other disclosures.
in a secondary analysis of randomized, double-blind, placebo-controlled phase 3 trials of the drug, Jenny E. Murase, MD, reported at the annual Revolutionizing Atopic Dermatitis conference.
At week 16 in the ADvocate 1, ADvocate 2, and ADhere trials, with and without concomitant topical corticosteroid (TCS) use, at least 58% of treated patients experienced improvement in facial dermatitis, and 62% or more experienced improvement in hand dermatitis – statistically significant differences over placebo.
“Lebrikizumab was efficacious in clearing and improving facial and hand dermatitis, burdensome and difficult-to-treat areas, in most patients with moderate to severe AD,” said Dr. Murase, of the department of dermatology at the University of California, San Francisco, and director of medical dermatology consultative services and patch testing for the Palo Alto (Calf.) Foundation Medical Group.
In another late-breaking abstract presented at the RAD conference, the injectable biologic dupilumab – now in its 6th year on the market – was reported by Jonathan I. Silverberg, MD, PhD, MPH, to “rapidly and significantly” improve the signs, symptoms, and quality of life in some adults and adolescents with moderate to severe hand and foot AD in a recently completed phase 3 trial of dupilumab.
Lebrikizumab results for facial, hand dermatitis
The ADvocate 1 and ADvocate 2 trials evaluated lebrikizumab monotherapy and randomized patients to receive 250 mg subcutaneously every 2 weeks (after a 500-mg loading dose at baseline and week 2) or placebo. (Patients who received any corticosteroid as a rescue medication were considered nonresponders.) The ADhere trial compared low to mid–potency TCS plus lebrikizumab, using the same dosing of lebrikizumab as in the ADvocate studies, versus TCS plus placebo.
In all three trials, with a total of more than 1,000 participants, clinicians assessed for the presence or absence of facial or hand dermatitis at baseline. At week 16, they then assessed the change from baseline based on a 4-point scale of cleared, improved, no change, and worsened. “Improvement” was defined as cleared or improved.
Both facial and hand dermatitis were identified in a majority of patients at baseline. For instance, in ADvocate 1, facial dermatitis was identified in 71.4% of patients in the lebrikizumab group and 80.9% of those in the placebo group. Hand dermatitis was identified in 72% and 73% of the treatment and placebo groups, respectively.
Across the trials, at 16 weeks, 58%-69% of adult and adolescent patients receiving lebrikizumab had improvement in facial dermatitis, compared with 22%-46% on placebo. For hand dermatitis, 62%-73% experienced improvement, compared with 19%-43% on placebo, respectively. Proportions of improved patients in both the lebrikizumab and placebo groups were highest in the ADhere trial, Dr. Murase reported.
In the ADvocate trials, 16 weeks marked the end of the induction phase and the start of a 36-week maintenance period. The ADhere trial was a 16-week study. Overall results from ADhere were published in January in JAMA Dermatology, and results from the 16-week induction period of the ADvocate trials were published in March in the New England Journal of Medicine.
Lebrikizumab received fast-track designation for AD by the Food and Drug Administration in 2019. Regulatory decisions in the United States and the European Union are expected later this year, according to a press release from Eli Lilly, the drug’s developer.
Asked to comment on the study results, Zelma Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, called the post-hoc results promising. “While newer, more targeted treatments for AD offer the possibility of overall improvement and long-term disease control, we do not have sufficient data to help guide us when it comes to selecting treatment based on which area of the body is affected,” she explained. Most published findings have used “overall scores and not scores stratified by body region.”
The new findings, “help expand our current understanding of how the drug works for different areas of the body,” which can help inform treatment discussions with patients, she added.
AD can be especially challenging to treat when it involves “what are considered to be more sensitive areas such as the face or hands,” said Dr. Chiesa Fuxench. Challenges may include poor tolerance to topical medications, concerns for safety with long-term use, and the need for constant reapplication.
“Those of us who treat a large number of AD patients suspect that the impact and/or burden of AD may be different depending on what areas of the body are affected,” but more data are needed, she added. Limitations of the study, she noted, include “that the study may not have been adequately powered and that the sample size was small.”
Dupilumab result for hand, foot dermatitis
The phase 3 LIBERTY-AD-HAFT trial randomized 133 patients with moderate to severe atopic hand and/or foot dermatitis to a 16-week course of dupilumab (Dupixent) monotherapy, 300 mg every 2 weeks in adults and 200 or 300 mg every 2 weeks in adolescents, or placebo. Patients were then followed during a 12-week safety follow-up period.
Significantly more patients in the dupilumab group achieved the primary endpoint of a hand and foot Investigator Global Assessment (IGA) score of 0/1 at 16 weeks: 40.3% vs. 16.7% in the placebo group (P = .003). Statistical significance was reached at week 8, reported Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University, Washington. Dupilumab, a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling, is FDA approved for treating moderate to severe AD in patients age 6 months and older, among other indications.
In addition, the proportion of patients achieving a 4-point or greater improvement in the weekly average of daily hand and foot Peak Pruritus Numerical Rating Scale (PPNRS), the key secondary endpoint, was about fourfold greater with dupilumab: 52.2%, compared with 13.6% on placebo (P < .0001). This reduction in itch reached statistical significance by week 1. Dupilumab-treated patients also experienced significant improvement in other lesion measures and in Quality of Life in Hand Eczema Questionnaire scores, Dr. Silverberg noted.
The patients had a mean age in their 30s and a mean duration of atopic hand and/or foot dermatitis of 15-16 years. For more than one-quarter of patients, morphology was hyperkeratotic, which “has to be one of the toughest subsets to affect positive change in,” he said.
About 40% of patients had lesions on the hands only, and more than half had lesions on both hands and feet. “This is pretty realistic – we generally don’t see much isolated foot dermatitis in the AD population,” Dr. Silverberg said.
About 70%-75% had concomitant AD outside of the hands and feet, mostly of moderate severity. Patients with positive patch tests or whose hand and foot eczema was believed to be driven by irritants were excluded from the trial, as were patients who had used TCS or other topical treatments within 2 weeks of the baseline visit.
Rescue medication use was low (3% with dupilumab vs. 21% with placebo), and adverse events were “pretty consistent with everything we’ve seen with dupilumab,” said Dr. Silverberg.
Commenting on this study, Dr. Chiesa Fuxench said she was “excited to see [the findings], as hand and foot AD can often be quite challenging to treat in clinic.” The improvements in overall disease scores, itch, and quality of life scores – with fairly good tolerance – are “reassuring and what we would expect based on our current experience with dupilumab,” she said.
The lebrikizumab study was funded by Dermira, a wholly owned subsidiary of Eli Lilly. The dupilumab study was sponsored by Sanofi and Regeneron Pharmaceuticals. Some of the data were also reported by lead investigator Eric Simpson, MD, of Oregon Health and Science University at the annual meeting of the American Academy of Dermatology in March 2023.
Dr. Murase reported consulting/advising for Eli Lilly, Leo Pharma, UCB, Sanofi-Genzyme, and non-CME speaking/honoraria for UCB and Regeneron. Dr. Silverberg reported consulting fees and fees for non-CME services from Sanofi Genzyme, Regeneron, Pfizer, and other companies. Dr. Chiesa Fuxench, who was a speaker at the RAD meeting but was not involved in the studies, disclosed receiving honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi, and grant/research support from Lilly, Regeneron, and Sanofi, among other disclosures.
AT RAD 2023
T-DXd for HER2-low BC: Analysis confirms adverse effects
Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.
In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”
However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.
For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”
Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).
A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.
Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)
ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.
Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.
In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”
In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”
Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”
The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.
The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).
The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.
Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.
In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”
However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.
For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”
Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).
A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.
Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)
ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.
Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.
In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”
In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”
Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”
The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.
The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).
The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.
Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.
In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”
However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.
For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”
Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).
A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.
Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)
ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.
Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.
In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”
In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”
Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”
The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.
The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).
The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.
FROM ESMO BREAST CANCER 2023
At-home monitoring device can predict Crohn’s disease flares
CHICAGO – , including an inability to signal a change in disease activity without laboratory testing or before symptoms arise.
A new device developed at Massachusetts Institute of Technology could change all that.
Using data collected via a passive at-home monitoring device (Emerald sensor, Emerald Innovations Inc.), researchers found that increases in breathing rate, more awakenings at night, and slower walking speed accurately predicted that a person’s Crohn’s disease activity was about to flare, according to a study presented May 7 at Digestive Disease Week® (DDW) 2023.
In some cases, the prediction of a flare came up to 25 days sooner than via traditional measures.
“In order to provide optimal care, providers need to monitor patients closely with regard to accurate active disease.” said Joshua Korzenik, MD, a gastroenterologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School in Boston. “The problem is the clinical symptoms are not accurate.”
Tracking flares with technology
Traditionally, measuring flares in Crohn’s disease activity depends on imaging, colonoscopy, and/or laboratory measures of calprotectin or other biomarkers. These approaches can be costly, can involve delays, and can carry risks, Dr. Korzenik said.
“They are also a single snapshot in time,” he added.
To determine how well a noninvasive device could perform, investigators enrolled 120 people with 105 continuing in the study long enough to be evaluable; 44 people whose Crohn’s disease was in remission, 35 with active Crohn’s disease, as well as 26 healthy controls. Among those with Crohn’s disease, 83% were on biologic therapy.
The groups were matched for age and gender, with a mean age of 47 years and mean disease duration of 13 years.
People with certain medical conditions were excluded, as was anyone who owned a large dog that sometimes slept in bed with them because that might throw off the readings.
The participants put the device – which resembles a closed laptop or a large Wi-Fi router – in their homes and were monitored for a mean 306 days. Participants wore an ankle bracelet the first 2 weeks of the study so the device could learn to distinguish them from others in the home.
The device sent out radio waves with frequencies like Wi-Fi for researchers to measure the factors that may be associated with flares, such as sleep quality and cycles, breathing rate, and gait speed.
Traditional clinical measures based on blood and stool samples, along with patient-reported outcome surveys, were taken to compare with the accuracy of the device.
Data from the device were collected and transmitted securely to a cloud database without any interaction from the participant. Data included information on more than 25,000 nights of sleep, 200,000 hours of breathing signals, and 400,000 measurements of walking speed.
Sleep quality and cycles were straightforward, as was breathing rate. But gait speed was a little more complicated to measure. To illustrate, Dr. Korzenik showed the layout of an example apartment with data on how someone moved around. To distill the data, the researchers focused on one path in the home, relatively straight and not obstructed by furniture, and limited the measurements to a certain amount of time. People who spent more time at home during the COVID-19 pandemic did not skew the results, according to Dr. Korzenik, who added that it wasn’t total time walking around but a snippet in time.
A variety of sleep, breathing, and mobility metrics extracted by the device were integrated to assess disease activity. Investigators noted that during flares, sleep quality decreased, and more nocturnal awakenings occurred. They also found that gait speed slowed, and respiratory rate increased with flares.
When the investigators looked at sleep as a function of disease activity in the patient-reported surveys, they found a significant difference between people in remission and those with active disease. For example, people with active disease had a greater number of awakenings at night (P = .0016), less REM sleep at night (P = .0000), and less time in deep sleep (P = .000) compared with those in remission.
The technology “can identify flares with a predictive value that approaches fecal calprotectin,” Dr. Korzenik said.
Machine learning was used to look at severity of disease vs. fecal calprotectin values and “showed the data could be used as a marker of disease,” he added.
Use of a remote monitor, the comparison of validated vs. conventional data, and the large dataset were among the strengths of the study. The single-center design and exclusion of people with some comorbidities are potential limitations.
Further studies are warranted to confirm these findings and guide optimal care of people with Crohn’s disease, the investigators noted.
Earlier detection, earlier intervention
“The study is really important,” said session comoderator Raymond K. Cross Jr., MD, professor of medicine and director of the IBD program at the University of Maryland, Baltimore.
Monitoring devices like this “could be very useful,” Dr. Cross said. “It is not invasive, unless you consider a device in your house invasive. But, to me, I don’t think a box in my bedroom would be unnerving to me.”
Dr. Cross shared a couple of caveats. “The one devil in the details is always going to be cost,” he said. Also, it’s unclear who will read and interpret all the data generated by the device among “providers who are already overwhelmed with the volume of information.”
Moving forward, a device like this could offer multiple uses, Dr. Cross noted. If the device can detect relapses earlier, physicians could intervene sooner, he said. Also, the device could potentially flag people who are not taking their medications as recommended, or it could be used as a guide to optimize treatment response.
Whether data from the device could indicate when it’s appropriate to reduce the frequency or dose of medication or even when to withdraw therapy would be “really aspirational,” Dr. Cross added.
The study was funded by The Leona M. and Harry B. Helmsley Charitable Trust. Dr. Korzenik and Dr. Cross report no relevant financial relationships.
DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).
A version of this article first appeared on Medscape.com.
CHICAGO – , including an inability to signal a change in disease activity without laboratory testing or before symptoms arise.
A new device developed at Massachusetts Institute of Technology could change all that.
Using data collected via a passive at-home monitoring device (Emerald sensor, Emerald Innovations Inc.), researchers found that increases in breathing rate, more awakenings at night, and slower walking speed accurately predicted that a person’s Crohn’s disease activity was about to flare, according to a study presented May 7 at Digestive Disease Week® (DDW) 2023.
In some cases, the prediction of a flare came up to 25 days sooner than via traditional measures.
“In order to provide optimal care, providers need to monitor patients closely with regard to accurate active disease.” said Joshua Korzenik, MD, a gastroenterologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School in Boston. “The problem is the clinical symptoms are not accurate.”
Tracking flares with technology
Traditionally, measuring flares in Crohn’s disease activity depends on imaging, colonoscopy, and/or laboratory measures of calprotectin or other biomarkers. These approaches can be costly, can involve delays, and can carry risks, Dr. Korzenik said.
“They are also a single snapshot in time,” he added.
To determine how well a noninvasive device could perform, investigators enrolled 120 people with 105 continuing in the study long enough to be evaluable; 44 people whose Crohn’s disease was in remission, 35 with active Crohn’s disease, as well as 26 healthy controls. Among those with Crohn’s disease, 83% were on biologic therapy.
The groups were matched for age and gender, with a mean age of 47 years and mean disease duration of 13 years.
People with certain medical conditions were excluded, as was anyone who owned a large dog that sometimes slept in bed with them because that might throw off the readings.
The participants put the device – which resembles a closed laptop or a large Wi-Fi router – in their homes and were monitored for a mean 306 days. Participants wore an ankle bracelet the first 2 weeks of the study so the device could learn to distinguish them from others in the home.
The device sent out radio waves with frequencies like Wi-Fi for researchers to measure the factors that may be associated with flares, such as sleep quality and cycles, breathing rate, and gait speed.
Traditional clinical measures based on blood and stool samples, along with patient-reported outcome surveys, were taken to compare with the accuracy of the device.
Data from the device were collected and transmitted securely to a cloud database without any interaction from the participant. Data included information on more than 25,000 nights of sleep, 200,000 hours of breathing signals, and 400,000 measurements of walking speed.
Sleep quality and cycles were straightforward, as was breathing rate. But gait speed was a little more complicated to measure. To illustrate, Dr. Korzenik showed the layout of an example apartment with data on how someone moved around. To distill the data, the researchers focused on one path in the home, relatively straight and not obstructed by furniture, and limited the measurements to a certain amount of time. People who spent more time at home during the COVID-19 pandemic did not skew the results, according to Dr. Korzenik, who added that it wasn’t total time walking around but a snippet in time.
A variety of sleep, breathing, and mobility metrics extracted by the device were integrated to assess disease activity. Investigators noted that during flares, sleep quality decreased, and more nocturnal awakenings occurred. They also found that gait speed slowed, and respiratory rate increased with flares.
When the investigators looked at sleep as a function of disease activity in the patient-reported surveys, they found a significant difference between people in remission and those with active disease. For example, people with active disease had a greater number of awakenings at night (P = .0016), less REM sleep at night (P = .0000), and less time in deep sleep (P = .000) compared with those in remission.
The technology “can identify flares with a predictive value that approaches fecal calprotectin,” Dr. Korzenik said.
Machine learning was used to look at severity of disease vs. fecal calprotectin values and “showed the data could be used as a marker of disease,” he added.
Use of a remote monitor, the comparison of validated vs. conventional data, and the large dataset were among the strengths of the study. The single-center design and exclusion of people with some comorbidities are potential limitations.
Further studies are warranted to confirm these findings and guide optimal care of people with Crohn’s disease, the investigators noted.
Earlier detection, earlier intervention
“The study is really important,” said session comoderator Raymond K. Cross Jr., MD, professor of medicine and director of the IBD program at the University of Maryland, Baltimore.
Monitoring devices like this “could be very useful,” Dr. Cross said. “It is not invasive, unless you consider a device in your house invasive. But, to me, I don’t think a box in my bedroom would be unnerving to me.”
Dr. Cross shared a couple of caveats. “The one devil in the details is always going to be cost,” he said. Also, it’s unclear who will read and interpret all the data generated by the device among “providers who are already overwhelmed with the volume of information.”
Moving forward, a device like this could offer multiple uses, Dr. Cross noted. If the device can detect relapses earlier, physicians could intervene sooner, he said. Also, the device could potentially flag people who are not taking their medications as recommended, or it could be used as a guide to optimize treatment response.
Whether data from the device could indicate when it’s appropriate to reduce the frequency or dose of medication or even when to withdraw therapy would be “really aspirational,” Dr. Cross added.
The study was funded by The Leona M. and Harry B. Helmsley Charitable Trust. Dr. Korzenik and Dr. Cross report no relevant financial relationships.
DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).
A version of this article first appeared on Medscape.com.
CHICAGO – , including an inability to signal a change in disease activity without laboratory testing or before symptoms arise.
A new device developed at Massachusetts Institute of Technology could change all that.
Using data collected via a passive at-home monitoring device (Emerald sensor, Emerald Innovations Inc.), researchers found that increases in breathing rate, more awakenings at night, and slower walking speed accurately predicted that a person’s Crohn’s disease activity was about to flare, according to a study presented May 7 at Digestive Disease Week® (DDW) 2023.
In some cases, the prediction of a flare came up to 25 days sooner than via traditional measures.
“In order to provide optimal care, providers need to monitor patients closely with regard to accurate active disease.” said Joshua Korzenik, MD, a gastroenterologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School in Boston. “The problem is the clinical symptoms are not accurate.”
Tracking flares with technology
Traditionally, measuring flares in Crohn’s disease activity depends on imaging, colonoscopy, and/or laboratory measures of calprotectin or other biomarkers. These approaches can be costly, can involve delays, and can carry risks, Dr. Korzenik said.
“They are also a single snapshot in time,” he added.
To determine how well a noninvasive device could perform, investigators enrolled 120 people with 105 continuing in the study long enough to be evaluable; 44 people whose Crohn’s disease was in remission, 35 with active Crohn’s disease, as well as 26 healthy controls. Among those with Crohn’s disease, 83% were on biologic therapy.
The groups were matched for age and gender, with a mean age of 47 years and mean disease duration of 13 years.
People with certain medical conditions were excluded, as was anyone who owned a large dog that sometimes slept in bed with them because that might throw off the readings.
The participants put the device – which resembles a closed laptop or a large Wi-Fi router – in their homes and were monitored for a mean 306 days. Participants wore an ankle bracelet the first 2 weeks of the study so the device could learn to distinguish them from others in the home.
The device sent out radio waves with frequencies like Wi-Fi for researchers to measure the factors that may be associated with flares, such as sleep quality and cycles, breathing rate, and gait speed.
Traditional clinical measures based on blood and stool samples, along with patient-reported outcome surveys, were taken to compare with the accuracy of the device.
Data from the device were collected and transmitted securely to a cloud database without any interaction from the participant. Data included information on more than 25,000 nights of sleep, 200,000 hours of breathing signals, and 400,000 measurements of walking speed.
Sleep quality and cycles were straightforward, as was breathing rate. But gait speed was a little more complicated to measure. To illustrate, Dr. Korzenik showed the layout of an example apartment with data on how someone moved around. To distill the data, the researchers focused on one path in the home, relatively straight and not obstructed by furniture, and limited the measurements to a certain amount of time. People who spent more time at home during the COVID-19 pandemic did not skew the results, according to Dr. Korzenik, who added that it wasn’t total time walking around but a snippet in time.
A variety of sleep, breathing, and mobility metrics extracted by the device were integrated to assess disease activity. Investigators noted that during flares, sleep quality decreased, and more nocturnal awakenings occurred. They also found that gait speed slowed, and respiratory rate increased with flares.
When the investigators looked at sleep as a function of disease activity in the patient-reported surveys, they found a significant difference between people in remission and those with active disease. For example, people with active disease had a greater number of awakenings at night (P = .0016), less REM sleep at night (P = .0000), and less time in deep sleep (P = .000) compared with those in remission.
The technology “can identify flares with a predictive value that approaches fecal calprotectin,” Dr. Korzenik said.
Machine learning was used to look at severity of disease vs. fecal calprotectin values and “showed the data could be used as a marker of disease,” he added.
Use of a remote monitor, the comparison of validated vs. conventional data, and the large dataset were among the strengths of the study. The single-center design and exclusion of people with some comorbidities are potential limitations.
Further studies are warranted to confirm these findings and guide optimal care of people with Crohn’s disease, the investigators noted.
Earlier detection, earlier intervention
“The study is really important,” said session comoderator Raymond K. Cross Jr., MD, professor of medicine and director of the IBD program at the University of Maryland, Baltimore.
Monitoring devices like this “could be very useful,” Dr. Cross said. “It is not invasive, unless you consider a device in your house invasive. But, to me, I don’t think a box in my bedroom would be unnerving to me.”
Dr. Cross shared a couple of caveats. “The one devil in the details is always going to be cost,” he said. Also, it’s unclear who will read and interpret all the data generated by the device among “providers who are already overwhelmed with the volume of information.”
Moving forward, a device like this could offer multiple uses, Dr. Cross noted. If the device can detect relapses earlier, physicians could intervene sooner, he said. Also, the device could potentially flag people who are not taking their medications as recommended, or it could be used as a guide to optimize treatment response.
Whether data from the device could indicate when it’s appropriate to reduce the frequency or dose of medication or even when to withdraw therapy would be “really aspirational,” Dr. Cross added.
The study was funded by The Leona M. and Harry B. Helmsley Charitable Trust. Dr. Korzenik and Dr. Cross report no relevant financial relationships.
DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).
A version of this article first appeared on Medscape.com.
AT DDW 2023
Fewer discontinuations with infliximab vs. vedolizumab for UC maintenance therapy
CHICAGO – an updated meta-analysis of randomized clinical trials reveals.
At 1 year, 2% of people taking the anti–tumor necrosis factor (TNF) agent infliximab discontinued for lack of efficacy, compared with 24% of patients taking vedolizumab (Entyvio), an integrin receptor antagonist.
The safety profile of each agent is also important.
“We know that vedolizumab has less safety risks than an anti-TNF agent, but we also have the gut feeling that the anti-TNF agents are more efficacious,” lead author Marc Ferrante, MD, said in an interview.
“Of course, I don’t think we can really say that vedolizumab is the safest and infliximab is not safe, but there is some difference,” added Dr. Ferrante, a professor in the department of gastroenterology and hepatology, University Hospitals Leuven (Belgium).
The study was presented as a poster at the annual Digestive Disease Week (DDW).
The researchers conducted a pooled analysis of six randomized controlled trials from the past 10 years. They analyzed the NOR-SWITCH IV Q8W, the NCT02883452 SC Q2W, and LIBERTY-UC SC Q2W studies for infliximab, and the VISIBLE 1 SC Q2W, GEMINI 1 IV Q4W, and VARSITY IV Q8W trials for vedolizumab.
Their work expands on a meta-analysis by Dr. Ferrante and colleagues presented at DDW 2022. They added the 1-year results from the phase 3 LIBERTY-UC study to increase the number of participants taking infliximab or an infliximab biosimilar.
“Luckily, the results are very similar,” Dr. Ferrante said, and noted that they support previous findings that discontinuation of infliximab was lower than that of vedolizumab.
Most of the patients in the infliximab group were taking an infliximab biosimilar, whereas the vedolizumab group received the originator. Dr. Ferrante noted that the economic considerations involved in deciding between a biosimilar and an originator were not part of the research but that “there will be a difference in costs.”
Same mechanism, different route
The novel finding from the study includes the subcutaneous form of infliximab, which is not yet available in the United States, noted Joshua M. Steinberg, MD, director of inflammatory bowel disease at Gastroenterology of the Rockies, Denver, when asked to comment on the study. Currently, intravenously administered infliximab and vedolizumab are available in the United States.
A better comparator in the future would be looking at subcutaneous forms of both agents, especially “with the impending launch of subcutaneous vedolizumab in the United States,” said Dr. Steinberg, who is also a clinical instructor of medicine at the University of Colorado at Denver, Aurora.
He added that it’s reassuring overall that with a newer mode of administration but same mechanism of action, it is still feasible and durable for at least 1 year.
“The general consensus is that in terms of our biologics, vedolizumab is the safest because of its targeted mechanism of action. But sometimes the ‘safest choice’ isn’t the best choice,” Dr. Steinberg said. “I think in the right patient, the most effective treatment is going to be the one that works the best, and that’s not going to be universal.”
The study was sponsored by Celltrion, which makes an infliximab biosimilar. Dr. Ferrante receives honoraria as a consultant and speaker for Celltrion. Dr. Steinberg reported no relevant financial relationships.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
A version of this article first appeared on Medscape.com.
CHICAGO – an updated meta-analysis of randomized clinical trials reveals.
At 1 year, 2% of people taking the anti–tumor necrosis factor (TNF) agent infliximab discontinued for lack of efficacy, compared with 24% of patients taking vedolizumab (Entyvio), an integrin receptor antagonist.
The safety profile of each agent is also important.
“We know that vedolizumab has less safety risks than an anti-TNF agent, but we also have the gut feeling that the anti-TNF agents are more efficacious,” lead author Marc Ferrante, MD, said in an interview.
“Of course, I don’t think we can really say that vedolizumab is the safest and infliximab is not safe, but there is some difference,” added Dr. Ferrante, a professor in the department of gastroenterology and hepatology, University Hospitals Leuven (Belgium).
The study was presented as a poster at the annual Digestive Disease Week (DDW).
The researchers conducted a pooled analysis of six randomized controlled trials from the past 10 years. They analyzed the NOR-SWITCH IV Q8W, the NCT02883452 SC Q2W, and LIBERTY-UC SC Q2W studies for infliximab, and the VISIBLE 1 SC Q2W, GEMINI 1 IV Q4W, and VARSITY IV Q8W trials for vedolizumab.
Their work expands on a meta-analysis by Dr. Ferrante and colleagues presented at DDW 2022. They added the 1-year results from the phase 3 LIBERTY-UC study to increase the number of participants taking infliximab or an infliximab biosimilar.
“Luckily, the results are very similar,” Dr. Ferrante said, and noted that they support previous findings that discontinuation of infliximab was lower than that of vedolizumab.
Most of the patients in the infliximab group were taking an infliximab biosimilar, whereas the vedolizumab group received the originator. Dr. Ferrante noted that the economic considerations involved in deciding between a biosimilar and an originator were not part of the research but that “there will be a difference in costs.”
Same mechanism, different route
The novel finding from the study includes the subcutaneous form of infliximab, which is not yet available in the United States, noted Joshua M. Steinberg, MD, director of inflammatory bowel disease at Gastroenterology of the Rockies, Denver, when asked to comment on the study. Currently, intravenously administered infliximab and vedolizumab are available in the United States.
A better comparator in the future would be looking at subcutaneous forms of both agents, especially “with the impending launch of subcutaneous vedolizumab in the United States,” said Dr. Steinberg, who is also a clinical instructor of medicine at the University of Colorado at Denver, Aurora.
He added that it’s reassuring overall that with a newer mode of administration but same mechanism of action, it is still feasible and durable for at least 1 year.
“The general consensus is that in terms of our biologics, vedolizumab is the safest because of its targeted mechanism of action. But sometimes the ‘safest choice’ isn’t the best choice,” Dr. Steinberg said. “I think in the right patient, the most effective treatment is going to be the one that works the best, and that’s not going to be universal.”
The study was sponsored by Celltrion, which makes an infliximab biosimilar. Dr. Ferrante receives honoraria as a consultant and speaker for Celltrion. Dr. Steinberg reported no relevant financial relationships.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
A version of this article first appeared on Medscape.com.
CHICAGO – an updated meta-analysis of randomized clinical trials reveals.
At 1 year, 2% of people taking the anti–tumor necrosis factor (TNF) agent infliximab discontinued for lack of efficacy, compared with 24% of patients taking vedolizumab (Entyvio), an integrin receptor antagonist.
The safety profile of each agent is also important.
“We know that vedolizumab has less safety risks than an anti-TNF agent, but we also have the gut feeling that the anti-TNF agents are more efficacious,” lead author Marc Ferrante, MD, said in an interview.
“Of course, I don’t think we can really say that vedolizumab is the safest and infliximab is not safe, but there is some difference,” added Dr. Ferrante, a professor in the department of gastroenterology and hepatology, University Hospitals Leuven (Belgium).
The study was presented as a poster at the annual Digestive Disease Week (DDW).
The researchers conducted a pooled analysis of six randomized controlled trials from the past 10 years. They analyzed the NOR-SWITCH IV Q8W, the NCT02883452 SC Q2W, and LIBERTY-UC SC Q2W studies for infliximab, and the VISIBLE 1 SC Q2W, GEMINI 1 IV Q4W, and VARSITY IV Q8W trials for vedolizumab.
Their work expands on a meta-analysis by Dr. Ferrante and colleagues presented at DDW 2022. They added the 1-year results from the phase 3 LIBERTY-UC study to increase the number of participants taking infliximab or an infliximab biosimilar.
“Luckily, the results are very similar,” Dr. Ferrante said, and noted that they support previous findings that discontinuation of infliximab was lower than that of vedolizumab.
Most of the patients in the infliximab group were taking an infliximab biosimilar, whereas the vedolizumab group received the originator. Dr. Ferrante noted that the economic considerations involved in deciding between a biosimilar and an originator were not part of the research but that “there will be a difference in costs.”
Same mechanism, different route
The novel finding from the study includes the subcutaneous form of infliximab, which is not yet available in the United States, noted Joshua M. Steinberg, MD, director of inflammatory bowel disease at Gastroenterology of the Rockies, Denver, when asked to comment on the study. Currently, intravenously administered infliximab and vedolizumab are available in the United States.
A better comparator in the future would be looking at subcutaneous forms of both agents, especially “with the impending launch of subcutaneous vedolizumab in the United States,” said Dr. Steinberg, who is also a clinical instructor of medicine at the University of Colorado at Denver, Aurora.
He added that it’s reassuring overall that with a newer mode of administration but same mechanism of action, it is still feasible and durable for at least 1 year.
“The general consensus is that in terms of our biologics, vedolizumab is the safest because of its targeted mechanism of action. But sometimes the ‘safest choice’ isn’t the best choice,” Dr. Steinberg said. “I think in the right patient, the most effective treatment is going to be the one that works the best, and that’s not going to be universal.”
The study was sponsored by Celltrion, which makes an infliximab biosimilar. Dr. Ferrante receives honoraria as a consultant and speaker for Celltrion. Dr. Steinberg reported no relevant financial relationships.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
A version of this article first appeared on Medscape.com.
AT DDW 2023
BMI has greater impact on survival in younger breast cancer patients
new data suggest.
Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.
Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.
The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.
Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (30 kg/m2 or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.
DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).
“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.
In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.
The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.
In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.
When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
Data draw attention to quality of life and lifestyle factors
The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.
Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.
Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.
“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.
The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.
new data suggest.
Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.
Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.
The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.
Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (30 kg/m2 or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.
DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).
“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.
In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.
The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.
In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.
When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
Data draw attention to quality of life and lifestyle factors
The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.
Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.
Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.
“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.
The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.
new data suggest.
Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.
Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.
The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.
Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (30 kg/m2 or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.
DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).
“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.
In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.
The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.
In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.
When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
Data draw attention to quality of life and lifestyle factors
The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.
Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.
Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.
“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.
The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.
FROM ESMO BREAST CANCER 2023
Endoscopic sleeve gastroplasty plus obesity drugs add up to more weight loss
CHICAGO – Antiobesity medications and endoscopic sleeve gastroplasty (ESG) are popular strategies for weight loss on their own. Now researchers are looking at what happens when you combine them.
In a study presented at the annual Digestive Disease Week® (DDW), they found
Starting medication within 6 months of ESG was more ideal than other timing intervals. Initiating medical therapy more than 6 months before ESG was associated with less weight loss.
In the single-center, retrospective study, 224 patients were enrolled, of whom 34% were on monotherapy (ESG alone), 31% had combination therapy (medication prescribed within 6 months prior to or after ESG), and 35% had sequential therapy (medication more than 6 months prior to or after ESG).
Most patients were female, ranging from 74% to 95% of each group, and baseline BMI ranged from a mean 37.5 kg/m2 to 40.1 kg/m2.
The medications involved in the study were phentermine, phentermine/topiramate extended release (Qsymia), orlistat (Xenical, Alli), bupropion/naltrexone ER (Contrave), or the glucagonlike peptide–1 receptor agonist (GLP-1RA) liraglutide (Saxenda, Victoza) or semaglutide (Ozempic, Wegovy, Rybelsus). Of the patients who underwent combination therapy, 30% were prescribed a regimen that included a GLP-1RA. Of the patients who underwent sequential therapy, 81% were prescribed a medication first and 19% underwent ESG first.
At 1 year, the greatest total weight loss was a mean 23.7% with the combination of ESG and a GLP-1RA. Total weight loss was 18% with ESG plus a non–GLP-1RA medication. ESG alone led to 17.3%. Sequential therapy that began with ESG yielded 14.7% total weight loss, whereas sequential therapy that began with medication first resulted in 12% weight loss.
It’s possible that gastroplasty performed second was less impressive because the medications were very effective, and there was not as much weight to lose, said Pichamol Jirapinyo, MD, MPH, a bariatric endoscopist at Brigham and Women’s Hospital, Boston, and lead author of the study.
Researchers stopped medication therapy if people did not experience at least 5% total weight loss after 3 months on a maintenance dose.
Waiting for weight loss to start to plateau after gastroplasty might be an ideal time to add weight loss medication, said Dr. Jirapinyo. “Usually when I see them at 3 months, I plot how fast their weight loss has been. If it’s been going down [steadily], we do not offer an antiobesity medication until I see them again at 6 months.”
The serious adverse event (SAE) rate associated with ESG was similar among the three cohorts: 2.6% with monotherapy group, 1.4% with combination therapy, and 1.3% with sequential therapy. SAEs associated with antiobesity medication occurred in 1.3% of the sequential therapy group and was not reported in either of the other two groups.
“I certainly think combination therapy should be more effective than just gastroplasty alone and is probably better,” said Gregory L. Austin, MD, session comoderator and a gastroenterologist at the UCHealth Digestive Health Center, Denver.
“Whether you start immediately or wait 3 months afterwards is a question that still needs to be answered,” he added.
Dr. Austin agreed that taking an antiobesity medicine more than 6 months before gastroplasty might be associated with enough weight loss to make the gastroplasty look less effective.
He also noted that the study “doesn’t really address the question of whether you should offer gastroplasty to somebody who’s been on [medication] for more than 6 months because you probably still should if they haven’t achieved an appropriate weight loss that’s associated with reduced comorbidity risk going forward.”
Different study, similar result
In a second study, also presented at DDW 2023, investigators looked at timing of liraglutide for weight loss in a randomized controlled trial. They found that administration of GLP-1RA right after transoral outlet reduction endoscopy (TORe) in people with a history of Roux-en-Y gastric bypass extended weight loss longer than a placebo injection. This strategy was also favorable versus waiting to give liraglutide 1 year later.
The researchers randomly assigned 51 people to get weekly subcutaneous liraglutide injections following TORe for 12 months, then placebo injections for 12 months. They assigned 58 patients to receive weekly placebo injections following TORe for 12 months, then liraglutide injections for 12 months.
At 12 months following the procedure, total body weight loss (TBWL) among participants receiving liraglutide was about 22%, compared with about 14% among patients receiving placebo. At 24 months following the procedure (12 months after crossover), TBWL among patients in the liraglutide-first group was almost 35%, compared with about 24% in the placebo-first/liraglutide-second group.
There was a durable effect associated with liraglutide even after switching to placebo, said Ali Lahooti, lead study author and second-year medical student at Weill Cornell Medicine, New York.
“There did seem to be a better benefit of starting on it for the first year and then stopping it,” Dr. Austin noted.
These two studies come at a time when the debate over the timing of different obesity interventions continues. Some experts believe weight loss medications can help with the rebound in weight that some people experience months after bariatric surgery, for example.
‘Wave of the future’
The study by Dr. Jirapinyo and colleagues is “really exciting and interesting,” said Linda S. Lee, MD, medical director of endoscopy, Brigham and Women’s Hospital, Boston, when asked to comment.
Medication begun within 6 months of the endoscopic procedure “led to superior outcomes, compared to just endoscopy alone,” Dr. Lee said. “I think that’s really the wave of the future as far as treating patients with obesity issues. We clearly know that diet and exercise alone for most people is not good enough. Of course, we have surgery, but we also realize that with surgery sometimes the weight starts to creep back up over time.”
Dr. Lee noted that the study was limited because it was retrospective. Ideally, it would be good if future, prospective research randomly assigns people to endoscopy alone or endoscopy plus medication.
Dr. Lee also noted there is a limited number of bariatric endoscopists. By the time people with obesity get to a specialist, they’ve likely tried diet and exercise and “probably have seen all the commercials for these different medications. I think the reality is that most people will ask their primary care physicians about antiobesity medication.
“From my point of view, as long as the medicine is safe and not harming them, then let’s do both of them together,” Dr. Lee added.
Dr. Lee also mentioned another study (Abstract Mo1898) presented at DDW 2023 that showed total weight loss with endoscopic sleeve gastroplasty was durable over 10 years. Follow-up was with only seven patients, however.
Larger numbers are needed to confirm the finding, but it’s “exciting,” she said.
Dr. Jirapinyo receives grant/research support from Apollo Endosurgery, Fractyl, and USGI Medical, and is a consultant for ERBE, GI Dynamics, and Spatz Medical. Dr. Lahooti, Dr. Austin, and Dr. Lee reported no relevant financial relationships.
The meeting is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.
A version of this article first appeared on Medscape.com.
CHICAGO – Antiobesity medications and endoscopic sleeve gastroplasty (ESG) are popular strategies for weight loss on their own. Now researchers are looking at what happens when you combine them.
In a study presented at the annual Digestive Disease Week® (DDW), they found
Starting medication within 6 months of ESG was more ideal than other timing intervals. Initiating medical therapy more than 6 months before ESG was associated with less weight loss.
In the single-center, retrospective study, 224 patients were enrolled, of whom 34% were on monotherapy (ESG alone), 31% had combination therapy (medication prescribed within 6 months prior to or after ESG), and 35% had sequential therapy (medication more than 6 months prior to or after ESG).
Most patients were female, ranging from 74% to 95% of each group, and baseline BMI ranged from a mean 37.5 kg/m2 to 40.1 kg/m2.
The medications involved in the study were phentermine, phentermine/topiramate extended release (Qsymia), orlistat (Xenical, Alli), bupropion/naltrexone ER (Contrave), or the glucagonlike peptide–1 receptor agonist (GLP-1RA) liraglutide (Saxenda, Victoza) or semaglutide (Ozempic, Wegovy, Rybelsus). Of the patients who underwent combination therapy, 30% were prescribed a regimen that included a GLP-1RA. Of the patients who underwent sequential therapy, 81% were prescribed a medication first and 19% underwent ESG first.
At 1 year, the greatest total weight loss was a mean 23.7% with the combination of ESG and a GLP-1RA. Total weight loss was 18% with ESG plus a non–GLP-1RA medication. ESG alone led to 17.3%. Sequential therapy that began with ESG yielded 14.7% total weight loss, whereas sequential therapy that began with medication first resulted in 12% weight loss.
It’s possible that gastroplasty performed second was less impressive because the medications were very effective, and there was not as much weight to lose, said Pichamol Jirapinyo, MD, MPH, a bariatric endoscopist at Brigham and Women’s Hospital, Boston, and lead author of the study.
Researchers stopped medication therapy if people did not experience at least 5% total weight loss after 3 months on a maintenance dose.
Waiting for weight loss to start to plateau after gastroplasty might be an ideal time to add weight loss medication, said Dr. Jirapinyo. “Usually when I see them at 3 months, I plot how fast their weight loss has been. If it’s been going down [steadily], we do not offer an antiobesity medication until I see them again at 6 months.”
The serious adverse event (SAE) rate associated with ESG was similar among the three cohorts: 2.6% with monotherapy group, 1.4% with combination therapy, and 1.3% with sequential therapy. SAEs associated with antiobesity medication occurred in 1.3% of the sequential therapy group and was not reported in either of the other two groups.
“I certainly think combination therapy should be more effective than just gastroplasty alone and is probably better,” said Gregory L. Austin, MD, session comoderator and a gastroenterologist at the UCHealth Digestive Health Center, Denver.
“Whether you start immediately or wait 3 months afterwards is a question that still needs to be answered,” he added.
Dr. Austin agreed that taking an antiobesity medicine more than 6 months before gastroplasty might be associated with enough weight loss to make the gastroplasty look less effective.
He also noted that the study “doesn’t really address the question of whether you should offer gastroplasty to somebody who’s been on [medication] for more than 6 months because you probably still should if they haven’t achieved an appropriate weight loss that’s associated with reduced comorbidity risk going forward.”
Different study, similar result
In a second study, also presented at DDW 2023, investigators looked at timing of liraglutide for weight loss in a randomized controlled trial. They found that administration of GLP-1RA right after transoral outlet reduction endoscopy (TORe) in people with a history of Roux-en-Y gastric bypass extended weight loss longer than a placebo injection. This strategy was also favorable versus waiting to give liraglutide 1 year later.
The researchers randomly assigned 51 people to get weekly subcutaneous liraglutide injections following TORe for 12 months, then placebo injections for 12 months. They assigned 58 patients to receive weekly placebo injections following TORe for 12 months, then liraglutide injections for 12 months.
At 12 months following the procedure, total body weight loss (TBWL) among participants receiving liraglutide was about 22%, compared with about 14% among patients receiving placebo. At 24 months following the procedure (12 months after crossover), TBWL among patients in the liraglutide-first group was almost 35%, compared with about 24% in the placebo-first/liraglutide-second group.
There was a durable effect associated with liraglutide even after switching to placebo, said Ali Lahooti, lead study author and second-year medical student at Weill Cornell Medicine, New York.
“There did seem to be a better benefit of starting on it for the first year and then stopping it,” Dr. Austin noted.
These two studies come at a time when the debate over the timing of different obesity interventions continues. Some experts believe weight loss medications can help with the rebound in weight that some people experience months after bariatric surgery, for example.
‘Wave of the future’
The study by Dr. Jirapinyo and colleagues is “really exciting and interesting,” said Linda S. Lee, MD, medical director of endoscopy, Brigham and Women’s Hospital, Boston, when asked to comment.
Medication begun within 6 months of the endoscopic procedure “led to superior outcomes, compared to just endoscopy alone,” Dr. Lee said. “I think that’s really the wave of the future as far as treating patients with obesity issues. We clearly know that diet and exercise alone for most people is not good enough. Of course, we have surgery, but we also realize that with surgery sometimes the weight starts to creep back up over time.”
Dr. Lee noted that the study was limited because it was retrospective. Ideally, it would be good if future, prospective research randomly assigns people to endoscopy alone or endoscopy plus medication.
Dr. Lee also noted there is a limited number of bariatric endoscopists. By the time people with obesity get to a specialist, they’ve likely tried diet and exercise and “probably have seen all the commercials for these different medications. I think the reality is that most people will ask their primary care physicians about antiobesity medication.
“From my point of view, as long as the medicine is safe and not harming them, then let’s do both of them together,” Dr. Lee added.
Dr. Lee also mentioned another study (Abstract Mo1898) presented at DDW 2023 that showed total weight loss with endoscopic sleeve gastroplasty was durable over 10 years. Follow-up was with only seven patients, however.
Larger numbers are needed to confirm the finding, but it’s “exciting,” she said.
Dr. Jirapinyo receives grant/research support from Apollo Endosurgery, Fractyl, and USGI Medical, and is a consultant for ERBE, GI Dynamics, and Spatz Medical. Dr. Lahooti, Dr. Austin, and Dr. Lee reported no relevant financial relationships.
The meeting is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.
A version of this article first appeared on Medscape.com.
CHICAGO – Antiobesity medications and endoscopic sleeve gastroplasty (ESG) are popular strategies for weight loss on their own. Now researchers are looking at what happens when you combine them.
In a study presented at the annual Digestive Disease Week® (DDW), they found
Starting medication within 6 months of ESG was more ideal than other timing intervals. Initiating medical therapy more than 6 months before ESG was associated with less weight loss.
In the single-center, retrospective study, 224 patients were enrolled, of whom 34% were on monotherapy (ESG alone), 31% had combination therapy (medication prescribed within 6 months prior to or after ESG), and 35% had sequential therapy (medication more than 6 months prior to or after ESG).
Most patients were female, ranging from 74% to 95% of each group, and baseline BMI ranged from a mean 37.5 kg/m2 to 40.1 kg/m2.
The medications involved in the study were phentermine, phentermine/topiramate extended release (Qsymia), orlistat (Xenical, Alli), bupropion/naltrexone ER (Contrave), or the glucagonlike peptide–1 receptor agonist (GLP-1RA) liraglutide (Saxenda, Victoza) or semaglutide (Ozempic, Wegovy, Rybelsus). Of the patients who underwent combination therapy, 30% were prescribed a regimen that included a GLP-1RA. Of the patients who underwent sequential therapy, 81% were prescribed a medication first and 19% underwent ESG first.
At 1 year, the greatest total weight loss was a mean 23.7% with the combination of ESG and a GLP-1RA. Total weight loss was 18% with ESG plus a non–GLP-1RA medication. ESG alone led to 17.3%. Sequential therapy that began with ESG yielded 14.7% total weight loss, whereas sequential therapy that began with medication first resulted in 12% weight loss.
It’s possible that gastroplasty performed second was less impressive because the medications were very effective, and there was not as much weight to lose, said Pichamol Jirapinyo, MD, MPH, a bariatric endoscopist at Brigham and Women’s Hospital, Boston, and lead author of the study.
Researchers stopped medication therapy if people did not experience at least 5% total weight loss after 3 months on a maintenance dose.
Waiting for weight loss to start to plateau after gastroplasty might be an ideal time to add weight loss medication, said Dr. Jirapinyo. “Usually when I see them at 3 months, I plot how fast their weight loss has been. If it’s been going down [steadily], we do not offer an antiobesity medication until I see them again at 6 months.”
The serious adverse event (SAE) rate associated with ESG was similar among the three cohorts: 2.6% with monotherapy group, 1.4% with combination therapy, and 1.3% with sequential therapy. SAEs associated with antiobesity medication occurred in 1.3% of the sequential therapy group and was not reported in either of the other two groups.
“I certainly think combination therapy should be more effective than just gastroplasty alone and is probably better,” said Gregory L. Austin, MD, session comoderator and a gastroenterologist at the UCHealth Digestive Health Center, Denver.
“Whether you start immediately or wait 3 months afterwards is a question that still needs to be answered,” he added.
Dr. Austin agreed that taking an antiobesity medicine more than 6 months before gastroplasty might be associated with enough weight loss to make the gastroplasty look less effective.
He also noted that the study “doesn’t really address the question of whether you should offer gastroplasty to somebody who’s been on [medication] for more than 6 months because you probably still should if they haven’t achieved an appropriate weight loss that’s associated with reduced comorbidity risk going forward.”
Different study, similar result
In a second study, also presented at DDW 2023, investigators looked at timing of liraglutide for weight loss in a randomized controlled trial. They found that administration of GLP-1RA right after transoral outlet reduction endoscopy (TORe) in people with a history of Roux-en-Y gastric bypass extended weight loss longer than a placebo injection. This strategy was also favorable versus waiting to give liraglutide 1 year later.
The researchers randomly assigned 51 people to get weekly subcutaneous liraglutide injections following TORe for 12 months, then placebo injections for 12 months. They assigned 58 patients to receive weekly placebo injections following TORe for 12 months, then liraglutide injections for 12 months.
At 12 months following the procedure, total body weight loss (TBWL) among participants receiving liraglutide was about 22%, compared with about 14% among patients receiving placebo. At 24 months following the procedure (12 months after crossover), TBWL among patients in the liraglutide-first group was almost 35%, compared with about 24% in the placebo-first/liraglutide-second group.
There was a durable effect associated with liraglutide even after switching to placebo, said Ali Lahooti, lead study author and second-year medical student at Weill Cornell Medicine, New York.
“There did seem to be a better benefit of starting on it for the first year and then stopping it,” Dr. Austin noted.
These two studies come at a time when the debate over the timing of different obesity interventions continues. Some experts believe weight loss medications can help with the rebound in weight that some people experience months after bariatric surgery, for example.
‘Wave of the future’
The study by Dr. Jirapinyo and colleagues is “really exciting and interesting,” said Linda S. Lee, MD, medical director of endoscopy, Brigham and Women’s Hospital, Boston, when asked to comment.
Medication begun within 6 months of the endoscopic procedure “led to superior outcomes, compared to just endoscopy alone,” Dr. Lee said. “I think that’s really the wave of the future as far as treating patients with obesity issues. We clearly know that diet and exercise alone for most people is not good enough. Of course, we have surgery, but we also realize that with surgery sometimes the weight starts to creep back up over time.”
Dr. Lee noted that the study was limited because it was retrospective. Ideally, it would be good if future, prospective research randomly assigns people to endoscopy alone or endoscopy plus medication.
Dr. Lee also noted there is a limited number of bariatric endoscopists. By the time people with obesity get to a specialist, they’ve likely tried diet and exercise and “probably have seen all the commercials for these different medications. I think the reality is that most people will ask their primary care physicians about antiobesity medication.
“From my point of view, as long as the medicine is safe and not harming them, then let’s do both of them together,” Dr. Lee added.
Dr. Lee also mentioned another study (Abstract Mo1898) presented at DDW 2023 that showed total weight loss with endoscopic sleeve gastroplasty was durable over 10 years. Follow-up was with only seven patients, however.
Larger numbers are needed to confirm the finding, but it’s “exciting,” she said.
Dr. Jirapinyo receives grant/research support from Apollo Endosurgery, Fractyl, and USGI Medical, and is a consultant for ERBE, GI Dynamics, and Spatz Medical. Dr. Lahooti, Dr. Austin, and Dr. Lee reported no relevant financial relationships.
The meeting is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.
A version of this article first appeared on Medscape.com.
AT DDW 2023