Key clinical point: In patients with migraine, greater severity of photophobia is significantly associated with worse sleep-related outcomes, such as sleep quality (SQ), sleep disturbance (SDi), sleep onset latency (SOL), sleep-related impairment (SRI), and insomnia.

Major finding: Compared with patients with migraine and without photophobia, those with migraine and photophobia presented significantly poorer SQ (β 0.15; P < .001), longer SOL (β 0.10; P = .011), higher levels of SDi (β 0.12; P < .001) and SRI (β 0.08; P = .020), and a higher prevalence of insomnia (β 0.11; P = .005).

Study details: This cross-sectional observational study evaluated the association between photophobia and sleep-related outcomes in 852 patients with migraine using data from the American Registry for Migraine Research.

Disclosures: This study did not receive any specific funding. Some authors declared receiving compensation for consulting from, serving as consultants for, or having other ties with various sources.

Source: Sharp N, Burish MJ, Digre KB, et al. Photophobia is associated with lower sleep quality in individuals with migraine: Results from the American Registry for Migraine Research (ARMR). J Headache Pain. 2024;25:55. doi: 10.1186/s10194-024-01756-9 Source

Key clinical point: In patients with migraine, greater severity of photophobia is significantly associated with worse sleep-related outcomes, such as sleep quality (SQ), sleep disturbance (SDi), sleep onset latency (SOL), sleep-related impairment (SRI), and insomnia.

Major finding: Compared with patients with migraine and without photophobia, those with migraine and photophobia presented significantly poorer SQ (β 0.15; P < .001), longer SOL (β 0.10; P = .011), higher levels of SDi (β 0.12; P < .001) and SRI (β 0.08; P = .020), and a higher prevalence of insomnia (β 0.11; P = .005).

Study details: This cross-sectional observational study evaluated the association between photophobia and sleep-related outcomes in 852 patients with migraine using data from the American Registry for Migraine Research.

Disclosures: This study did not receive any specific funding. Some authors declared receiving compensation for consulting from, serving as consultants for, or having other ties with various sources.

Source: Sharp N, Burish MJ, Digre KB, et al. Photophobia is associated with lower sleep quality in individuals with migraine: Results from the American Registry for Migraine Research (ARMR). J Headache Pain. 2024;25:55. doi: 10.1186/s10194-024-01756-9 Source

Key clinical point: In patients with migraine, greater severity of photophobia is significantly associated with worse sleep-related outcomes, such as sleep quality (SQ), sleep disturbance (SDi), sleep onset latency (SOL), sleep-related impairment (SRI), and insomnia.

Major finding: Compared with patients with migraine and without photophobia, those with migraine and photophobia presented significantly poorer SQ (β 0.15; P < .001), longer SOL (β 0.10; P = .011), higher levels of SDi (β 0.12; P < .001) and SRI (β 0.08; P = .020), and a higher prevalence of insomnia (β 0.11; P = .005).

Study details: This cross-sectional observational study evaluated the association between photophobia and sleep-related outcomes in 852 patients with migraine using data from the American Registry for Migraine Research.

Disclosures: This study did not receive any specific funding. Some authors declared receiving compensation for consulting from, serving as consultants for, or having other ties with various sources.

Source: Sharp N, Burish MJ, Digre KB, et al. Photophobia is associated with lower sleep quality in individuals with migraine: Results from the American Registry for Migraine Research (ARMR). J Headache Pain. 2024;25:55. doi: 10.1186/s10194-024-01756-9 Source

Key clinical point: Patients with migraine had an increased risk for vascular dementia (VaD), with the risk being significantly higher in those with chronic vs episodic migraine.

Major finding: Compared with individuals without migraine, patients with migraine had a 1.21-fold higher risk for VaD (adjusted hazard ratio [aHR] 1.21; 95% CI 1.17-1.25), with the cumulative incidence of migraine being significantly higher in patients with chronic vs episodic migraine (log-rank P < .001).

Study details: This 10-year retrospective population-based cohort study included 212,836 patients with migraine and 5,863,348 participants without migraine, of whom 3914 (1.8%) and 60,259 (1.0%), respectively, were diagnosed with VaD during the follow-up period.

Disclosures: This study was funded by a grant from the National Research Foundation, Republic of Korea, and others. The authors declared no conflicts of interest.

Source: Shin H, Ha WS, Kim J, et al. Association between migraine and the risk of vascular dementia: A nationwide longitudinal study in South Korea. PLoS One. 2024;19:e0300379. doi: 10.1371/journal.pone.0300379 Source

Key clinical point: Patients with migraine had an increased risk for vascular dementia (VaD), with the risk being significantly higher in those with chronic vs episodic migraine.

Major finding: Compared with individuals without migraine, patients with migraine had a 1.21-fold higher risk for VaD (adjusted hazard ratio [aHR] 1.21; 95% CI 1.17-1.25), with the cumulative incidence of migraine being significantly higher in patients with chronic vs episodic migraine (log-rank P < .001).

Study details: This 10-year retrospective population-based cohort study included 212,836 patients with migraine and 5,863,348 participants without migraine, of whom 3914 (1.8%) and 60,259 (1.0%), respectively, were diagnosed with VaD during the follow-up period.

Disclosures: This study was funded by a grant from the National Research Foundation, Republic of Korea, and others. The authors declared no conflicts of interest.

Source: Shin H, Ha WS, Kim J, et al. Association between migraine and the risk of vascular dementia: A nationwide longitudinal study in South Korea. PLoS One. 2024;19:e0300379. doi: 10.1371/journal.pone.0300379 Source

Key clinical point: Patients with migraine had an increased risk for vascular dementia (VaD), with the risk being significantly higher in those with chronic vs episodic migraine.

Major finding: Compared with individuals without migraine, patients with migraine had a 1.21-fold higher risk for VaD (adjusted hazard ratio [aHR] 1.21; 95% CI 1.17-1.25), with the cumulative incidence of migraine being significantly higher in patients with chronic vs episodic migraine (log-rank P < .001).

Study details: This 10-year retrospective population-based cohort study included 212,836 patients with migraine and 5,863,348 participants without migraine, of whom 3914 (1.8%) and 60,259 (1.0%), respectively, were diagnosed with VaD during the follow-up period.

Disclosures: This study was funded by a grant from the National Research Foundation, Republic of Korea, and others. The authors declared no conflicts of interest.

Source: Shin H, Ha WS, Kim J, et al. Association between migraine and the risk of vascular dementia: A nationwide longitudinal study in South Korea. PLoS One. 2024;19:e0300379. doi: 10.1371/journal.pone.0300379 Source

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

TOPLINE: 

Individuals with overweight and obesity who reach a weight-loss plateau at around 6 months on a healthy weight-loss diet may not achieve further weight reduction after switching to a different weight-loss diet.

METHODOLOGY:

• Dietary and lifestyle interventions initially result in rapid weight loss, followed by a weight-loss plateau after a few months and weight regain within a year or two, and diet fatigue has been proposed as a cause but not studied.
• This secondary analysis of a randomized trial assessed weight-loss trajectories before and after switching from a healthy low-carbohydrate (LC) diet to a healthy low-fat (LF) diet (or vice versa) in individuals with overweight and obesity.
• Overall, 42 participants (mean age, 42 years; 64% women; 87% White individuals) recruited from a local community in Palo Alto, California, were assigned to the LF or LC diet for the first 6 months, after which they were switched to the other diet for the remaining 6 months.
• Data from the DIETFITS trial, wherein participants remained either on the LF or LC diet for 12 months, were used as historical control.

The primary outcome was percent weight change at 3-6 months vs that observed at 6-9 months.

TAKEAWAY:

• The combined average weight loss was 7% (95% CI, 8%-6%) during the first 3 months, declining to 2% (95% CI, 3%-1%) between 3 and 6 months. On switching diets, the weight loss further slowed to 1% (95% CI, 2%-0.4%) between 6 and 9 months, with a modest increase in weight of 0.6% (95% CI, −0.1% to 1.3%) between 9 and 12 months.
• By diet order, participants in the LF first arm did not plateau and experienced a similar weight loss from 6 to 9 months as they had experienced from 3 to 6 months (relative change, −0.1%; 95% CI, −1.5% to 1.3%), while the LC first arm essentially nullified the 3-6 month weight loss during the 6-9 month LF phase (relative change, 2.2%; 95% CI, 0.7%-3.6%).
• For the LC first arm, low-density lipoprotein increased at 3 months and decreased when the participants switched to LF at 6 months, whereas the opposite effect was seen for the transition from LF to LC. Triglyceride levels decreased in both intervention arms.
• Insulin levels decreased in both dietary intervention arms between baseline and 6 months and plateaued following the 6-month dietary switch.

IN PRACTICE:

“This suggests that the weight-loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet,” wrote the authors. “As a person transitions from a weight loss to weight maintenance phase, a shift in the approach used may be required.”

SOURCE:

The study, led by Matthew J. Landry, Stanford Prevention Research Center, School of Medicine, Stanford University, California, was published in Scientific Reports.

LIMITATIONS:

The study results showed some possible differential trends but also highlighted the small sample size and large variability. Participants may have been unable to provide accurate estimates of self-reported energy intake. The authors also acknowledged that regular physical activity may have contributed to the maintenance of weight loss observed in this study.

DISCLOSURES:

The study was supported by the Hass Avocado Board; Human Health Service grant (General Clinical Research Centers and National Center for Research Resources, National Institutes of Health); National Heart, Lung, and Blood Institute; and Stanford Diabetes Research Center. The authors declared no conflicts of interest.

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

TOPLINE: 

Individuals with overweight and obesity who reach a weight-loss plateau at around 6 months on a healthy weight-loss diet may not achieve further weight reduction after switching to a different weight-loss diet.

METHODOLOGY:

• Dietary and lifestyle interventions initially result in rapid weight loss, followed by a weight-loss plateau after a few months and weight regain within a year or two, and diet fatigue has been proposed as a cause but not studied.
• This secondary analysis of a randomized trial assessed weight-loss trajectories before and after switching from a healthy low-carbohydrate (LC) diet to a healthy low-fat (LF) diet (or vice versa) in individuals with overweight and obesity.
• Overall, 42 participants (mean age, 42 years; 64% women; 87% White individuals) recruited from a local community in Palo Alto, California, were assigned to the LF or LC diet for the first 6 months, after which they were switched to the other diet for the remaining 6 months.
• Data from the DIETFITS trial, wherein participants remained either on the LF or LC diet for 12 months, were used as historical control.

The primary outcome was percent weight change at 3-6 months vs that observed at 6-9 months.

TAKEAWAY:

• The combined average weight loss was 7% (95% CI, 8%-6%) during the first 3 months, declining to 2% (95% CI, 3%-1%) between 3 and 6 months. On switching diets, the weight loss further slowed to 1% (95% CI, 2%-0.4%) between 6 and 9 months, with a modest increase in weight of 0.6% (95% CI, −0.1% to 1.3%) between 9 and 12 months.
• By diet order, participants in the LF first arm did not plateau and experienced a similar weight loss from 6 to 9 months as they had experienced from 3 to 6 months (relative change, −0.1%; 95% CI, −1.5% to 1.3%), while the LC first arm essentially nullified the 3-6 month weight loss during the 6-9 month LF phase (relative change, 2.2%; 95% CI, 0.7%-3.6%).
• For the LC first arm, low-density lipoprotein increased at 3 months and decreased when the participants switched to LF at 6 months, whereas the opposite effect was seen for the transition from LF to LC. Triglyceride levels decreased in both intervention arms.
• Insulin levels decreased in both dietary intervention arms between baseline and 6 months and plateaued following the 6-month dietary switch.

IN PRACTICE:

“This suggests that the weight-loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet,” wrote the authors. “As a person transitions from a weight loss to weight maintenance phase, a shift in the approach used may be required.”

SOURCE:

The study, led by Matthew J. Landry, Stanford Prevention Research Center, School of Medicine, Stanford University, California, was published in Scientific Reports.

LIMITATIONS:

The study results showed some possible differential trends but also highlighted the small sample size and large variability. Participants may have been unable to provide accurate estimates of self-reported energy intake. The authors also acknowledged that regular physical activity may have contributed to the maintenance of weight loss observed in this study.

DISCLOSURES:

The study was supported by the Hass Avocado Board; Human Health Service grant (General Clinical Research Centers and National Center for Research Resources, National Institutes of Health); National Heart, Lung, and Blood Institute; and Stanford Diabetes Research Center. The authors declared no conflicts of interest.

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

TOPLINE: 

Individuals with overweight and obesity who reach a weight-loss plateau at around 6 months on a healthy weight-loss diet may not achieve further weight reduction after switching to a different weight-loss diet.

METHODOLOGY:

• Dietary and lifestyle interventions initially result in rapid weight loss, followed by a weight-loss plateau after a few months and weight regain within a year or two, and diet fatigue has been proposed as a cause but not studied.
• This secondary analysis of a randomized trial assessed weight-loss trajectories before and after switching from a healthy low-carbohydrate (LC) diet to a healthy low-fat (LF) diet (or vice versa) in individuals with overweight and obesity.
• Overall, 42 participants (mean age, 42 years; 64% women; 87% White individuals) recruited from a local community in Palo Alto, California, were assigned to the LF or LC diet for the first 6 months, after which they were switched to the other diet for the remaining 6 months.
• Data from the DIETFITS trial, wherein participants remained either on the LF or LC diet for 12 months, were used as historical control.

The primary outcome was percent weight change at 3-6 months vs that observed at 6-9 months.

TAKEAWAY:

• The combined average weight loss was 7% (95% CI, 8%-6%) during the first 3 months, declining to 2% (95% CI, 3%-1%) between 3 and 6 months. On switching diets, the weight loss further slowed to 1% (95% CI, 2%-0.4%) between 6 and 9 months, with a modest increase in weight of 0.6% (95% CI, −0.1% to 1.3%) between 9 and 12 months.
• By diet order, participants in the LF first arm did not plateau and experienced a similar weight loss from 6 to 9 months as they had experienced from 3 to 6 months (relative change, −0.1%; 95% CI, −1.5% to 1.3%), while the LC first arm essentially nullified the 3-6 month weight loss during the 6-9 month LF phase (relative change, 2.2%; 95% CI, 0.7%-3.6%).
• For the LC first arm, low-density lipoprotein increased at 3 months and decreased when the participants switched to LF at 6 months, whereas the opposite effect was seen for the transition from LF to LC. Triglyceride levels decreased in both intervention arms.
• Insulin levels decreased in both dietary intervention arms between baseline and 6 months and plateaued following the 6-month dietary switch.

IN PRACTICE:

“This suggests that the weight-loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet,” wrote the authors. “As a person transitions from a weight loss to weight maintenance phase, a shift in the approach used may be required.”

SOURCE:

The study, led by Matthew J. Landry, Stanford Prevention Research Center, School of Medicine, Stanford University, California, was published in Scientific Reports.

LIMITATIONS:

The study results showed some possible differential trends but also highlighted the small sample size and large variability. Participants may have been unable to provide accurate estimates of self-reported energy intake. The authors also acknowledged that regular physical activity may have contributed to the maintenance of weight loss observed in this study.

DISCLOSURES:

The study was supported by the Hass Avocado Board; Human Health Service grant (General Clinical Research Centers and National Center for Research Resources, National Institutes of Health); National Heart, Lung, and Blood Institute; and Stanford Diabetes Research Center. The authors declared no conflicts of interest.

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

NEW YORK — Psychiatric comorbidities are highly prevalent in patients with eating disorders (EDs), a large study showed.

In a propensity-matched cohort of young adults with and without EDs, a wide variety of psychiatric disorders including depression and anxiety, as well as cannabis and alcohol use disorders, were more common in those with EDs, investigators found.

Comorbid psychiatric disorders should be “top of mind when working with someone with an eating disorder. If you are able to treat the comorbid psychiatric conditions, they might have a better recovery from the eating disorder,” study investigator Angela Liu, MD, with Northwell Health at Zucker Hillside Hospital, Glen Oaks, New York, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

Data Gap

As previously reported by this news organization, more than one in five children worldwide are at risk for an ED and US medical admissions for adolescents with restrictive EDs more than doubled during the pandemic.

Yet there remains a “gap in the literature” about the prevalence of comorbid psychiatric conditions in people with EDs, specifically in young people, Dr. Liu explained.

“To our knowledge, this is the first study using a real-world, multistate administrative dataset to estimate the prevalence of psychiatric comorbidities in young people diagnosed with an eating disorder,” Dr. Liu said.

Using the TriNetX database, the researchers identified through ICD-10 codes 14,524 individuals with EDs (mean age, 15.9 years; 79% women) and 110,051 without EDs who were receiving antidepressants (mean age, 17.8 years; 65% women).

“There was a much higher prevalence of almost all other psychiatric conditions in those with an eating disorder compared to the general psychiatry population,” coinvestigator Binx Y. Lin, MD, MSc, with Virginia Tech Carilion School of Medicine in Roanoke, Virginia, told this news organization.

In the baseline comparison (before matching), psychiatric disorders seen more often in adults with than in those without EDs included (but were not limited to) mood disorders (51% vs 23%), generalized anxiety disorder (GAD; 30% vs 8%), posttraumatic stress disorder (PTSD; 10% vs 2%), obsessive-compulsive disorder (OCD; 8% vs 1%), panic disorder (6% vs 2%), substance use disorder (8% vs 5%), and adjustment disorders (5% vs 2%).

The results held after propensity score matching, with numerous psychiatric conditions significantly (P < .001) more prevalent in the ED cohort.

Understanding the burden of comorbid psychiatric disorders in young people with EDs is important to design comprehensive, evidence-based interventions, the researchers said.

Providing perspective on this topic, Petros Levounis, MD, professor and chair, Department of Psychiatry, Rutgers New Jersey Medical School, Newark, New Jersey, noted that “comorbidity between substance use disorders and other psychiatric disorders has both been grossly underestimated and grossly overestimated.

“I go around the country and see rehab programs, and there are people that very strongly believe that if you stop using the drugs, you won’t have problems with depression or anxiety or whatever,” Dr. Levounis, immediate past president of the APA, shared with this news organization.

“Others say they have never seen somebody who’s addicted to something that doesn’t also have some other psychiatric disorders and if you just scratch the surface, you always find some other psychological or psychiatric problem lying behind. Neither of them are true,” he cautioned.

Dr. Levounis said it’s important to recognize that “some people with addiction will also have another psychiatric disorder. But clearly there are people who just have a mental illness without addiction, and there are clearly people who will just have addiction without other mental illness.”

This research had no commercial funding and was supported in part by the American Psychiatric Association Research Fellowship. Dr. Liu, Dr. Lin, and Dr. Levounis had no relevant disclosures.

A version of this article appeared on Medscape.com .

NEW YORK — Psychiatric comorbidities are highly prevalent in patients with eating disorders (EDs), a large study showed.

In a propensity-matched cohort of young adults with and without EDs, a wide variety of psychiatric disorders including depression and anxiety, as well as cannabis and alcohol use disorders, were more common in those with EDs, investigators found.

Comorbid psychiatric disorders should be “top of mind when working with someone with an eating disorder. If you are able to treat the comorbid psychiatric conditions, they might have a better recovery from the eating disorder,” study investigator Angela Liu, MD, with Northwell Health at Zucker Hillside Hospital, Glen Oaks, New York, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

Data Gap

As previously reported by this news organization, more than one in five children worldwide are at risk for an ED and US medical admissions for adolescents with restrictive EDs more than doubled during the pandemic.

Yet there remains a “gap in the literature” about the prevalence of comorbid psychiatric conditions in people with EDs, specifically in young people, Dr. Liu explained.

“To our knowledge, this is the first study using a real-world, multistate administrative dataset to estimate the prevalence of psychiatric comorbidities in young people diagnosed with an eating disorder,” Dr. Liu said.

Using the TriNetX database, the researchers identified through ICD-10 codes 14,524 individuals with EDs (mean age, 15.9 years; 79% women) and 110,051 without EDs who were receiving antidepressants (mean age, 17.8 years; 65% women).

“There was a much higher prevalence of almost all other psychiatric conditions in those with an eating disorder compared to the general psychiatry population,” coinvestigator Binx Y. Lin, MD, MSc, with Virginia Tech Carilion School of Medicine in Roanoke, Virginia, told this news organization.

In the baseline comparison (before matching), psychiatric disorders seen more often in adults with than in those without EDs included (but were not limited to) mood disorders (51% vs 23%), generalized anxiety disorder (GAD; 30% vs 8%), posttraumatic stress disorder (PTSD; 10% vs 2%), obsessive-compulsive disorder (OCD; 8% vs 1%), panic disorder (6% vs 2%), substance use disorder (8% vs 5%), and adjustment disorders (5% vs 2%).

The results held after propensity score matching, with numerous psychiatric conditions significantly (P < .001) more prevalent in the ED cohort.

Understanding the burden of comorbid psychiatric disorders in young people with EDs is important to design comprehensive, evidence-based interventions, the researchers said.

Providing perspective on this topic, Petros Levounis, MD, professor and chair, Department of Psychiatry, Rutgers New Jersey Medical School, Newark, New Jersey, noted that “comorbidity between substance use disorders and other psychiatric disorders has both been grossly underestimated and grossly overestimated.

“I go around the country and see rehab programs, and there are people that very strongly believe that if you stop using the drugs, you won’t have problems with depression or anxiety or whatever,” Dr. Levounis, immediate past president of the APA, shared with this news organization.

“Others say they have never seen somebody who’s addicted to something that doesn’t also have some other psychiatric disorders and if you just scratch the surface, you always find some other psychological or psychiatric problem lying behind. Neither of them are true,” he cautioned.

Dr. Levounis said it’s important to recognize that “some people with addiction will also have another psychiatric disorder. But clearly there are people who just have a mental illness without addiction, and there are clearly people who will just have addiction without other mental illness.”

This research had no commercial funding and was supported in part by the American Psychiatric Association Research Fellowship. Dr. Liu, Dr. Lin, and Dr. Levounis had no relevant disclosures.

A version of this article appeared on Medscape.com .

NEW YORK — Psychiatric comorbidities are highly prevalent in patients with eating disorders (EDs), a large study showed.

In a propensity-matched cohort of young adults with and without EDs, a wide variety of psychiatric disorders including depression and anxiety, as well as cannabis and alcohol use disorders, were more common in those with EDs, investigators found.

Comorbid psychiatric disorders should be “top of mind when working with someone with an eating disorder. If you are able to treat the comorbid psychiatric conditions, they might have a better recovery from the eating disorder,” study investigator Angela Liu, MD, with Northwell Health at Zucker Hillside Hospital, Glen Oaks, New York, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

Data Gap

As previously reported by this news organization, more than one in five children worldwide are at risk for an ED and US medical admissions for adolescents with restrictive EDs more than doubled during the pandemic.

Yet there remains a “gap in the literature” about the prevalence of comorbid psychiatric conditions in people with EDs, specifically in young people, Dr. Liu explained.

“To our knowledge, this is the first study using a real-world, multistate administrative dataset to estimate the prevalence of psychiatric comorbidities in young people diagnosed with an eating disorder,” Dr. Liu said.

Using the TriNetX database, the researchers identified through ICD-10 codes 14,524 individuals with EDs (mean age, 15.9 years; 79% women) and 110,051 without EDs who were receiving antidepressants (mean age, 17.8 years; 65% women).

“There was a much higher prevalence of almost all other psychiatric conditions in those with an eating disorder compared to the general psychiatry population,” coinvestigator Binx Y. Lin, MD, MSc, with Virginia Tech Carilion School of Medicine in Roanoke, Virginia, told this news organization.

In the baseline comparison (before matching), psychiatric disorders seen more often in adults with than in those without EDs included (but were not limited to) mood disorders (51% vs 23%), generalized anxiety disorder (GAD; 30% vs 8%), posttraumatic stress disorder (PTSD; 10% vs 2%), obsessive-compulsive disorder (OCD; 8% vs 1%), panic disorder (6% vs 2%), substance use disorder (8% vs 5%), and adjustment disorders (5% vs 2%).

The results held after propensity score matching, with numerous psychiatric conditions significantly (P < .001) more prevalent in the ED cohort.

Understanding the burden of comorbid psychiatric disorders in young people with EDs is important to design comprehensive, evidence-based interventions, the researchers said.

Providing perspective on this topic, Petros Levounis, MD, professor and chair, Department of Psychiatry, Rutgers New Jersey Medical School, Newark, New Jersey, noted that “comorbidity between substance use disorders and other psychiatric disorders has both been grossly underestimated and grossly overestimated.

“I go around the country and see rehab programs, and there are people that very strongly believe that if you stop using the drugs, you won’t have problems with depression or anxiety or whatever,” Dr. Levounis, immediate past president of the APA, shared with this news organization.

“Others say they have never seen somebody who’s addicted to something that doesn’t also have some other psychiatric disorders and if you just scratch the surface, you always find some other psychological or psychiatric problem lying behind. Neither of them are true,” he cautioned.

Dr. Levounis said it’s important to recognize that “some people with addiction will also have another psychiatric disorder. But clearly there are people who just have a mental illness without addiction, and there are clearly people who will just have addiction without other mental illness.”

This research had no commercial funding and was supported in part by the American Psychiatric Association Research Fellowship. Dr. Liu, Dr. Lin, and Dr. Levounis had no relevant disclosures.

A version of this article appeared on Medscape.com .

WASHINGTON — Ablation of the gastric fundus to reduce production of the “hunger hormone” ghrelin resulted in decreased appetite and significant weight loss among participants in a small first-in-human trial.

“Patients reported a decrease in hunger, appetite, and cravings and an increase in control over [their] eating,” said senior study investigator Christopher McGowan, MD, AGAF, a gastroenterologist in private practice and medical director of True You Weight Loss in Cary, North Carolina.

Brian Strickland Photography

Major Findings

In the trial, 10 women (mean age, 38 years; mean body mass index, 40.2) underwent endoscopic fundic mucosal ablation via hybrid argon plasma coagulation in an ambulatory setting under general anesthesia from November 1, 2022, to April 14, 2023. The procedure took less than an hour on average, and the technique gave them easy access to the fundus, Dr. McGowan said.

Compared with baseline, there were multiple beneficial outcomes at 6 months:

• 45% less circulating ghrelin in the blood.
• 53% drop in ghrelin-producing cells in the fundus.
• 42% reduction in stomach capacity.
• 43% decrease in hunger, appetite, and cravings.
• 7.7% body weight loss.

Over the 6 months of the study, mean ghrelin concentrations dropped from 461.6 pg/mL at baseline to 254.8 pg/mL (P = .006).

It is fascinating that the hormone ghrelin decreased just by ablating, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024. “They used the same device that we use to treat bleeding ulcers or lesions in the stomach and applied it broadly over the whole upper part of the stomach.”

Another Anti-Obesity Tool?

“We’re all familiar with the epidemic that is obesity affecting nearly one in two adults, and the profound impact that it has on patients’ health, their quality of life, as well as the healthcare system,” Dr. McGowan said. “It’s clear that we need every tool possible to address this because we know that obesity is not a matter of willpower. It’s a disease.”

Gastric fundus ablation “may represent, and frankly should represent, a treatment option for the greater than 100 million US adults with obesity,” he added.

Not every patient wants to or can access GLP-1 medications, Dr. McGowan said. Also, “there’s a difference between taking a medication long-term, requiring an injection every week, vs a single intervention in time that carries forward.”

Ablation could also help people transition after they stop GLP-1 medications to help them maintain their weight loss, he said.

Weight loss is the endpoint you care about the most, said Dr. Laine, who co-moderated the press briefing.

Though the weight loss of 7.7% was not a large percentage, it was only 10 patients. We will have to see whether the total body weight loss is different when they do the procedure in more patients or if they can combine different mechanisms, Dr. Laine said.

It remains unclear whether gastric fundus ablation would be a stand-alone procedure or used in combination with another endoscopic weight-management intervention, bariatric surgery, or medication.

The endoscopic sleeve, which is a stomach-reducing procedure, is very effective, but it doesn’t diminish hunger, Dr. McGowan said. Combining it with ablation may be “a best-of-both-worlds scenario.”

Dr. Laine added that another open question is whether the gastric fundal accommodation will be associated with any side effects such as dyspepsia.

Dr. McGowan reported consulting for Boston Scientific and Apollo Endosurgery. Dr. Laine reported no relevant financial relationships.

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

WASHINGTON — Ablation of the gastric fundus to reduce production of the “hunger hormone” ghrelin resulted in decreased appetite and significant weight loss among participants in a small first-in-human trial.

“Patients reported a decrease in hunger, appetite, and cravings and an increase in control over [their] eating,” said senior study investigator Christopher McGowan, MD, AGAF, a gastroenterologist in private practice and medical director of True You Weight Loss in Cary, North Carolina.

Brian Strickland Photography

Major Findings

In the trial, 10 women (mean age, 38 years; mean body mass index, 40.2) underwent endoscopic fundic mucosal ablation via hybrid argon plasma coagulation in an ambulatory setting under general anesthesia from November 1, 2022, to April 14, 2023. The procedure took less than an hour on average, and the technique gave them easy access to the fundus, Dr. McGowan said.

Compared with baseline, there were multiple beneficial outcomes at 6 months:

• 45% less circulating ghrelin in the blood.
• 53% drop in ghrelin-producing cells in the fundus.
• 42% reduction in stomach capacity.
• 43% decrease in hunger, appetite, and cravings.
• 7.7% body weight loss.

Over the 6 months of the study, mean ghrelin concentrations dropped from 461.6 pg/mL at baseline to 254.8 pg/mL (P = .006).

It is fascinating that the hormone ghrelin decreased just by ablating, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024. “They used the same device that we use to treat bleeding ulcers or lesions in the stomach and applied it broadly over the whole upper part of the stomach.”

Another Anti-Obesity Tool?

“We’re all familiar with the epidemic that is obesity affecting nearly one in two adults, and the profound impact that it has on patients’ health, their quality of life, as well as the healthcare system,” Dr. McGowan said. “It’s clear that we need every tool possible to address this because we know that obesity is not a matter of willpower. It’s a disease.”

Gastric fundus ablation “may represent, and frankly should represent, a treatment option for the greater than 100 million US adults with obesity,” he added.

Not every patient wants to or can access GLP-1 medications, Dr. McGowan said. Also, “there’s a difference between taking a medication long-term, requiring an injection every week, vs a single intervention in time that carries forward.”

Ablation could also help people transition after they stop GLP-1 medications to help them maintain their weight loss, he said.

Weight loss is the endpoint you care about the most, said Dr. Laine, who co-moderated the press briefing.

Though the weight loss of 7.7% was not a large percentage, it was only 10 patients. We will have to see whether the total body weight loss is different when they do the procedure in more patients or if they can combine different mechanisms, Dr. Laine said.

It remains unclear whether gastric fundus ablation would be a stand-alone procedure or used in combination with another endoscopic weight-management intervention, bariatric surgery, or medication.

The endoscopic sleeve, which is a stomach-reducing procedure, is very effective, but it doesn’t diminish hunger, Dr. McGowan said. Combining it with ablation may be “a best-of-both-worlds scenario.”

Dr. Laine added that another open question is whether the gastric fundal accommodation will be associated with any side effects such as dyspepsia.

Dr. McGowan reported consulting for Boston Scientific and Apollo Endosurgery. Dr. Laine reported no relevant financial relationships.

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

WASHINGTON — Ablation of the gastric fundus to reduce production of the “hunger hormone” ghrelin resulted in decreased appetite and significant weight loss among participants in a small first-in-human trial.

“Patients reported a decrease in hunger, appetite, and cravings and an increase in control over [their] eating,” said senior study investigator Christopher McGowan, MD, AGAF, a gastroenterologist in private practice and medical director of True You Weight Loss in Cary, North Carolina.

Brian Strickland Photography

Major Findings

In the trial, 10 women (mean age, 38 years; mean body mass index, 40.2) underwent endoscopic fundic mucosal ablation via hybrid argon plasma coagulation in an ambulatory setting under general anesthesia from November 1, 2022, to April 14, 2023. The procedure took less than an hour on average, and the technique gave them easy access to the fundus, Dr. McGowan said.

Compared with baseline, there were multiple beneficial outcomes at 6 months:

• 45% less circulating ghrelin in the blood.
• 53% drop in ghrelin-producing cells in the fundus.
• 42% reduction in stomach capacity.
• 43% decrease in hunger, appetite, and cravings.
• 7.7% body weight loss.

Over the 6 months of the study, mean ghrelin concentrations dropped from 461.6 pg/mL at baseline to 254.8 pg/mL (P = .006).

It is fascinating that the hormone ghrelin decreased just by ablating, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024. “They used the same device that we use to treat bleeding ulcers or lesions in the stomach and applied it broadly over the whole upper part of the stomach.”

Another Anti-Obesity Tool?

“We’re all familiar with the epidemic that is obesity affecting nearly one in two adults, and the profound impact that it has on patients’ health, their quality of life, as well as the healthcare system,” Dr. McGowan said. “It’s clear that we need every tool possible to address this because we know that obesity is not a matter of willpower. It’s a disease.”

Gastric fundus ablation “may represent, and frankly should represent, a treatment option for the greater than 100 million US adults with obesity,” he added.

Not every patient wants to or can access GLP-1 medications, Dr. McGowan said. Also, “there’s a difference between taking a medication long-term, requiring an injection every week, vs a single intervention in time that carries forward.”

Ablation could also help people transition after they stop GLP-1 medications to help them maintain their weight loss, he said.

Weight loss is the endpoint you care about the most, said Dr. Laine, who co-moderated the press briefing.

Though the weight loss of 7.7% was not a large percentage, it was only 10 patients. We will have to see whether the total body weight loss is different when they do the procedure in more patients or if they can combine different mechanisms, Dr. Laine said.

It remains unclear whether gastric fundus ablation would be a stand-alone procedure or used in combination with another endoscopic weight-management intervention, bariatric surgery, or medication.

The endoscopic sleeve, which is a stomach-reducing procedure, is very effective, but it doesn’t diminish hunger, Dr. McGowan said. Combining it with ablation may be “a best-of-both-worlds scenario.”

Dr. Laine added that another open question is whether the gastric fundal accommodation will be associated with any side effects such as dyspepsia.

Dr. McGowan reported consulting for Boston Scientific and Apollo Endosurgery. Dr. Laine reported no relevant financial relationships.

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

Screenings may not be the way to get needed resources to children and their caregivers, according to new research presented at the annual meeting of the Pediatric Academic Societies (PAS).

Caregivers and parents who were asked if they wanted assistance in several areas of need, including transportation and childcare, were nearly twice as likely to say they wanted such help than those who received a screening on current hardships. Generally, each questionnaire is administered in front of their children in primary care or pediatric hospital settings.

“Families have a lot of concern about being seen a different way by their healthcare team, being seen as unfit, and having child protective services involved in their childcare for issues related to poverty,” said Danielle Cullen, MD, a pediatric emergency medicine specialist at Children’s Hospital of Philadelphia (CHOP) and assistant professor of pediatrics at the University of Pennsylvania in Philadelphia.

Dr. Cullen and her colleagues analyzed data from nearly 4000 caregivers of children up to age 21 at emergency departments or primary care clinics at CHOP between 2021 and 2023.

Caregivers were randomly assigned to one of three arms — screening with a version of WE CARE (Well Child Care, Evaluation, Community Resources, Advocacy, Referral, Education), use of an online menu of options for help in areas like housing, or neither approach.

Caregivers in all three arms received a map of resources and a follow-up text from a resource navigator to assist them as needed.

Nearly 40% of caregivers who presented with the digital menu said they wanted resources compared with 29% of those who were screened (P < .001). Non-native English speakers given the menu were 2.5 times more likely to say yes to resources compared with those who were screened.

“We need to be thoughtful about these mandates to screen for social determinants of health: It’s not that straightforward,” said Esther K. Chung, MD, a pediatrician and professor of pediatrics at the University of Washington Medicine in Seattle, who was not involved in the study. “What we’re getting from this study is that patients want choice, and the menu provides them choice.”

Dr. Cullen said the menu option allows caregivers to make choices based on their priorities and not on whether they meet the screening thresholds for need.

While some health clinics utilize tablet forms for screenings to offer more privacy with questions, asking direct questions about income, food insecurity, and housing stability can be stigmatizing, Dr. Cullen said.

“Screening positive for social risk doesn’t mean that you actually want resources, and on the flip side, the literature shows that about half of the people who screen negative want resources,” she said.

Dr. Cullen and her team also conducted follow-up interviews with caregivers and found many feared that their clinician would assume a medical condition was connected to living conditions. They also had concerns about insurance companies gaining access to the data and using it to deny coverage or raise costs.

Spanish-speaking caregivers cited fears about their immigration status, experiences of discrimination, and language barriers when trying to access resources.

Participants said a few key strategies could make screening less intimidating, such as abstaining from screening during a serious medical visit, asking for consent to record answers in medical records, and communicating in an empathetic manner.

“Some families are a bit surprised when we ask about things like housing and food insecurity, but I think as long as we contextualize it, we can minimize the stigma associated with it,” Dr. Chung said. “That takes quite a bit of nuance and skill.”

The study was funded by the William T. Grant Foundation and the Emergency Medicine Foundation. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

Screenings may not be the way to get needed resources to children and their caregivers, according to new research presented at the annual meeting of the Pediatric Academic Societies (PAS).

Caregivers and parents who were asked if they wanted assistance in several areas of need, including transportation and childcare, were nearly twice as likely to say they wanted such help than those who received a screening on current hardships. Generally, each questionnaire is administered in front of their children in primary care or pediatric hospital settings.

“Families have a lot of concern about being seen a different way by their healthcare team, being seen as unfit, and having child protective services involved in their childcare for issues related to poverty,” said Danielle Cullen, MD, a pediatric emergency medicine specialist at Children’s Hospital of Philadelphia (CHOP) and assistant professor of pediatrics at the University of Pennsylvania in Philadelphia.

Dr. Cullen and her colleagues analyzed data from nearly 4000 caregivers of children up to age 21 at emergency departments or primary care clinics at CHOP between 2021 and 2023.

Caregivers were randomly assigned to one of three arms — screening with a version of WE CARE (Well Child Care, Evaluation, Community Resources, Advocacy, Referral, Education), use of an online menu of options for help in areas like housing, or neither approach.

Caregivers in all three arms received a map of resources and a follow-up text from a resource navigator to assist them as needed.

Nearly 40% of caregivers who presented with the digital menu said they wanted resources compared with 29% of those who were screened (P < .001). Non-native English speakers given the menu were 2.5 times more likely to say yes to resources compared with those who were screened.

“We need to be thoughtful about these mandates to screen for social determinants of health: It’s not that straightforward,” said Esther K. Chung, MD, a pediatrician and professor of pediatrics at the University of Washington Medicine in Seattle, who was not involved in the study. “What we’re getting from this study is that patients want choice, and the menu provides them choice.”

Dr. Cullen said the menu option allows caregivers to make choices based on their priorities and not on whether they meet the screening thresholds for need.

While some health clinics utilize tablet forms for screenings to offer more privacy with questions, asking direct questions about income, food insecurity, and housing stability can be stigmatizing, Dr. Cullen said.

“Screening positive for social risk doesn’t mean that you actually want resources, and on the flip side, the literature shows that about half of the people who screen negative want resources,” she said.

Dr. Cullen and her team also conducted follow-up interviews with caregivers and found many feared that their clinician would assume a medical condition was connected to living conditions. They also had concerns about insurance companies gaining access to the data and using it to deny coverage or raise costs.

Spanish-speaking caregivers cited fears about their immigration status, experiences of discrimination, and language barriers when trying to access resources.

Participants said a few key strategies could make screening less intimidating, such as abstaining from screening during a serious medical visit, asking for consent to record answers in medical records, and communicating in an empathetic manner.

“Some families are a bit surprised when we ask about things like housing and food insecurity, but I think as long as we contextualize it, we can minimize the stigma associated with it,” Dr. Chung said. “That takes quite a bit of nuance and skill.”

The study was funded by the William T. Grant Foundation and the Emergency Medicine Foundation. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

Screenings may not be the way to get needed resources to children and their caregivers, according to new research presented at the annual meeting of the Pediatric Academic Societies (PAS).

Caregivers and parents who were asked if they wanted assistance in several areas of need, including transportation and childcare, were nearly twice as likely to say they wanted such help than those who received a screening on current hardships. Generally, each questionnaire is administered in front of their children in primary care or pediatric hospital settings.

“Families have a lot of concern about being seen a different way by their healthcare team, being seen as unfit, and having child protective services involved in their childcare for issues related to poverty,” said Danielle Cullen, MD, a pediatric emergency medicine specialist at Children’s Hospital of Philadelphia (CHOP) and assistant professor of pediatrics at the University of Pennsylvania in Philadelphia.

Dr. Cullen and her colleagues analyzed data from nearly 4000 caregivers of children up to age 21 at emergency departments or primary care clinics at CHOP between 2021 and 2023.

Caregivers were randomly assigned to one of three arms — screening with a version of WE CARE (Well Child Care, Evaluation, Community Resources, Advocacy, Referral, Education), use of an online menu of options for help in areas like housing, or neither approach.

Caregivers in all three arms received a map of resources and a follow-up text from a resource navigator to assist them as needed.

Nearly 40% of caregivers who presented with the digital menu said they wanted resources compared with 29% of those who were screened (P < .001). Non-native English speakers given the menu were 2.5 times more likely to say yes to resources compared with those who were screened.

“We need to be thoughtful about these mandates to screen for social determinants of health: It’s not that straightforward,” said Esther K. Chung, MD, a pediatrician and professor of pediatrics at the University of Washington Medicine in Seattle, who was not involved in the study. “What we’re getting from this study is that patients want choice, and the menu provides them choice.”

Dr. Cullen said the menu option allows caregivers to make choices based on their priorities and not on whether they meet the screening thresholds for need.

While some health clinics utilize tablet forms for screenings to offer more privacy with questions, asking direct questions about income, food insecurity, and housing stability can be stigmatizing, Dr. Cullen said.

“Screening positive for social risk doesn’t mean that you actually want resources, and on the flip side, the literature shows that about half of the people who screen negative want resources,” she said.

Dr. Cullen and her team also conducted follow-up interviews with caregivers and found many feared that their clinician would assume a medical condition was connected to living conditions. They also had concerns about insurance companies gaining access to the data and using it to deny coverage or raise costs.

Spanish-speaking caregivers cited fears about their immigration status, experiences of discrimination, and language barriers when trying to access resources.

Participants said a few key strategies could make screening less intimidating, such as abstaining from screening during a serious medical visit, asking for consent to record answers in medical records, and communicating in an empathetic manner.

“Some families are a bit surprised when we ask about things like housing and food insecurity, but I think as long as we contextualize it, we can minimize the stigma associated with it,” Dr. Chung said. “That takes quite a bit of nuance and skill.”

The study was funded by the William T. Grant Foundation and the Emergency Medicine Foundation. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to tarlatamab-dlle (Imdelltra) for extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 on the surface of cells, including tumor cells, and CD3 expressed on the surface of T cells. It causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells, according to labeling. 

Approval was based on data from 99 patients in the DeLLphi-301 trial with relapsed/refractory extensive-stage SCLC who had progressed after platinum-based chemotherapy. Patients with symptomatic brain metastases, interstitial lung disease, noninfectious pneumonitis, and active immunodeficiency were excluded. 

The overall response rate was 40%, and median duration of response 9.7 months. The overall response rate was 52% in 27 patients with platinum-resistant SCLC and 31% in 42 with platinum-sensitive disease. 

Continued approval may depend on verification of clinical benefit in a confirmatory trial.

Labeling includes a box warning of serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome. 

The most common adverse events, occurring in 20% or more of patients, were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea. 

The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.

The starting dose is 1 mg given intravenously over 1 hour on the first day of the first cycle followed by 10 mg on day 8 and day 15 of the first cycle, then every 2 weeks until disease progression or unacceptable toxicity.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to tarlatamab-dlle (Imdelltra) for extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 on the surface of cells, including tumor cells, and CD3 expressed on the surface of T cells. It causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells, according to labeling. 

Approval was based on data from 99 patients in the DeLLphi-301 trial with relapsed/refractory extensive-stage SCLC who had progressed after platinum-based chemotherapy. Patients with symptomatic brain metastases, interstitial lung disease, noninfectious pneumonitis, and active immunodeficiency were excluded. 

The overall response rate was 40%, and median duration of response 9.7 months. The overall response rate was 52% in 27 patients with platinum-resistant SCLC and 31% in 42 with platinum-sensitive disease. 

Continued approval may depend on verification of clinical benefit in a confirmatory trial.

Labeling includes a box warning of serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome. 

The most common adverse events, occurring in 20% or more of patients, were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea. 

The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.

The starting dose is 1 mg given intravenously over 1 hour on the first day of the first cycle followed by 10 mg on day 8 and day 15 of the first cycle, then every 2 weeks until disease progression or unacceptable toxicity.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to tarlatamab-dlle (Imdelltra) for extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 on the surface of cells, including tumor cells, and CD3 expressed on the surface of T cells. It causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells, according to labeling. 

Approval was based on data from 99 patients in the DeLLphi-301 trial with relapsed/refractory extensive-stage SCLC who had progressed after platinum-based chemotherapy. Patients with symptomatic brain metastases, interstitial lung disease, noninfectious pneumonitis, and active immunodeficiency were excluded. 

The overall response rate was 40%, and median duration of response 9.7 months. The overall response rate was 52% in 27 patients with platinum-resistant SCLC and 31% in 42 with platinum-sensitive disease. 

Continued approval may depend on verification of clinical benefit in a confirmatory trial.

Labeling includes a box warning of serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome. 

The most common adverse events, occurring in 20% or more of patients, were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea. 

The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.

The starting dose is 1 mg given intravenously over 1 hour on the first day of the first cycle followed by 10 mg on day 8 and day 15 of the first cycle, then every 2 weeks until disease progression or unacceptable toxicity.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com

A version of this article appeared on Medscape.com.

Adding atezolizumab to chemotherapy in patients with anti–programmed death ligand 1 (PD-L1)–positive triple-negative breast cancer (TNBC) who have relapsed within 12 months of their last curative treatment does not improve their survival, results of the IMpassion132 trial show.

Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

“These patients have a dismal prognosis and represent a high unmet need,” she added. 

The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.

Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.

“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”

IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.

Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.

Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.

Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.

The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.

The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.

After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).

A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.

Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”

The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.

There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.

“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”

The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.

Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse. 

This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.” 

The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.

IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.

“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”

The study was sponsored by Hoffmann-La Roche.

Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.

A version of this article appeared on Medscape.com .

Adding atezolizumab to chemotherapy in patients with anti–programmed death ligand 1 (PD-L1)–positive triple-negative breast cancer (TNBC) who have relapsed within 12 months of their last curative treatment does not improve their survival, results of the IMpassion132 trial show.

Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

“These patients have a dismal prognosis and represent a high unmet need,” she added. 

The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.

Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.

“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”

IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.

Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.

Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.

Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.

The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.

The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.

After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).

A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.

Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”

The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.

There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.

“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”

The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.

Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse. 

This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.” 

The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.

IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.

“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”

The study was sponsored by Hoffmann-La Roche.

Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.

A version of this article appeared on Medscape.com .

Adding atezolizumab to chemotherapy in patients with anti–programmed death ligand 1 (PD-L1)–positive triple-negative breast cancer (TNBC) who have relapsed within 12 months of their last curative treatment does not improve their survival, results of the IMpassion132 trial show.

Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

“These patients have a dismal prognosis and represent a high unmet need,” she added. 

The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.

Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.

“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”

IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.

Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.

Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.

Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.

The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.

The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.

After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).

A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.

Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”

The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.

There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.

“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”

The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.

Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse. 

This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.” 

The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.

IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.

“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”

The study was sponsored by Hoffmann-La Roche.

Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.

A version of this article appeared on Medscape.com .

No matter where one looks for the statistics, no matter what words one chooses to describe it, this country has a child and adolescent mental health crisis. Almost 20% of young people in the 3-17 age bracket have a mental, emotional, developmental, or behavioral disorder. COVID-19 has certainly exacerbated the problem, but the downward trend in the mental health of this nation has been going on for decades.

The voices calling for more services to address the problem are getting more numerous and louder. But, what exactly should those services look like and who should be delivering them?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

No matter where one looks for the statistics, no matter what words one chooses to describe it, this country has a child and adolescent mental health crisis. Almost 20% of young people in the 3-17 age bracket have a mental, emotional, developmental, or behavioral disorder. COVID-19 has certainly exacerbated the problem, but the downward trend in the mental health of this nation has been going on for decades.

The voices calling for more services to address the problem are getting more numerous and louder. But, what exactly should those services look like and who should be delivering them?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

No matter where one looks for the statistics, no matter what words one chooses to describe it, this country has a child and adolescent mental health crisis. Almost 20% of young people in the 3-17 age bracket have a mental, emotional, developmental, or behavioral disorder. COVID-19 has certainly exacerbated the problem, but the downward trend in the mental health of this nation has been going on for decades.

The voices calling for more services to address the problem are getting more numerous and louder. But, what exactly should those services look like and who should be delivering them?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.