Heidi Splete

Many of the persistent problems that breast cancer survivors experience after treatment are not part of the conversation with oncologists during treatment, said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.

Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.

In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.

In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.

Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.

Shift to primary care

As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.

A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
 

Delivering the three P’s

The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .

The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.

The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.

The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.

Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.

To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.

For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.

Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.

However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.

During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
 

Engaging a patient’s partner early can be helpful

If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.

“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”

“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.

Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.

Many of the persistent problems that breast cancer survivors experience after treatment are not part of the conversation with oncologists during treatment, said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.

Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.

In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.

In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.

Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.

Shift to primary care

As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.

A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
 

Delivering the three P’s

The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .

The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.

The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.

The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.

Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.

To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.

For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.

Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.

However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.

During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
 

Engaging a patient’s partner early can be helpful

If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.

“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”

“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.

Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.

Many of the persistent problems that breast cancer survivors experience after treatment are not part of the conversation with oncologists during treatment, said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.

Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.

In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.

In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.

Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.

Shift to primary care

As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.

A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
 

Delivering the three P’s

The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .

The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.

The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.

The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.

Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.

To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.

For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.

Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.

However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.

During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
 

Engaging a patient’s partner early can be helpful

If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.

“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”

“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.

Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.

The investigational drug brepocitinib showed superior symptom reduction in adults with moderate to severe active psoriatic arthritis (PsA), compared with placebo, by meeting primary and secondary endpoints of a phase 2b trial at 16 weeks, which persisted out to 1 year, according to data from 218 individuals.

Brepocitinib, a combination tyrosine kinase 2 and Janus kinase 1 inhibitor, is being studied for the treatment of several immunologic diseases including PsA, wrote Philip Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health and the University of Washington, both in Seattle.

Previous studies in patients with PsA support the use of Janus kinase inhibitors and demonstrate the efficacy of tyrosine kinase 2 inhibitors, but more data are needed in patients with active PsA, the researchers noted.

In a study published in Arthritis & Rheumatology, the researchers randomized adults aged 18-75 years with moderate to severe PsA to once-daily oral doses of brepocitinib at 10 mg, 30 mg, or 60 mg, or a placebo for 16 weeks to assess safety, efficacy, and dose response. Placebo-treated patients were advanced to 30 mg or 60 mg of brepocitinib at week 16. Baseline demographics and disease characteristics were similar among the treatment groups. The mean Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for PsA scores were 5.6 and 38.2, respectively, for the overall study population. Approximately two-thirds (64.7%) had a baseline Psoriasis Area and Severity Index (PASI) score greater than 0 and 3% or more of their body surface area affected by psoriasis.

The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 16. Secondary endpoints included rates of patients meeting ACR 50 and ACR 70 response criteria, the proportion of patients achieving 75% and 90% improvement in PASI scores (PASI 70 and 90), as well as the rates of patients meeting Minimal Disease Activity (MDA) criteria at 16 and 52 weeks.

At week 16, ACR 20 response rates were significantly higher in the brepocitinib 30-mg and 60-mg groups, compared with the placebo group (66.7% and 74.6%, respectively, vs. 43.3%), but not for those who received brepocitinib 10 mg (64.5%).

Response rates for ACR 50, ACR 70, PASI 75, PASI 90, and MDA were similarly higher in the 30-mg and 60-mg brepocitinib groups, compared with placebo, and these responses persisted at week 52. Notably, significant differences in PASI 75 and PASI 90 were observed in patients taking 30 mg and 60 mg brepocitinib, compared with placebo, as early as weeks 4 and 8, respectively, the researchers said.

In addition, disease activity based on PASDAS improved significantly more from baseline to week 16 in all brepocitinib groups, compared with placebo.

The overall safety data were consistent with previous brepocitinib studies, and most of the adverse events were mild or moderate, the researchers said. A total of 12 participants (5.5%) experienced a total of 15 serious adverse events, including 6 infections with brepocitinib 30 mg or 60 mg. No major adverse cardiovascular events or deaths occurred during the study period.

The findings were limited by several factors, including the use of clinics in a limited geographic area (11 countries in Europe), small sample size, and mainly White population, the researchers noted. Other limitations included the large placebo effect and relatively short placebo-controlled period.

The study was supported by Pfizer. Dr. Mease disclosed relationships with Pfizer and other companies including AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Sun, and UCB. Many coauthors were employees of Pfizer, and others reported financial relationships with Pfizer and other pharmaceutical companies.

The investigational drug brepocitinib showed superior symptom reduction in adults with moderate to severe active psoriatic arthritis (PsA), compared with placebo, by meeting primary and secondary endpoints of a phase 2b trial at 16 weeks, which persisted out to 1 year, according to data from 218 individuals.

Brepocitinib, a combination tyrosine kinase 2 and Janus kinase 1 inhibitor, is being studied for the treatment of several immunologic diseases including PsA, wrote Philip Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health and the University of Washington, both in Seattle.

Previous studies in patients with PsA support the use of Janus kinase inhibitors and demonstrate the efficacy of tyrosine kinase 2 inhibitors, but more data are needed in patients with active PsA, the researchers noted.

In a study published in Arthritis & Rheumatology, the researchers randomized adults aged 18-75 years with moderate to severe PsA to once-daily oral doses of brepocitinib at 10 mg, 30 mg, or 60 mg, or a placebo for 16 weeks to assess safety, efficacy, and dose response. Placebo-treated patients were advanced to 30 mg or 60 mg of brepocitinib at week 16. Baseline demographics and disease characteristics were similar among the treatment groups. The mean Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for PsA scores were 5.6 and 38.2, respectively, for the overall study population. Approximately two-thirds (64.7%) had a baseline Psoriasis Area and Severity Index (PASI) score greater than 0 and 3% or more of their body surface area affected by psoriasis.

The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 16. Secondary endpoints included rates of patients meeting ACR 50 and ACR 70 response criteria, the proportion of patients achieving 75% and 90% improvement in PASI scores (PASI 70 and 90), as well as the rates of patients meeting Minimal Disease Activity (MDA) criteria at 16 and 52 weeks.

At week 16, ACR 20 response rates were significantly higher in the brepocitinib 30-mg and 60-mg groups, compared with the placebo group (66.7% and 74.6%, respectively, vs. 43.3%), but not for those who received brepocitinib 10 mg (64.5%).

Response rates for ACR 50, ACR 70, PASI 75, PASI 90, and MDA were similarly higher in the 30-mg and 60-mg brepocitinib groups, compared with placebo, and these responses persisted at week 52. Notably, significant differences in PASI 75 and PASI 90 were observed in patients taking 30 mg and 60 mg brepocitinib, compared with placebo, as early as weeks 4 and 8, respectively, the researchers said.

In addition, disease activity based on PASDAS improved significantly more from baseline to week 16 in all brepocitinib groups, compared with placebo.

The overall safety data were consistent with previous brepocitinib studies, and most of the adverse events were mild or moderate, the researchers said. A total of 12 participants (5.5%) experienced a total of 15 serious adverse events, including 6 infections with brepocitinib 30 mg or 60 mg. No major adverse cardiovascular events or deaths occurred during the study period.

The findings were limited by several factors, including the use of clinics in a limited geographic area (11 countries in Europe), small sample size, and mainly White population, the researchers noted. Other limitations included the large placebo effect and relatively short placebo-controlled period.

The study was supported by Pfizer. Dr. Mease disclosed relationships with Pfizer and other companies including AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Sun, and UCB. Many coauthors were employees of Pfizer, and others reported financial relationships with Pfizer and other pharmaceutical companies.

The investigational drug brepocitinib showed superior symptom reduction in adults with moderate to severe active psoriatic arthritis (PsA), compared with placebo, by meeting primary and secondary endpoints of a phase 2b trial at 16 weeks, which persisted out to 1 year, according to data from 218 individuals.

Brepocitinib, a combination tyrosine kinase 2 and Janus kinase 1 inhibitor, is being studied for the treatment of several immunologic diseases including PsA, wrote Philip Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health and the University of Washington, both in Seattle.

Previous studies in patients with PsA support the use of Janus kinase inhibitors and demonstrate the efficacy of tyrosine kinase 2 inhibitors, but more data are needed in patients with active PsA, the researchers noted.

In a study published in Arthritis & Rheumatology, the researchers randomized adults aged 18-75 years with moderate to severe PsA to once-daily oral doses of brepocitinib at 10 mg, 30 mg, or 60 mg, or a placebo for 16 weeks to assess safety, efficacy, and dose response. Placebo-treated patients were advanced to 30 mg or 60 mg of brepocitinib at week 16. Baseline demographics and disease characteristics were similar among the treatment groups. The mean Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for PsA scores were 5.6 and 38.2, respectively, for the overall study population. Approximately two-thirds (64.7%) had a baseline Psoriasis Area and Severity Index (PASI) score greater than 0 and 3% or more of their body surface area affected by psoriasis.

The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 16. Secondary endpoints included rates of patients meeting ACR 50 and ACR 70 response criteria, the proportion of patients achieving 75% and 90% improvement in PASI scores (PASI 70 and 90), as well as the rates of patients meeting Minimal Disease Activity (MDA) criteria at 16 and 52 weeks.

At week 16, ACR 20 response rates were significantly higher in the brepocitinib 30-mg and 60-mg groups, compared with the placebo group (66.7% and 74.6%, respectively, vs. 43.3%), but not for those who received brepocitinib 10 mg (64.5%).

Response rates for ACR 50, ACR 70, PASI 75, PASI 90, and MDA were similarly higher in the 30-mg and 60-mg brepocitinib groups, compared with placebo, and these responses persisted at week 52. Notably, significant differences in PASI 75 and PASI 90 were observed in patients taking 30 mg and 60 mg brepocitinib, compared with placebo, as early as weeks 4 and 8, respectively, the researchers said.

In addition, disease activity based on PASDAS improved significantly more from baseline to week 16 in all brepocitinib groups, compared with placebo.

The overall safety data were consistent with previous brepocitinib studies, and most of the adverse events were mild or moderate, the researchers said. A total of 12 participants (5.5%) experienced a total of 15 serious adverse events, including 6 infections with brepocitinib 30 mg or 60 mg. No major adverse cardiovascular events or deaths occurred during the study period.

The findings were limited by several factors, including the use of clinics in a limited geographic area (11 countries in Europe), small sample size, and mainly White population, the researchers noted. Other limitations included the large placebo effect and relatively short placebo-controlled period.

The study was supported by Pfizer. Dr. Mease disclosed relationships with Pfizer and other companies including AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Sun, and UCB. Many coauthors were employees of Pfizer, and others reported financial relationships with Pfizer and other pharmaceutical companies.

Adding neoadjuvant atezolizumab to chemotherapy was associated with a significantly improved response in patients with early-stage triple-negative breast cancer, based on final data from a randomized trial.

The IMpassion031 trial showed significant improvement in pathological complete response (pCR) with the addition of atezolizumab to chemotherapy, as well as an acceptable safety profile, said Carlos H. Barrios, MD, of the Latin American Cooperative Oncology Group, Oncoclinicas, in Porto Allegre, Brazil, at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. Those findings were published in the Lancet in 2020.

Heidi Splete/MDedge News

Dr. Barrios reported data from a final analysis of the IMpassion031 trial, with data on event-free survival (EFS), disease-free survival (DFS) and overall survival (OS) in the intent-to-treat (ITT) and PD-L1–positive populations.

In the study, patients with early triple-negative breast cancer (eTNBC) and a primary tumor greater than 2 cm were randomized to 840 mg of atezolizumab once every 2 weeks plus a neoadjuvant chemotherapy regimen of nab-paclitaxel 125 mg/m² once weekly for 12 weeks, followed by doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m² once every 2 weeks for 8 weeks. A total of 333 patients were randomized (165 atezolizumab and 168 placebo). Patients were stratified by stage II versus stage III, and by status of PD-L1, a protein that can predict treatment response (PD-L1 less than 1% vs. 1% or higher).

The primary endpoints (previously reported) were pathological complete response (pCR) in the ITT and PD-L1 populations. After a median follow-up of 39 months, the pCR was 58% in patients treated with atezolizumab versus 41% in those treated with neoadjuvant chemotherapy alone (P = .0044) in the ITT population, Dr. Barrios said. The added benefit from atezolizumab occurred regardless of the status of PD-L1.

Dr. Barrios reported the secondary outcomes of EFS, DFS, and OS in the intent-to-treat and PD-L1–positive populations. “This is a descriptive analysis, with no statistical comparison,” he emphasized.

The 2-year data on EFS, DFS, and OS consistently favored atezolizumab across key clinical subgroups, Dr. Barrios said. In the ITT population, 2-year EFS, DFS, and OS was 85%, 87%, and 95%, respectively, in the atezolizumab group and 80%, 83%, and 90%, respectively, in the placebo group. The results were similar, irrespective of PD-L1 status.

In the PD-L1–positive population, 2-year EFS, DFS, and OS was 89%, 91%, and 95%, respectively, in atezolizumab patients and 80%, 87%, and 91% in placebo patients.

Among patients without pCR at the time of surgery, 14 of 70 patients (20%) in the atezolizumab group and 33 of 99 patients (33%) in the placebo group received additional adjuvant systemic therapy. The most common adjunctive therapy was capecitabine.

As for safety, no new safety signals or treatment-related deaths were observed in the study. Overall, 70% of atezolizumab patients and 62% of placebo patients experienced grade 3 or 4 adverse events (AEs); 59% and 54% of which were treatment related. A total of 1% of patients in each group experienced grade 5 AEs. A total of 25% of atezolizumab patients and 20% of placebo patients experienced AEs leading to treatment discontinuation.

In a further exploratory analysis, pCR was highly predictive of long-term outcomes. Exploratory analysis of circulating tumor DNA (ctDNA) showed clearance in 89% of atezolizumab patients and 86% of placebo patients by the time of surgery.

Looking at the relationship between ctDNA, DFS, and OS, positive ctDNA was associated with a worse prognosis following surgery. As demonstrated in previous studies, pCR patients with negative ctDNA had the best DFS and OS. “In non-pCR patients with positive ctDNA, a numerical trend suggests improved overall survival with atezolizumab,” although the caveat is the very small numbers, Dr. Barrios said.

More research is needed, but in the final analysis, the significant pCR benefit seen with the addition of atezolizumab to chemotherapy for eTNBC translated into numerically improved EFS, DFS and OS, said Dr. Barrios. Additionally, “we should further analyze ctDNA to help select patients for further therapy.”

In a question-and-answer session, Dr. Barrios was asked how the results compared with other studies.

“We should not overinterpret the results,” he said. However, “what the IMpassion031 study shows is consistency; the results are aligned with previous studies addressing the same question of introducing immunotherapy,” in the patient population. Although the numbers in the IMpassion031 study did not reach statistical significance, it is important to recognize that they reflect previous research.

“In my opinion, looking at the whole field, immunotherapy is something we need to consider as part of the treatment of these patients,” said Dr. Barrios. However, more research is needed to better identify which patients do and do not need chemotherapy.
 

Phase 2 data show increased response with added atezolizumab for PD-L1–negative patients

In a second study known as ABSCG-52/ATHENE, researchers evaluated neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin for the treatment of patients with early HER2-positive breast cancer.

Heidi Splete/MDedge News

For most of these patients, the current standard of care is neoadjuvant dual HER2 blockade with trastuzumab (T) and pertuzumab (P) plus poly-chemotherapy, said Gabriel Rinnerthaler, MD, of the Salzburg (Austria) Cancer Research Institute, said in his presentation at the meeting. However, de-escalation of chemotherapy has been a major focus of research in recent years, and more research is needed on a combination of anthracyclines, such as epirubicin and idarubicin, and immune-checkpoint modulators.

In the phase 2 study, the researchers randomized patients with previously untreated, histologically confirmed HER2-positive early breast cancer (defined as a clinical prognostic stage cT1c–4a-d, N0-3, M0) in a 1:1 ratio to two 3-weekly cycles of a chemotherapy-free induction phase (part 1) with TP plus 1,200 mg atezolizumab (TP-A) or TP alone.

“We hypothesized that the additive effect of immune checkpoint inhibitors plus anti-HER2 therapy and chemotherapy would not be linear,” he said.

At the end of this period, all patients underwent four cycles of TP-A in combination with epirubicin (part 2). The primary endpoint was pCR (defined as absence of invasive cancer in the breast and axillary nodes, or ypT0/Tis ypN0) in the overall study population, and a pCR of 40% was considered a positive result.

A total of 29 patients were randomized to TP-A and 29 to TP alone in nine treatment centers in Austria. The study population ranged from 33 to 82 years, with a median age of 57 years. Most patients (72.4%) had hormone receptor (HR)–positive tumors; a total of 45 patients had stage IIA cancer, and 13 had stage IIB.

The primary endpoint of pCR occurred in 35 patients overall (60.3%). In a univariate analysis, the response rates were lower in HR-positive patients, in premenopausal patients, and in histologies other than NST (invasive carcinoma of no special type), Dr. Rinnerthaler said, but none of the differences were statistically significant, likely because of the small numbers in each group.

In an exploratory analysis of the ITT population with available PD-L1 data, the pCR was 69.2% for PD-L1–negative patients and 55.2% for PD-L1–positive patients.

“We observed the highest pCR rates in PD-L1–negative patients treated in the TP-A group and the lowest in PD-L1–positive patients treated with TP alone,” Dr. Rinnerthaler said.

No new safety concerns were observed during the study, Dr. Rinnerthaler noted. AEs of grade 3 or higher occurred in 17 patients (29.3%), including 9 in the TP-A group and 8 in the TP group. The most common AEs in both groups were nausea, diarrhea, and fatigue. No AEs of special interest of grade 3 or higher (defined as immune-related AEs, cardiac disorders, or infusion-related reactions) were observed.

The study findings were limited by the small sample size, but the resulting pCR rate of 60.3% was higher than the predefined threshold of 40% and supports additional research, said Dr. Rinnerthaler.

“For HER2-positive early breast cancer, a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab, and epirubicin is highly effective and safe and merits further investigation,” he concluded.

During a question-and-answer session, Dr. Rinnerthaler was asked why pCR increased in PD-L1 negative patients.

Previous data have shown that PD-L1 is up-regulated in certain tumors, and may serve as a surrogate for sensitivity, he said. In previous studies the additional effect of atezolizumab was seen in a PD-L1–negative group.

Dr. Rinnerthaler said he hopes to clarify this question when his research team reviews biopsy data from baseline and after the induction phase.
 

Defining response is key to de-escalation

In the IMpassion031 trial, “what we saw is a tendency to better outcomes for those patients who received atezolizumab,” said Matteo Lambertini, MD, of the University of Genova (Italy), who served as discussant for the two studies. The IMpassion031 study raises the question of where we are in the use of immuno-oncology for eTNBC. The study is now one of five neoadjuvant trials in this population.

Heidi Splete/MDedge News

Dr. Lambertini cited the KEYNOTE-522 study, which showed significant results in EFS. However, sample sizes and statistical design were different between these studies. “I think we need large studies of data in the adjuvant and postneoadjuvant setting for patients with triple-negative breast cancer.”

Postneoadjuvant considerations from the IMpassion031 trial showed good outcomes with no additional benefit of an immune checkpoint inhibitors.

For those patients with a pCR, it is definitely time to de-escalate treatment,” he said. In patients without pCR, escalation is needed, but an improved definition of pCR is also needed.

With regard to the ATHENE study, “it may be considered a positive study because the threshold of 40% was reached,” he said. The question is what is the optimum chemotherapy backbone. There appears to be no added benefit to adding an immune checkpoint inhibitor.

There are needs for defining the role of immunotherapy in HER2-positive breast cancer and more biomarker research to inform patient selection and study design, he said.

Finally, “I am not sure that the addition of an immune checkpoint inhibitor can be considered a de-escalation,” he noted.

IMpassion031 was supported by F. Hoffmann–La Roche. Dr. Barrio disclosed financial relationships with numerous companies. ABSCG-52/ATHENE was supported by the Austrian Breast and Colorectal Cancer Study Group and Roche Austria. Dr. Rinnerthaler disclosed relationships with multiple companies including Amgen, Daiichi Sankyo, Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Seagen, and Pierre Fabre. Dr. Lambertini disclosed relationships with multiple companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, MSD, Seagen, Gilead, Takeda, Sandoz, Ipsen, Libbs, Knight, and Daiichi Sankyo.

Adding neoadjuvant atezolizumab to chemotherapy was associated with a significantly improved response in patients with early-stage triple-negative breast cancer, based on final data from a randomized trial.

The IMpassion031 trial showed significant improvement in pathological complete response (pCR) with the addition of atezolizumab to chemotherapy, as well as an acceptable safety profile, said Carlos H. Barrios, MD, of the Latin American Cooperative Oncology Group, Oncoclinicas, in Porto Allegre, Brazil, at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. Those findings were published in the Lancet in 2020.

Heidi Splete/MDedge News

Dr. Barrios reported data from a final analysis of the IMpassion031 trial, with data on event-free survival (EFS), disease-free survival (DFS) and overall survival (OS) in the intent-to-treat (ITT) and PD-L1–positive populations.

In the study, patients with early triple-negative breast cancer (eTNBC) and a primary tumor greater than 2 cm were randomized to 840 mg of atezolizumab once every 2 weeks plus a neoadjuvant chemotherapy regimen of nab-paclitaxel 125 mg/m² once weekly for 12 weeks, followed by doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m² once every 2 weeks for 8 weeks. A total of 333 patients were randomized (165 atezolizumab and 168 placebo). Patients were stratified by stage II versus stage III, and by status of PD-L1, a protein that can predict treatment response (PD-L1 less than 1% vs. 1% or higher).

The primary endpoints (previously reported) were pathological complete response (pCR) in the ITT and PD-L1 populations. After a median follow-up of 39 months, the pCR was 58% in patients treated with atezolizumab versus 41% in those treated with neoadjuvant chemotherapy alone (P = .0044) in the ITT population, Dr. Barrios said. The added benefit from atezolizumab occurred regardless of the status of PD-L1.

Dr. Barrios reported the secondary outcomes of EFS, DFS, and OS in the intent-to-treat and PD-L1–positive populations. “This is a descriptive analysis, with no statistical comparison,” he emphasized.

The 2-year data on EFS, DFS, and OS consistently favored atezolizumab across key clinical subgroups, Dr. Barrios said. In the ITT population, 2-year EFS, DFS, and OS was 85%, 87%, and 95%, respectively, in the atezolizumab group and 80%, 83%, and 90%, respectively, in the placebo group. The results were similar, irrespective of PD-L1 status.

In the PD-L1–positive population, 2-year EFS, DFS, and OS was 89%, 91%, and 95%, respectively, in atezolizumab patients and 80%, 87%, and 91% in placebo patients.

Among patients without pCR at the time of surgery, 14 of 70 patients (20%) in the atezolizumab group and 33 of 99 patients (33%) in the placebo group received additional adjuvant systemic therapy. The most common adjunctive therapy was capecitabine.

As for safety, no new safety signals or treatment-related deaths were observed in the study. Overall, 70% of atezolizumab patients and 62% of placebo patients experienced grade 3 or 4 adverse events (AEs); 59% and 54% of which were treatment related. A total of 1% of patients in each group experienced grade 5 AEs. A total of 25% of atezolizumab patients and 20% of placebo patients experienced AEs leading to treatment discontinuation.

In a further exploratory analysis, pCR was highly predictive of long-term outcomes. Exploratory analysis of circulating tumor DNA (ctDNA) showed clearance in 89% of atezolizumab patients and 86% of placebo patients by the time of surgery.

Looking at the relationship between ctDNA, DFS, and OS, positive ctDNA was associated with a worse prognosis following surgery. As demonstrated in previous studies, pCR patients with negative ctDNA had the best DFS and OS. “In non-pCR patients with positive ctDNA, a numerical trend suggests improved overall survival with atezolizumab,” although the caveat is the very small numbers, Dr. Barrios said.

More research is needed, but in the final analysis, the significant pCR benefit seen with the addition of atezolizumab to chemotherapy for eTNBC translated into numerically improved EFS, DFS and OS, said Dr. Barrios. Additionally, “we should further analyze ctDNA to help select patients for further therapy.”

In a question-and-answer session, Dr. Barrios was asked how the results compared with other studies.

“We should not overinterpret the results,” he said. However, “what the IMpassion031 study shows is consistency; the results are aligned with previous studies addressing the same question of introducing immunotherapy,” in the patient population. Although the numbers in the IMpassion031 study did not reach statistical significance, it is important to recognize that they reflect previous research.

“In my opinion, looking at the whole field, immunotherapy is something we need to consider as part of the treatment of these patients,” said Dr. Barrios. However, more research is needed to better identify which patients do and do not need chemotherapy.
 

Phase 2 data show increased response with added atezolizumab for PD-L1–negative patients

In a second study known as ABSCG-52/ATHENE, researchers evaluated neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin for the treatment of patients with early HER2-positive breast cancer.

Heidi Splete/MDedge News

For most of these patients, the current standard of care is neoadjuvant dual HER2 blockade with trastuzumab (T) and pertuzumab (P) plus poly-chemotherapy, said Gabriel Rinnerthaler, MD, of the Salzburg (Austria) Cancer Research Institute, said in his presentation at the meeting. However, de-escalation of chemotherapy has been a major focus of research in recent years, and more research is needed on a combination of anthracyclines, such as epirubicin and idarubicin, and immune-checkpoint modulators.

In the phase 2 study, the researchers randomized patients with previously untreated, histologically confirmed HER2-positive early breast cancer (defined as a clinical prognostic stage cT1c–4a-d, N0-3, M0) in a 1:1 ratio to two 3-weekly cycles of a chemotherapy-free induction phase (part 1) with TP plus 1,200 mg atezolizumab (TP-A) or TP alone.

“We hypothesized that the additive effect of immune checkpoint inhibitors plus anti-HER2 therapy and chemotherapy would not be linear,” he said.

At the end of this period, all patients underwent four cycles of TP-A in combination with epirubicin (part 2). The primary endpoint was pCR (defined as absence of invasive cancer in the breast and axillary nodes, or ypT0/Tis ypN0) in the overall study population, and a pCR of 40% was considered a positive result.

A total of 29 patients were randomized to TP-A and 29 to TP alone in nine treatment centers in Austria. The study population ranged from 33 to 82 years, with a median age of 57 years. Most patients (72.4%) had hormone receptor (HR)–positive tumors; a total of 45 patients had stage IIA cancer, and 13 had stage IIB.

The primary endpoint of pCR occurred in 35 patients overall (60.3%). In a univariate analysis, the response rates were lower in HR-positive patients, in premenopausal patients, and in histologies other than NST (invasive carcinoma of no special type), Dr. Rinnerthaler said, but none of the differences were statistically significant, likely because of the small numbers in each group.

In an exploratory analysis of the ITT population with available PD-L1 data, the pCR was 69.2% for PD-L1–negative patients and 55.2% for PD-L1–positive patients.

“We observed the highest pCR rates in PD-L1–negative patients treated in the TP-A group and the lowest in PD-L1–positive patients treated with TP alone,” Dr. Rinnerthaler said.

No new safety concerns were observed during the study, Dr. Rinnerthaler noted. AEs of grade 3 or higher occurred in 17 patients (29.3%), including 9 in the TP-A group and 8 in the TP group. The most common AEs in both groups were nausea, diarrhea, and fatigue. No AEs of special interest of grade 3 or higher (defined as immune-related AEs, cardiac disorders, or infusion-related reactions) were observed.

The study findings were limited by the small sample size, but the resulting pCR rate of 60.3% was higher than the predefined threshold of 40% and supports additional research, said Dr. Rinnerthaler.

“For HER2-positive early breast cancer, a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab, and epirubicin is highly effective and safe and merits further investigation,” he concluded.

During a question-and-answer session, Dr. Rinnerthaler was asked why pCR increased in PD-L1 negative patients.

Previous data have shown that PD-L1 is up-regulated in certain tumors, and may serve as a surrogate for sensitivity, he said. In previous studies the additional effect of atezolizumab was seen in a PD-L1–negative group.

Dr. Rinnerthaler said he hopes to clarify this question when his research team reviews biopsy data from baseline and after the induction phase.
 

Defining response is key to de-escalation

In the IMpassion031 trial, “what we saw is a tendency to better outcomes for those patients who received atezolizumab,” said Matteo Lambertini, MD, of the University of Genova (Italy), who served as discussant for the two studies. The IMpassion031 study raises the question of where we are in the use of immuno-oncology for eTNBC. The study is now one of five neoadjuvant trials in this population.

Heidi Splete/MDedge News

Dr. Lambertini cited the KEYNOTE-522 study, which showed significant results in EFS. However, sample sizes and statistical design were different between these studies. “I think we need large studies of data in the adjuvant and postneoadjuvant setting for patients with triple-negative breast cancer.”

Postneoadjuvant considerations from the IMpassion031 trial showed good outcomes with no additional benefit of an immune checkpoint inhibitors.

For those patients with a pCR, it is definitely time to de-escalate treatment,” he said. In patients without pCR, escalation is needed, but an improved definition of pCR is also needed.

With regard to the ATHENE study, “it may be considered a positive study because the threshold of 40% was reached,” he said. The question is what is the optimum chemotherapy backbone. There appears to be no added benefit to adding an immune checkpoint inhibitor.

There are needs for defining the role of immunotherapy in HER2-positive breast cancer and more biomarker research to inform patient selection and study design, he said.

Finally, “I am not sure that the addition of an immune checkpoint inhibitor can be considered a de-escalation,” he noted.

IMpassion031 was supported by F. Hoffmann–La Roche. Dr. Barrio disclosed financial relationships with numerous companies. ABSCG-52/ATHENE was supported by the Austrian Breast and Colorectal Cancer Study Group and Roche Austria. Dr. Rinnerthaler disclosed relationships with multiple companies including Amgen, Daiichi Sankyo, Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Seagen, and Pierre Fabre. Dr. Lambertini disclosed relationships with multiple companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, MSD, Seagen, Gilead, Takeda, Sandoz, Ipsen, Libbs, Knight, and Daiichi Sankyo.

Adding neoadjuvant atezolizumab to chemotherapy was associated with a significantly improved response in patients with early-stage triple-negative breast cancer, based on final data from a randomized trial.

The IMpassion031 trial showed significant improvement in pathological complete response (pCR) with the addition of atezolizumab to chemotherapy, as well as an acceptable safety profile, said Carlos H. Barrios, MD, of the Latin American Cooperative Oncology Group, Oncoclinicas, in Porto Allegre, Brazil, at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. Those findings were published in the Lancet in 2020.

Heidi Splete/MDedge News

Dr. Barrios reported data from a final analysis of the IMpassion031 trial, with data on event-free survival (EFS), disease-free survival (DFS) and overall survival (OS) in the intent-to-treat (ITT) and PD-L1–positive populations.

In the study, patients with early triple-negative breast cancer (eTNBC) and a primary tumor greater than 2 cm were randomized to 840 mg of atezolizumab once every 2 weeks plus a neoadjuvant chemotherapy regimen of nab-paclitaxel 125 mg/m² once weekly for 12 weeks, followed by doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m² once every 2 weeks for 8 weeks. A total of 333 patients were randomized (165 atezolizumab and 168 placebo). Patients were stratified by stage II versus stage III, and by status of PD-L1, a protein that can predict treatment response (PD-L1 less than 1% vs. 1% or higher).

The primary endpoints (previously reported) were pathological complete response (pCR) in the ITT and PD-L1 populations. After a median follow-up of 39 months, the pCR was 58% in patients treated with atezolizumab versus 41% in those treated with neoadjuvant chemotherapy alone (P = .0044) in the ITT population, Dr. Barrios said. The added benefit from atezolizumab occurred regardless of the status of PD-L1.

Dr. Barrios reported the secondary outcomes of EFS, DFS, and OS in the intent-to-treat and PD-L1–positive populations. “This is a descriptive analysis, with no statistical comparison,” he emphasized.

The 2-year data on EFS, DFS, and OS consistently favored atezolizumab across key clinical subgroups, Dr. Barrios said. In the ITT population, 2-year EFS, DFS, and OS was 85%, 87%, and 95%, respectively, in the atezolizumab group and 80%, 83%, and 90%, respectively, in the placebo group. The results were similar, irrespective of PD-L1 status.

In the PD-L1–positive population, 2-year EFS, DFS, and OS was 89%, 91%, and 95%, respectively, in atezolizumab patients and 80%, 87%, and 91% in placebo patients.

Among patients without pCR at the time of surgery, 14 of 70 patients (20%) in the atezolizumab group and 33 of 99 patients (33%) in the placebo group received additional adjuvant systemic therapy. The most common adjunctive therapy was capecitabine.

As for safety, no new safety signals or treatment-related deaths were observed in the study. Overall, 70% of atezolizumab patients and 62% of placebo patients experienced grade 3 or 4 adverse events (AEs); 59% and 54% of which were treatment related. A total of 1% of patients in each group experienced grade 5 AEs. A total of 25% of atezolizumab patients and 20% of placebo patients experienced AEs leading to treatment discontinuation.

In a further exploratory analysis, pCR was highly predictive of long-term outcomes. Exploratory analysis of circulating tumor DNA (ctDNA) showed clearance in 89% of atezolizumab patients and 86% of placebo patients by the time of surgery.

Looking at the relationship between ctDNA, DFS, and OS, positive ctDNA was associated with a worse prognosis following surgery. As demonstrated in previous studies, pCR patients with negative ctDNA had the best DFS and OS. “In non-pCR patients with positive ctDNA, a numerical trend suggests improved overall survival with atezolizumab,” although the caveat is the very small numbers, Dr. Barrios said.

More research is needed, but in the final analysis, the significant pCR benefit seen with the addition of atezolizumab to chemotherapy for eTNBC translated into numerically improved EFS, DFS and OS, said Dr. Barrios. Additionally, “we should further analyze ctDNA to help select patients for further therapy.”

In a question-and-answer session, Dr. Barrios was asked how the results compared with other studies.

“We should not overinterpret the results,” he said. However, “what the IMpassion031 study shows is consistency; the results are aligned with previous studies addressing the same question of introducing immunotherapy,” in the patient population. Although the numbers in the IMpassion031 study did not reach statistical significance, it is important to recognize that they reflect previous research.

“In my opinion, looking at the whole field, immunotherapy is something we need to consider as part of the treatment of these patients,” said Dr. Barrios. However, more research is needed to better identify which patients do and do not need chemotherapy.
 

Phase 2 data show increased response with added atezolizumab for PD-L1–negative patients

In a second study known as ABSCG-52/ATHENE, researchers evaluated neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin for the treatment of patients with early HER2-positive breast cancer.

Heidi Splete/MDedge News

For most of these patients, the current standard of care is neoadjuvant dual HER2 blockade with trastuzumab (T) and pertuzumab (P) plus poly-chemotherapy, said Gabriel Rinnerthaler, MD, of the Salzburg (Austria) Cancer Research Institute, said in his presentation at the meeting. However, de-escalation of chemotherapy has been a major focus of research in recent years, and more research is needed on a combination of anthracyclines, such as epirubicin and idarubicin, and immune-checkpoint modulators.

In the phase 2 study, the researchers randomized patients with previously untreated, histologically confirmed HER2-positive early breast cancer (defined as a clinical prognostic stage cT1c–4a-d, N0-3, M0) in a 1:1 ratio to two 3-weekly cycles of a chemotherapy-free induction phase (part 1) with TP plus 1,200 mg atezolizumab (TP-A) or TP alone.

“We hypothesized that the additive effect of immune checkpoint inhibitors plus anti-HER2 therapy and chemotherapy would not be linear,” he said.

At the end of this period, all patients underwent four cycles of TP-A in combination with epirubicin (part 2). The primary endpoint was pCR (defined as absence of invasive cancer in the breast and axillary nodes, or ypT0/Tis ypN0) in the overall study population, and a pCR of 40% was considered a positive result.

A total of 29 patients were randomized to TP-A and 29 to TP alone in nine treatment centers in Austria. The study population ranged from 33 to 82 years, with a median age of 57 years. Most patients (72.4%) had hormone receptor (HR)–positive tumors; a total of 45 patients had stage IIA cancer, and 13 had stage IIB.

The primary endpoint of pCR occurred in 35 patients overall (60.3%). In a univariate analysis, the response rates were lower in HR-positive patients, in premenopausal patients, and in histologies other than NST (invasive carcinoma of no special type), Dr. Rinnerthaler said, but none of the differences were statistically significant, likely because of the small numbers in each group.

In an exploratory analysis of the ITT population with available PD-L1 data, the pCR was 69.2% for PD-L1–negative patients and 55.2% for PD-L1–positive patients.

“We observed the highest pCR rates in PD-L1–negative patients treated in the TP-A group and the lowest in PD-L1–positive patients treated with TP alone,” Dr. Rinnerthaler said.

No new safety concerns were observed during the study, Dr. Rinnerthaler noted. AEs of grade 3 or higher occurred in 17 patients (29.3%), including 9 in the TP-A group and 8 in the TP group. The most common AEs in both groups were nausea, diarrhea, and fatigue. No AEs of special interest of grade 3 or higher (defined as immune-related AEs, cardiac disorders, or infusion-related reactions) were observed.

The study findings were limited by the small sample size, but the resulting pCR rate of 60.3% was higher than the predefined threshold of 40% and supports additional research, said Dr. Rinnerthaler.

“For HER2-positive early breast cancer, a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab, and epirubicin is highly effective and safe and merits further investigation,” he concluded.

During a question-and-answer session, Dr. Rinnerthaler was asked why pCR increased in PD-L1 negative patients.

Previous data have shown that PD-L1 is up-regulated in certain tumors, and may serve as a surrogate for sensitivity, he said. In previous studies the additional effect of atezolizumab was seen in a PD-L1–negative group.

Dr. Rinnerthaler said he hopes to clarify this question when his research team reviews biopsy data from baseline and after the induction phase.
 

Defining response is key to de-escalation

In the IMpassion031 trial, “what we saw is a tendency to better outcomes for those patients who received atezolizumab,” said Matteo Lambertini, MD, of the University of Genova (Italy), who served as discussant for the two studies. The IMpassion031 study raises the question of where we are in the use of immuno-oncology for eTNBC. The study is now one of five neoadjuvant trials in this population.

Heidi Splete/MDedge News

Dr. Lambertini cited the KEYNOTE-522 study, which showed significant results in EFS. However, sample sizes and statistical design were different between these studies. “I think we need large studies of data in the adjuvant and postneoadjuvant setting for patients with triple-negative breast cancer.”

Postneoadjuvant considerations from the IMpassion031 trial showed good outcomes with no additional benefit of an immune checkpoint inhibitors.

For those patients with a pCR, it is definitely time to de-escalate treatment,” he said. In patients without pCR, escalation is needed, but an improved definition of pCR is also needed.

With regard to the ATHENE study, “it may be considered a positive study because the threshold of 40% was reached,” he said. The question is what is the optimum chemotherapy backbone. There appears to be no added benefit to adding an immune checkpoint inhibitor.

There are needs for defining the role of immunotherapy in HER2-positive breast cancer and more biomarker research to inform patient selection and study design, he said.

Finally, “I am not sure that the addition of an immune checkpoint inhibitor can be considered a de-escalation,” he noted.

IMpassion031 was supported by F. Hoffmann–La Roche. Dr. Barrio disclosed financial relationships with numerous companies. ABSCG-52/ATHENE was supported by the Austrian Breast and Colorectal Cancer Study Group and Roche Austria. Dr. Rinnerthaler disclosed relationships with multiple companies including Amgen, Daiichi Sankyo, Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Seagen, and Pierre Fabre. Dr. Lambertini disclosed relationships with multiple companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, MSD, Seagen, Gilead, Takeda, Sandoz, Ipsen, Libbs, Knight, and Daiichi Sankyo.

A single dose of a new antibody-drug conjugate known as patritumab deruxtecan provoked a response in nearly one-third of patients with HR-positive/HER2-negative or triple-negative breast cancer, according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

Heidi Splete/MDedge News

Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.

Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.

Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.

In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.

In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.

Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.

All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.

At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049). 

In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).

Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.

HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.

A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.

To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.

During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
 

ICARUS-BREAST01

In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.

Heidi Splete/MDedge News

The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.

After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.

As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.

Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.

“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.

In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.

Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.

In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.

Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.

Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
 

Early results merit further exploration

Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.

Heidi Splete/MDedge News

“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.

In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.

“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.

The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.

“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”

In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.

The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.

A single dose of a new antibody-drug conjugate known as patritumab deruxtecan provoked a response in nearly one-third of patients with HR-positive/HER2-negative or triple-negative breast cancer, according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

Heidi Splete/MDedge News

Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.

Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.

Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.

In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.

In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.

Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.

All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.

At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049). 

In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).

Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.

HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.

A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.

To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.

During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
 

ICARUS-BREAST01

In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.

Heidi Splete/MDedge News

The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.

After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.

As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.

Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.

“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.

In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.

Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.

In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.

Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.

Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
 

Early results merit further exploration

Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.

Heidi Splete/MDedge News

“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.

In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.

“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.

The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.

“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”

In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.

The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.

A single dose of a new antibody-drug conjugate known as patritumab deruxtecan provoked a response in nearly one-third of patients with HR-positive/HER2-negative or triple-negative breast cancer, according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

Heidi Splete/MDedge News

Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.

Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.

Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.

In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.

In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.

Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.

All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.

At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049). 

In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).

Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.

HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.

A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.

To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.

During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
 

ICARUS-BREAST01

In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.

Heidi Splete/MDedge News

The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.

After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.

As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.

Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.

“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.

In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.

Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.

In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.

Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.

Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
 

Early results merit further exploration

Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.

Heidi Splete/MDedge News

“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.

In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.

“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.

The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.

“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”

In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.

The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.

The Food and Drug Administration has approved the oral medication fezolinetant (Veozah) for the treatment of moderate to severe hot flashes in menopausal women, according to an FDA statement. The approved dose is 45 mg once daily.

Fezolinetant, a neurokinin 3 (NK3) receptor antagonist, is the first drug of its kind to earn FDA approval for the vasomotor symptoms associated with menopause, according to the statement. The drug works by binding to the NK3 receptor, which plays a role in regulating body temperature, and blocking its activity. Fezolinetant is not a hormone, and can be taken by women for whom hormones are contraindicated, such as those with a history of vaginal bleeding, stroke, heart attack, blood clots, or liver disease, the FDA stated.

The approval was based on data from the SKYLIGHT 2 trial, results of which were presented at the annual meeting of the Endocrine Society, reported by this news organization, and published in the Journal of Clinical Endocrinology and Metabolism.

In the two-phase trial, women were randomized to 30 mg or 45 mg of fezolinetant or a placebo. After 12 weeks, women in placebo groups were rerandomized to fezolinetant for a 40-week safety study.

The study population included women aged 40-65 years, with an average minimum of seven moderate-to-severe hot flashes per day. The study included 120 sites in North America and Europe.

At 12 weeks, both placebo and fezolinetant patients experienced reductions in moderate to severe vasomotor symptoms of approximately 60%, as well as a significant decrease in vasomotor symptom severity.

The FDA statement noted that patients should undergo baseline blood work before starting fezolinetant to test for liver infection or damage, and the prescribing information includes a warning for liver injury; blood work should be repeated at 3, 6, and 9 months after starting the medication, according to the FDA and a press release from the manufacturer Astellas.

The most common side effects associated with fezolinetant include abdominal pain, diarrhea, insomnia, back pain, hot flashes, and elevated liver values, according to the FDA statement. The FDA granted Astellas Pharma’s application a Priority Review designation. Astellas has priced the drug at $550 for a 30-day supply, significantly higher than the Institute for Clinical and Economic Review’s previously recommended range of $2,000 to $2,500 per year.

Full prescribing information is available here.

The Food and Drug Administration has approved the oral medication fezolinetant (Veozah) for the treatment of moderate to severe hot flashes in menopausal women, according to an FDA statement. The approved dose is 45 mg once daily.

Fezolinetant, a neurokinin 3 (NK3) receptor antagonist, is the first drug of its kind to earn FDA approval for the vasomotor symptoms associated with menopause, according to the statement. The drug works by binding to the NK3 receptor, which plays a role in regulating body temperature, and blocking its activity. Fezolinetant is not a hormone, and can be taken by women for whom hormones are contraindicated, such as those with a history of vaginal bleeding, stroke, heart attack, blood clots, or liver disease, the FDA stated.

The approval was based on data from the SKYLIGHT 2 trial, results of which were presented at the annual meeting of the Endocrine Society, reported by this news organization, and published in the Journal of Clinical Endocrinology and Metabolism.

In the two-phase trial, women were randomized to 30 mg or 45 mg of fezolinetant or a placebo. After 12 weeks, women in placebo groups were rerandomized to fezolinetant for a 40-week safety study.

The study population included women aged 40-65 years, with an average minimum of seven moderate-to-severe hot flashes per day. The study included 120 sites in North America and Europe.

At 12 weeks, both placebo and fezolinetant patients experienced reductions in moderate to severe vasomotor symptoms of approximately 60%, as well as a significant decrease in vasomotor symptom severity.

The FDA statement noted that patients should undergo baseline blood work before starting fezolinetant to test for liver infection or damage, and the prescribing information includes a warning for liver injury; blood work should be repeated at 3, 6, and 9 months after starting the medication, according to the FDA and a press release from the manufacturer Astellas.

The most common side effects associated with fezolinetant include abdominal pain, diarrhea, insomnia, back pain, hot flashes, and elevated liver values, according to the FDA statement. The FDA granted Astellas Pharma’s application a Priority Review designation. Astellas has priced the drug at $550 for a 30-day supply, significantly higher than the Institute for Clinical and Economic Review’s previously recommended range of $2,000 to $2,500 per year.

Full prescribing information is available here.

The Food and Drug Administration has approved the oral medication fezolinetant (Veozah) for the treatment of moderate to severe hot flashes in menopausal women, according to an FDA statement. The approved dose is 45 mg once daily.

Fezolinetant, a neurokinin 3 (NK3) receptor antagonist, is the first drug of its kind to earn FDA approval for the vasomotor symptoms associated with menopause, according to the statement. The drug works by binding to the NK3 receptor, which plays a role in regulating body temperature, and blocking its activity. Fezolinetant is not a hormone, and can be taken by women for whom hormones are contraindicated, such as those with a history of vaginal bleeding, stroke, heart attack, blood clots, or liver disease, the FDA stated.

The approval was based on data from the SKYLIGHT 2 trial, results of which were presented at the annual meeting of the Endocrine Society, reported by this news organization, and published in the Journal of Clinical Endocrinology and Metabolism.

In the two-phase trial, women were randomized to 30 mg or 45 mg of fezolinetant or a placebo. After 12 weeks, women in placebo groups were rerandomized to fezolinetant for a 40-week safety study.

The study population included women aged 40-65 years, with an average minimum of seven moderate-to-severe hot flashes per day. The study included 120 sites in North America and Europe.

At 12 weeks, both placebo and fezolinetant patients experienced reductions in moderate to severe vasomotor symptoms of approximately 60%, as well as a significant decrease in vasomotor symptom severity.

The FDA statement noted that patients should undergo baseline blood work before starting fezolinetant to test for liver infection or damage, and the prescribing information includes a warning for liver injury; blood work should be repeated at 3, 6, and 9 months after starting the medication, according to the FDA and a press release from the manufacturer Astellas.

The most common side effects associated with fezolinetant include abdominal pain, diarrhea, insomnia, back pain, hot flashes, and elevated liver values, according to the FDA statement. The FDA granted Astellas Pharma’s application a Priority Review designation. Astellas has priced the drug at $550 for a 30-day supply, significantly higher than the Institute for Clinical and Economic Review’s previously recommended range of $2,000 to $2,500 per year.

Full prescribing information is available here.

In postmenopausal women with hormone receptor–positive breast cancer, overweight and obesity were overall predictors of lower disease-free survival, but body mass index had no apparent association with the effect of extended endocrine therapy on disease-free survival, new data suggest.

Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.

Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.

The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.

Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (30 kg/m² or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.

DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).

“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.

In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.

The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.

In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.

When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
 

Data draw attention to quality of life and lifestyle factors

The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.

Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.

Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.

“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.

The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.

In postmenopausal women with hormone receptor–positive breast cancer, overweight and obesity were overall predictors of lower disease-free survival, but body mass index had no apparent association with the effect of extended endocrine therapy on disease-free survival, new data suggest.

Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.

Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.

The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.

Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (30 kg/m² or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.

DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).

“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.

In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.

The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.

In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.

When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
 

Data draw attention to quality of life and lifestyle factors

The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.

Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.

Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.

“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.

The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.

In postmenopausal women with hormone receptor–positive breast cancer, overweight and obesity were overall predictors of lower disease-free survival, but body mass index had no apparent association with the effect of extended endocrine therapy on disease-free survival, new data suggest.

Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.

Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.

The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.

Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (30 kg/m² or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.

DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).

“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.

In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.

The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.

In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.

When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
 

Data draw attention to quality of life and lifestyle factors

The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.

Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.

Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.

“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.

The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.

Adverse neonatal outcomes occurred in 24.9% of women treated for gestational diabetes at less than 20 weeks’ gestation compared to 30.5% of controls treated later or not at all, based on data from nearly 800 women.

Screening and treatment for gestational diabetes are currently recommended at 24-28 weeks’ gestation, with earlier testing recommended for women at increased risk, but the potential benefits of earlier intervention remain debatable, wrote David Simmons, MD, of Western Sydney University, Campbelltown, Australia, and colleagues.

“Until now, there has been complete equipoise over whether to treat hyperglycemia below that of overt diabetes early in pregnancy,” Dr. Simmons said in an interview. The conflicting questions: “Would early treatment reduce the excess deposition of fat on the baby with all of its sequelae; but would early treatment reduce fuel supply to some babies at a critical time and lead to SGA [small for gestational age]?” Dr. Simmons noted.

In a study published in the New England Journal of Medicine, Dr. Simmons and colleagues randomized 406 women aged 18 years and older with singleton pregnancies to immediate treatment for gestational diabetes. Another 396 women were randomized to a control group for deferred treatment or no treatment, based on results of an oral glucose tolerance test at 24-28 weeks’ gestation. All participants had at least one risk factor for hyperglycemia, and met the World Health Organization criteria for gestational diabetes. Women with preexisting diabetes or contraindicating comorbid medical conditions were excluded.

The study had three primary outcomes. The first was a composite of neonatal outcomes including birth before 37 weeks’ gestation, birth weight of 4,500 g or higher, birth trauma, neonatal respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia.

The final sample included 748 women for adverse neonatal outcomes, 750 for pregnancy-related hypertension, and 492 for neonatal lean body mass. The mean age of the participants was 32 years; approximately one-third were white European and another third were South Asian. Overall baseline demographics were similar between the groups, and the initial oral glucose tolerance tests were performed at a mean of 15.6 weeks’ gestation.

Overall, 24.9% of women in the early treatment group experienced an adverse neonatal event vs. 30.5% of controls, for an adjusted risk difference of –5.6% and adjusted relative risk of 0.82.

Notably, in an exploratory subgroup analysis, respiratory distress occurred in 9.8% of infants born to women in the immediate treatment group vs. 17.0% of infants in the control group. “Neonatal respiratory distress was the main driver of the between-group difference observed for the first primary outcome,” the researchers wrote. A prespecified subgroup analysis suggested that the impact of an earlier intervention on adverse neonatal outcomes might be greater among women with a higher glycemic value and those whose oral glucose tolerance tests occurred at less than 14 weeks’ gestation, they noted. Stillbirths or neonatal deaths were similar and infrequent in both groups.

Pregnancy-related hypertension occurred in 10.6% of the immediate-treatment group and 9.9% of the controls group (adjusted risk difference, 0.7%). For the third outcome, the mean neonatal lean body mass was 2.86 g in the immediate-treatment group and 2.91 g for the controls (adjusted mean difference, −0.04 g).

No differences in serious adverse events related to either screening or treatment were noted between the groups.
 

Impact on neonatal outcomes merits further study

Dr. Simmons said that he was surprised by the study findings. “We thought if there was an effect, it would be small, but it isn’t,” he told this publication.

“If you combine the severe adverse outcomes, the perineal trauma and the reduction in days in NICU/special care unit, this is a significant impact on morbidity and likely on cost,” and researchers are currently examining data for cost-effectiveness, he said.

“We did not expect the likely large impact on reducing respiratory distress and perineal trauma,” he noted. “These findings have not been previously reported, perhaps because they were not looked for.” By contrast, “we thought here might be reductions in lower gestational age and cesarean delivery, but there was not,” he added.

The findings were limited by several factors including the nonstandardized approach to gestational diabetes treatment and the use of third-trimester treatment targets that had not been tested in earlier trimesters, the researchers noted. Other limitations included the focus on women already at high risk for hyperglycemia; therefore, the results might not generalize to women not at risk, they wrote.

The current study represents a beginning of answers, with data suggesting that early treatment for gestational diabetes reduces severe adverse pregnancy outcomes, days in NICU/special care unit, and perineal trauma, likely from the first trimester, said Dr. Simmons. However, the findings must be interpreted with caution, as criteria that are too low “might lead to more small babies,” he said. “We look forward to working with others to translate these findings into practice,” he added.

Much more research is needed to answer the many questions prompted by the current study, including who did and did not have complications, Dr. Simmons told this publication. Other studies are needed to collect data on cost-effectiveness, as well as consumer views, especially “different perspectives from different parts of the globe,” he said. Although there is not enough evidence yet to draw conclusions about the role of continuous glucose monitoring (CGM) in managing gestational diabetes, many studies are underway; “we look forward to the results,” of these studies, Dr. Simmons added.
 

Findings support early screening

Gestational diabetes is one of the most common medical complications of pregnancy, and accounts for more than 80% of diabetes-related diagnoses in pregnancy, said Emily Fay, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, in an interview.

“Previous studies have found that women with gestational diabetes are at higher risk in their pregnancy, including higher chance of developing preeclampsia, higher chance of cesarean delivery, and higher risks for their baby, including risk of shoulder dystocia, birth trauma, and jaundice, and higher birth weights,” she said. “Fortunately, studies have also shown that treatment of gestational diabetes helps lower these risks,” she noted. Currently, patients undergo routine screening for gestational diabetes between 24 and 28 weeks of pregnancy, but some who have risk factors for gestational diabetes may have screening in the early part of pregnancy, said Dr. Fay.

The current findings were not surprising overall, said Dr. Fay, who was not involved in the study. “The study authors looked at a variety of outcomes including neonatal adverse outcomes, neonatal body weight, and pregnancy-related hypertension,” she said.

The researchers found that patients treated early had a lower rate of adverse neonatal outcomes, which was to be expected, Dr. Fay said. “They did not find a difference in neonatal body weight; this also was not surprising, as the women who were not in the early treatment group still received treatment at the time of diagnosis later in pregnancy, which likely helped normalize the weights,” she explained.

“My takeaway from this study is that we should continue to screen patients with risk factors for gestational diabetes early in pregnancy and treat them at the time of diagnosis,” Dr. Fay told this publication. However, barriers that may exist to early treatment involve access to care, including being able to see a provider early in pregnancy, she said. “The treatment for gestational diabetes includes dietary education with diet changes and checking blood sugars frequently. Access to nutrition education can be limited and access to healthy foods can be expensive and difficult to obtain,” she noted. “Checking blood sugars throughout the day can also be difficult for those who are busy or working and who may not have the ability to take time to do this,” she said. However, “these barriers may be overcome by health care reform that improves patient access to and coverage of pregnancy care, improved access and affordability of healthy foods, and employer flexibility to allow the time and space to check blood sugars if needed,” she added.

Looking ahead, the use of continuous glucose monitors in pregnancy is an expanding area of research, said Dr. Fay. “Patients can quickly view their blood sugar without the use of finger sticks, which may help overcome some of the barriers patients may have with using finger sticks,” she noted. “Continuous glucose monitors have been used for those with type 1 and type 2 diabetes with success, and we need to better understand if these can also be helpful in gestational diabetes,” she said. Dr. Fay and colleagues at the University of Washington are currently conducting an ongoing study to explore the use of CGM in gestational diabetes.

The study was supported by the National Health and Medical Research Council, the Region Örebro Research Committee, the Medical Scientific Fund of the Mayor of Vienna, the South Western Sydney Local Health District Academic Unit, and a Western Sydney University Ainsworth Trust Grant. The researchers had no financial conflicts to disclose. Dr. Fay had no relevant financial conflicts to disclose.

Adverse neonatal outcomes occurred in 24.9% of women treated for gestational diabetes at less than 20 weeks’ gestation compared to 30.5% of controls treated later or not at all, based on data from nearly 800 women.

Screening and treatment for gestational diabetes are currently recommended at 24-28 weeks’ gestation, with earlier testing recommended for women at increased risk, but the potential benefits of earlier intervention remain debatable, wrote David Simmons, MD, of Western Sydney University, Campbelltown, Australia, and colleagues.

“Until now, there has been complete equipoise over whether to treat hyperglycemia below that of overt diabetes early in pregnancy,” Dr. Simmons said in an interview. The conflicting questions: “Would early treatment reduce the excess deposition of fat on the baby with all of its sequelae; but would early treatment reduce fuel supply to some babies at a critical time and lead to SGA [small for gestational age]?” Dr. Simmons noted.

In a study published in the New England Journal of Medicine, Dr. Simmons and colleagues randomized 406 women aged 18 years and older with singleton pregnancies to immediate treatment for gestational diabetes. Another 396 women were randomized to a control group for deferred treatment or no treatment, based on results of an oral glucose tolerance test at 24-28 weeks’ gestation. All participants had at least one risk factor for hyperglycemia, and met the World Health Organization criteria for gestational diabetes. Women with preexisting diabetes or contraindicating comorbid medical conditions were excluded.

The study had three primary outcomes. The first was a composite of neonatal outcomes including birth before 37 weeks’ gestation, birth weight of 4,500 g or higher, birth trauma, neonatal respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia.

The final sample included 748 women for adverse neonatal outcomes, 750 for pregnancy-related hypertension, and 492 for neonatal lean body mass. The mean age of the participants was 32 years; approximately one-third were white European and another third were South Asian. Overall baseline demographics were similar between the groups, and the initial oral glucose tolerance tests were performed at a mean of 15.6 weeks’ gestation.

Overall, 24.9% of women in the early treatment group experienced an adverse neonatal event vs. 30.5% of controls, for an adjusted risk difference of –5.6% and adjusted relative risk of 0.82.

Notably, in an exploratory subgroup analysis, respiratory distress occurred in 9.8% of infants born to women in the immediate treatment group vs. 17.0% of infants in the control group. “Neonatal respiratory distress was the main driver of the between-group difference observed for the first primary outcome,” the researchers wrote. A prespecified subgroup analysis suggested that the impact of an earlier intervention on adverse neonatal outcomes might be greater among women with a higher glycemic value and those whose oral glucose tolerance tests occurred at less than 14 weeks’ gestation, they noted. Stillbirths or neonatal deaths were similar and infrequent in both groups.

Pregnancy-related hypertension occurred in 10.6% of the immediate-treatment group and 9.9% of the controls group (adjusted risk difference, 0.7%). For the third outcome, the mean neonatal lean body mass was 2.86 g in the immediate-treatment group and 2.91 g for the controls (adjusted mean difference, −0.04 g).

No differences in serious adverse events related to either screening or treatment were noted between the groups.
 

Impact on neonatal outcomes merits further study

Dr. Simmons said that he was surprised by the study findings. “We thought if there was an effect, it would be small, but it isn’t,” he told this publication.

“If you combine the severe adverse outcomes, the perineal trauma and the reduction in days in NICU/special care unit, this is a significant impact on morbidity and likely on cost,” and researchers are currently examining data for cost-effectiveness, he said.

“We did not expect the likely large impact on reducing respiratory distress and perineal trauma,” he noted. “These findings have not been previously reported, perhaps because they were not looked for.” By contrast, “we thought here might be reductions in lower gestational age and cesarean delivery, but there was not,” he added.

The findings were limited by several factors including the nonstandardized approach to gestational diabetes treatment and the use of third-trimester treatment targets that had not been tested in earlier trimesters, the researchers noted. Other limitations included the focus on women already at high risk for hyperglycemia; therefore, the results might not generalize to women not at risk, they wrote.

The current study represents a beginning of answers, with data suggesting that early treatment for gestational diabetes reduces severe adverse pregnancy outcomes, days in NICU/special care unit, and perineal trauma, likely from the first trimester, said Dr. Simmons. However, the findings must be interpreted with caution, as criteria that are too low “might lead to more small babies,” he said. “We look forward to working with others to translate these findings into practice,” he added.

Much more research is needed to answer the many questions prompted by the current study, including who did and did not have complications, Dr. Simmons told this publication. Other studies are needed to collect data on cost-effectiveness, as well as consumer views, especially “different perspectives from different parts of the globe,” he said. Although there is not enough evidence yet to draw conclusions about the role of continuous glucose monitoring (CGM) in managing gestational diabetes, many studies are underway; “we look forward to the results,” of these studies, Dr. Simmons added.
 

Findings support early screening

Gestational diabetes is one of the most common medical complications of pregnancy, and accounts for more than 80% of diabetes-related diagnoses in pregnancy, said Emily Fay, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, in an interview.

“Previous studies have found that women with gestational diabetes are at higher risk in their pregnancy, including higher chance of developing preeclampsia, higher chance of cesarean delivery, and higher risks for their baby, including risk of shoulder dystocia, birth trauma, and jaundice, and higher birth weights,” she said. “Fortunately, studies have also shown that treatment of gestational diabetes helps lower these risks,” she noted. Currently, patients undergo routine screening for gestational diabetes between 24 and 28 weeks of pregnancy, but some who have risk factors for gestational diabetes may have screening in the early part of pregnancy, said Dr. Fay.

The current findings were not surprising overall, said Dr. Fay, who was not involved in the study. “The study authors looked at a variety of outcomes including neonatal adverse outcomes, neonatal body weight, and pregnancy-related hypertension,” she said.

The researchers found that patients treated early had a lower rate of adverse neonatal outcomes, which was to be expected, Dr. Fay said. “They did not find a difference in neonatal body weight; this also was not surprising, as the women who were not in the early treatment group still received treatment at the time of diagnosis later in pregnancy, which likely helped normalize the weights,” she explained.

“My takeaway from this study is that we should continue to screen patients with risk factors for gestational diabetes early in pregnancy and treat them at the time of diagnosis,” Dr. Fay told this publication. However, barriers that may exist to early treatment involve access to care, including being able to see a provider early in pregnancy, she said. “The treatment for gestational diabetes includes dietary education with diet changes and checking blood sugars frequently. Access to nutrition education can be limited and access to healthy foods can be expensive and difficult to obtain,” she noted. “Checking blood sugars throughout the day can also be difficult for those who are busy or working and who may not have the ability to take time to do this,” she said. However, “these barriers may be overcome by health care reform that improves patient access to and coverage of pregnancy care, improved access and affordability of healthy foods, and employer flexibility to allow the time and space to check blood sugars if needed,” she added.

Looking ahead, the use of continuous glucose monitors in pregnancy is an expanding area of research, said Dr. Fay. “Patients can quickly view their blood sugar without the use of finger sticks, which may help overcome some of the barriers patients may have with using finger sticks,” she noted. “Continuous glucose monitors have been used for those with type 1 and type 2 diabetes with success, and we need to better understand if these can also be helpful in gestational diabetes,” she said. Dr. Fay and colleagues at the University of Washington are currently conducting an ongoing study to explore the use of CGM in gestational diabetes.

The study was supported by the National Health and Medical Research Council, the Region Örebro Research Committee, the Medical Scientific Fund of the Mayor of Vienna, the South Western Sydney Local Health District Academic Unit, and a Western Sydney University Ainsworth Trust Grant. The researchers had no financial conflicts to disclose. Dr. Fay had no relevant financial conflicts to disclose.

Adverse neonatal outcomes occurred in 24.9% of women treated for gestational diabetes at less than 20 weeks’ gestation compared to 30.5% of controls treated later or not at all, based on data from nearly 800 women.

Screening and treatment for gestational diabetes are currently recommended at 24-28 weeks’ gestation, with earlier testing recommended for women at increased risk, but the potential benefits of earlier intervention remain debatable, wrote David Simmons, MD, of Western Sydney University, Campbelltown, Australia, and colleagues.

“Until now, there has been complete equipoise over whether to treat hyperglycemia below that of overt diabetes early in pregnancy,” Dr. Simmons said in an interview. The conflicting questions: “Would early treatment reduce the excess deposition of fat on the baby with all of its sequelae; but would early treatment reduce fuel supply to some babies at a critical time and lead to SGA [small for gestational age]?” Dr. Simmons noted.

In a study published in the New England Journal of Medicine, Dr. Simmons and colleagues randomized 406 women aged 18 years and older with singleton pregnancies to immediate treatment for gestational diabetes. Another 396 women were randomized to a control group for deferred treatment or no treatment, based on results of an oral glucose tolerance test at 24-28 weeks’ gestation. All participants had at least one risk factor for hyperglycemia, and met the World Health Organization criteria for gestational diabetes. Women with preexisting diabetes or contraindicating comorbid medical conditions were excluded.

The study had three primary outcomes. The first was a composite of neonatal outcomes including birth before 37 weeks’ gestation, birth weight of 4,500 g or higher, birth trauma, neonatal respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia.

The final sample included 748 women for adverse neonatal outcomes, 750 for pregnancy-related hypertension, and 492 for neonatal lean body mass. The mean age of the participants was 32 years; approximately one-third were white European and another third were South Asian. Overall baseline demographics were similar between the groups, and the initial oral glucose tolerance tests were performed at a mean of 15.6 weeks’ gestation.

Overall, 24.9% of women in the early treatment group experienced an adverse neonatal event vs. 30.5% of controls, for an adjusted risk difference of –5.6% and adjusted relative risk of 0.82.

Notably, in an exploratory subgroup analysis, respiratory distress occurred in 9.8% of infants born to women in the immediate treatment group vs. 17.0% of infants in the control group. “Neonatal respiratory distress was the main driver of the between-group difference observed for the first primary outcome,” the researchers wrote. A prespecified subgroup analysis suggested that the impact of an earlier intervention on adverse neonatal outcomes might be greater among women with a higher glycemic value and those whose oral glucose tolerance tests occurred at less than 14 weeks’ gestation, they noted. Stillbirths or neonatal deaths were similar and infrequent in both groups.

Pregnancy-related hypertension occurred in 10.6% of the immediate-treatment group and 9.9% of the controls group (adjusted risk difference, 0.7%). For the third outcome, the mean neonatal lean body mass was 2.86 g in the immediate-treatment group and 2.91 g for the controls (adjusted mean difference, −0.04 g).

No differences in serious adverse events related to either screening or treatment were noted between the groups.
 

Impact on neonatal outcomes merits further study

Dr. Simmons said that he was surprised by the study findings. “We thought if there was an effect, it would be small, but it isn’t,” he told this publication.

“If you combine the severe adverse outcomes, the perineal trauma and the reduction in days in NICU/special care unit, this is a significant impact on morbidity and likely on cost,” and researchers are currently examining data for cost-effectiveness, he said.

“We did not expect the likely large impact on reducing respiratory distress and perineal trauma,” he noted. “These findings have not been previously reported, perhaps because they were not looked for.” By contrast, “we thought here might be reductions in lower gestational age and cesarean delivery, but there was not,” he added.

The findings were limited by several factors including the nonstandardized approach to gestational diabetes treatment and the use of third-trimester treatment targets that had not been tested in earlier trimesters, the researchers noted. Other limitations included the focus on women already at high risk for hyperglycemia; therefore, the results might not generalize to women not at risk, they wrote.

The current study represents a beginning of answers, with data suggesting that early treatment for gestational diabetes reduces severe adverse pregnancy outcomes, days in NICU/special care unit, and perineal trauma, likely from the first trimester, said Dr. Simmons. However, the findings must be interpreted with caution, as criteria that are too low “might lead to more small babies,” he said. “We look forward to working with others to translate these findings into practice,” he added.

Much more research is needed to answer the many questions prompted by the current study, including who did and did not have complications, Dr. Simmons told this publication. Other studies are needed to collect data on cost-effectiveness, as well as consumer views, especially “different perspectives from different parts of the globe,” he said. Although there is not enough evidence yet to draw conclusions about the role of continuous glucose monitoring (CGM) in managing gestational diabetes, many studies are underway; “we look forward to the results,” of these studies, Dr. Simmons added.
 

Findings support early screening

Gestational diabetes is one of the most common medical complications of pregnancy, and accounts for more than 80% of diabetes-related diagnoses in pregnancy, said Emily Fay, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, in an interview.

“Previous studies have found that women with gestational diabetes are at higher risk in their pregnancy, including higher chance of developing preeclampsia, higher chance of cesarean delivery, and higher risks for their baby, including risk of shoulder dystocia, birth trauma, and jaundice, and higher birth weights,” she said. “Fortunately, studies have also shown that treatment of gestational diabetes helps lower these risks,” she noted. Currently, patients undergo routine screening for gestational diabetes between 24 and 28 weeks of pregnancy, but some who have risk factors for gestational diabetes may have screening in the early part of pregnancy, said Dr. Fay.

The current findings were not surprising overall, said Dr. Fay, who was not involved in the study. “The study authors looked at a variety of outcomes including neonatal adverse outcomes, neonatal body weight, and pregnancy-related hypertension,” she said.

The researchers found that patients treated early had a lower rate of adverse neonatal outcomes, which was to be expected, Dr. Fay said. “They did not find a difference in neonatal body weight; this also was not surprising, as the women who were not in the early treatment group still received treatment at the time of diagnosis later in pregnancy, which likely helped normalize the weights,” she explained.

“My takeaway from this study is that we should continue to screen patients with risk factors for gestational diabetes early in pregnancy and treat them at the time of diagnosis,” Dr. Fay told this publication. However, barriers that may exist to early treatment involve access to care, including being able to see a provider early in pregnancy, she said. “The treatment for gestational diabetes includes dietary education with diet changes and checking blood sugars frequently. Access to nutrition education can be limited and access to healthy foods can be expensive and difficult to obtain,” she noted. “Checking blood sugars throughout the day can also be difficult for those who are busy or working and who may not have the ability to take time to do this,” she said. However, “these barriers may be overcome by health care reform that improves patient access to and coverage of pregnancy care, improved access and affordability of healthy foods, and employer flexibility to allow the time and space to check blood sugars if needed,” she added.

Looking ahead, the use of continuous glucose monitors in pregnancy is an expanding area of research, said Dr. Fay. “Patients can quickly view their blood sugar without the use of finger sticks, which may help overcome some of the barriers patients may have with using finger sticks,” she noted. “Continuous glucose monitors have been used for those with type 1 and type 2 diabetes with success, and we need to better understand if these can also be helpful in gestational diabetes,” she said. Dr. Fay and colleagues at the University of Washington are currently conducting an ongoing study to explore the use of CGM in gestational diabetes.

The study was supported by the National Health and Medical Research Council, the Region Örebro Research Committee, the Medical Scientific Fund of the Mayor of Vienna, the South Western Sydney Local Health District Academic Unit, and a Western Sydney University Ainsworth Trust Grant. The researchers had no financial conflicts to disclose. Dr. Fay had no relevant financial conflicts to disclose.

Adults with cutaneous vasculitis experience a significantly diminished quality of life across physical, symptom, and emotional domains, and its measurement with an organ-specific instrument may catch important disease outcomes better than a generic health-related quality of life index, according to survey responses from participants in the Vasculitis Patient-Powered Research Network (VPPRN).

Although cutaneous vasculitis often causes itching, pain, and ulceration, the impact of the disease on specific health-related quality of life (HRQOL) outcomes has not been systematically assessed, wrote Sarah Mann, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Dermatology, the researchers used the VPPRN to conduct an online survey of adults aged 18 years and older with cutaneous manifestations of vasculitis. The survey was conducted between January 2020 and August 2021.

The primary outcomes of HRQOL were determined using two validated measures. One measured skin-related HRQOL (the Effects of Skin Disease on Quality-of-Life Survey [Skindex-29]), and the other measured general health and well-being (36-Item Short Form Health Survey [SF-36]).

The final analysis included 190 survey responses. The mean age of the respondents was 50.5 years, 84.1% were female, and approximately two-thirds reported a duration of vasculitis of at least 5 years. Respondents’ vasculitides included cutaneous small-vessel vasculitis (14%), IgA vasculitis (6.5%), urticarial vasculitis (8.4%), granulomatosis with polyangiitis (17.6%), microscopic polyangiitis (10.3%), eosinophilic vasculitis (15%), polyarteritis nodosa (3.7%), and other vasculitis types (24.2%).

On the Skindex-29 domains, severely or very severely diminished HRQOL was reported by 77.6% of respondents for emotions, 78.5% for symptoms, 60.7% for functioning, and 75.7% for overall HRQOL.

On the SF-36, the HRQOL was below average on six of eight domains, and approximately half of the patients had summative physical component scores (56%) and mental component scores (52%) below 50.

The HRQOL outcomes of cutaneous vasculitis were worse on the Skindex-29 than the SF-36, the researchers noted. “This discordance may reflect the value of disease or organ-specific measures, which may be able to capture important outcomes of disease even when generic measures do not,” they said.

The study findings were limited by several factors, including the potential lack of generalizability to broader populations of vasculitis patients, the researchers noted. Other limitations included the underrepresentation of male patients and the lack of a disease-specific patient-reported outcome measure, they said.

In addition, “Because half of patients reported having disease which was in remission or mildly active, the study findings may underestimate the true role of active cutaneous vasculitis on HRQOL,” the researchers said.

More studies are needed to assess how HRQOL measures respond to disease treatment and control, the researchers wrote in their discussion. However, the results suggest that cutaneous vasculitis has a significant effect on patients’ perception of their health, as well as on their well-being and symptoms, they said.

The study was supported by the Patient-Centered Outcomes Research Institute and GlaxoSmithKline. Dr. Mann had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including GlaxoSmithKline.

Adults with cutaneous vasculitis experience a significantly diminished quality of life across physical, symptom, and emotional domains, and its measurement with an organ-specific instrument may catch important disease outcomes better than a generic health-related quality of life index, according to survey responses from participants in the Vasculitis Patient-Powered Research Network (VPPRN).

Although cutaneous vasculitis often causes itching, pain, and ulceration, the impact of the disease on specific health-related quality of life (HRQOL) outcomes has not been systematically assessed, wrote Sarah Mann, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Dermatology, the researchers used the VPPRN to conduct an online survey of adults aged 18 years and older with cutaneous manifestations of vasculitis. The survey was conducted between January 2020 and August 2021.

The primary outcomes of HRQOL were determined using two validated measures. One measured skin-related HRQOL (the Effects of Skin Disease on Quality-of-Life Survey [Skindex-29]), and the other measured general health and well-being (36-Item Short Form Health Survey [SF-36]).

The final analysis included 190 survey responses. The mean age of the respondents was 50.5 years, 84.1% were female, and approximately two-thirds reported a duration of vasculitis of at least 5 years. Respondents’ vasculitides included cutaneous small-vessel vasculitis (14%), IgA vasculitis (6.5%), urticarial vasculitis (8.4%), granulomatosis with polyangiitis (17.6%), microscopic polyangiitis (10.3%), eosinophilic vasculitis (15%), polyarteritis nodosa (3.7%), and other vasculitis types (24.2%).

On the Skindex-29 domains, severely or very severely diminished HRQOL was reported by 77.6% of respondents for emotions, 78.5% for symptoms, 60.7% for functioning, and 75.7% for overall HRQOL.

On the SF-36, the HRQOL was below average on six of eight domains, and approximately half of the patients had summative physical component scores (56%) and mental component scores (52%) below 50.

The HRQOL outcomes of cutaneous vasculitis were worse on the Skindex-29 than the SF-36, the researchers noted. “This discordance may reflect the value of disease or organ-specific measures, which may be able to capture important outcomes of disease even when generic measures do not,” they said.

The study findings were limited by several factors, including the potential lack of generalizability to broader populations of vasculitis patients, the researchers noted. Other limitations included the underrepresentation of male patients and the lack of a disease-specific patient-reported outcome measure, they said.

In addition, “Because half of patients reported having disease which was in remission or mildly active, the study findings may underestimate the true role of active cutaneous vasculitis on HRQOL,” the researchers said.

More studies are needed to assess how HRQOL measures respond to disease treatment and control, the researchers wrote in their discussion. However, the results suggest that cutaneous vasculitis has a significant effect on patients’ perception of their health, as well as on their well-being and symptoms, they said.

The study was supported by the Patient-Centered Outcomes Research Institute and GlaxoSmithKline. Dr. Mann had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including GlaxoSmithKline.

Adults with cutaneous vasculitis experience a significantly diminished quality of life across physical, symptom, and emotional domains, and its measurement with an organ-specific instrument may catch important disease outcomes better than a generic health-related quality of life index, according to survey responses from participants in the Vasculitis Patient-Powered Research Network (VPPRN).

Although cutaneous vasculitis often causes itching, pain, and ulceration, the impact of the disease on specific health-related quality of life (HRQOL) outcomes has not been systematically assessed, wrote Sarah Mann, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Dermatology, the researchers used the VPPRN to conduct an online survey of adults aged 18 years and older with cutaneous manifestations of vasculitis. The survey was conducted between January 2020 and August 2021.

The primary outcomes of HRQOL were determined using two validated measures. One measured skin-related HRQOL (the Effects of Skin Disease on Quality-of-Life Survey [Skindex-29]), and the other measured general health and well-being (36-Item Short Form Health Survey [SF-36]).

The final analysis included 190 survey responses. The mean age of the respondents was 50.5 years, 84.1% were female, and approximately two-thirds reported a duration of vasculitis of at least 5 years. Respondents’ vasculitides included cutaneous small-vessel vasculitis (14%), IgA vasculitis (6.5%), urticarial vasculitis (8.4%), granulomatosis with polyangiitis (17.6%), microscopic polyangiitis (10.3%), eosinophilic vasculitis (15%), polyarteritis nodosa (3.7%), and other vasculitis types (24.2%).

On the Skindex-29 domains, severely or very severely diminished HRQOL was reported by 77.6% of respondents for emotions, 78.5% for symptoms, 60.7% for functioning, and 75.7% for overall HRQOL.

On the SF-36, the HRQOL was below average on six of eight domains, and approximately half of the patients had summative physical component scores (56%) and mental component scores (52%) below 50.

The HRQOL outcomes of cutaneous vasculitis were worse on the Skindex-29 than the SF-36, the researchers noted. “This discordance may reflect the value of disease or organ-specific measures, which may be able to capture important outcomes of disease even when generic measures do not,” they said.

The study findings were limited by several factors, including the potential lack of generalizability to broader populations of vasculitis patients, the researchers noted. Other limitations included the underrepresentation of male patients and the lack of a disease-specific patient-reported outcome measure, they said.

In addition, “Because half of patients reported having disease which was in remission or mildly active, the study findings may underestimate the true role of active cutaneous vasculitis on HRQOL,” the researchers said.

More studies are needed to assess how HRQOL measures respond to disease treatment and control, the researchers wrote in their discussion. However, the results suggest that cutaneous vasculitis has a significant effect on patients’ perception of their health, as well as on their well-being and symptoms, they said.

The study was supported by the Patient-Centered Outcomes Research Institute and GlaxoSmithKline. Dr. Mann had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including GlaxoSmithKline.

Use of intravenous immunoglobulin (IVIG) had no apparent effect on the risk of venous thromboembolism (VTE) in adults with dermatomyositis (DM), based on data from more than 400 individuals.

DM has been associated with an increased risk of VTE in previous studies, wrote Elizabeth T. Rotrosen, of Boston University and Brigham and Women’s Hospital, Boston, and colleagues. Although IVIG is often effective for DM patients with recalcitrant disease, it carries a boxed warning for increased thrombosis risk; however, the association between IVIG use and VTE risk in DM has not been well examined, the researchers said.

In a study published in JAMA Dermatology, the researchers identified 458 adults with DM based on the European Alliance of Associations for Reumatology/American College of Rheumatology criteria. The mean age of the participants was 51.8 years, 76% were female, and 82% were White. Of these, 178 were treated with IVIG and 280 were not. The mean duration of IVIG treatment was 32.9 months. The researchers used the chi square test to test for independence between binary variables, the Pearson chi square test to test for independence between categorical variables, and the unpaired t test to compare continuous variables in their statistical analysis.

A total of 23 patients experienced DM-associated VTEs; 6 in the IVIG group and 17 in the non-IVIG group (3.4% vs. 5.7%, P = .20), a nonsignificant difference. The patients in the IVIG group who experienced a DM-associated VTE all underwent IVIG treatment within 4 weeks before the event.

bong hyunjung/iStock/Getty Images

The study findings were limited by several factors, including the retrospective design and small number of VTEs. Prospective studies are needed for better assessment of the VTE risk in patients with DM treated with IVIG, the researchers noted. However, the study is the largest known to explore the association between IVIG use and VTE risk in patients with DM, they said, and the results suggest that clinicians may continue IVIG use in these patients with considerations of risks and benefits on an individual basis.

The study received no outside funding. Ms. Rotrosen had no financial conflicts to disclose. Two coauthors reported financial relationships with Pfizer unrelated to this study.

Use of intravenous immunoglobulin (IVIG) had no apparent effect on the risk of venous thromboembolism (VTE) in adults with dermatomyositis (DM), based on data from more than 400 individuals.

DM has been associated with an increased risk of VTE in previous studies, wrote Elizabeth T. Rotrosen, of Boston University and Brigham and Women’s Hospital, Boston, and colleagues. Although IVIG is often effective for DM patients with recalcitrant disease, it carries a boxed warning for increased thrombosis risk; however, the association between IVIG use and VTE risk in DM has not been well examined, the researchers said.

In a study published in JAMA Dermatology, the researchers identified 458 adults with DM based on the European Alliance of Associations for Reumatology/American College of Rheumatology criteria. The mean age of the participants was 51.8 years, 76% were female, and 82% were White. Of these, 178 were treated with IVIG and 280 were not. The mean duration of IVIG treatment was 32.9 months. The researchers used the chi square test to test for independence between binary variables, the Pearson chi square test to test for independence between categorical variables, and the unpaired t test to compare continuous variables in their statistical analysis.

A total of 23 patients experienced DM-associated VTEs; 6 in the IVIG group and 17 in the non-IVIG group (3.4% vs. 5.7%, P = .20), a nonsignificant difference. The patients in the IVIG group who experienced a DM-associated VTE all underwent IVIG treatment within 4 weeks before the event.

bong hyunjung/iStock/Getty Images

The study findings were limited by several factors, including the retrospective design and small number of VTEs. Prospective studies are needed for better assessment of the VTE risk in patients with DM treated with IVIG, the researchers noted. However, the study is the largest known to explore the association between IVIG use and VTE risk in patients with DM, they said, and the results suggest that clinicians may continue IVIG use in these patients with considerations of risks and benefits on an individual basis.

The study received no outside funding. Ms. Rotrosen had no financial conflicts to disclose. Two coauthors reported financial relationships with Pfizer unrelated to this study.

Use of intravenous immunoglobulin (IVIG) had no apparent effect on the risk of venous thromboembolism (VTE) in adults with dermatomyositis (DM), based on data from more than 400 individuals.

DM has been associated with an increased risk of VTE in previous studies, wrote Elizabeth T. Rotrosen, of Boston University and Brigham and Women’s Hospital, Boston, and colleagues. Although IVIG is often effective for DM patients with recalcitrant disease, it carries a boxed warning for increased thrombosis risk; however, the association between IVIG use and VTE risk in DM has not been well examined, the researchers said.

In a study published in JAMA Dermatology, the researchers identified 458 adults with DM based on the European Alliance of Associations for Reumatology/American College of Rheumatology criteria. The mean age of the participants was 51.8 years, 76% were female, and 82% were White. Of these, 178 were treated with IVIG and 280 were not. The mean duration of IVIG treatment was 32.9 months. The researchers used the chi square test to test for independence between binary variables, the Pearson chi square test to test for independence between categorical variables, and the unpaired t test to compare continuous variables in their statistical analysis.

A total of 23 patients experienced DM-associated VTEs; 6 in the IVIG group and 17 in the non-IVIG group (3.4% vs. 5.7%, P = .20), a nonsignificant difference. The patients in the IVIG group who experienced a DM-associated VTE all underwent IVIG treatment within 4 weeks before the event.

bong hyunjung/iStock/Getty Images

The study findings were limited by several factors, including the retrospective design and small number of VTEs. Prospective studies are needed for better assessment of the VTE risk in patients with DM treated with IVIG, the researchers noted. However, the study is the largest known to explore the association between IVIG use and VTE risk in patients with DM, they said, and the results suggest that clinicians may continue IVIG use in these patients with considerations of risks and benefits on an individual basis.

The study received no outside funding. Ms. Rotrosen had no financial conflicts to disclose. Two coauthors reported financial relationships with Pfizer unrelated to this study.

WASHINGTON – A bundled intervention combining point-of-care testing, electronic medical record support, and provider education significantly improved lipid screening rates in children aged 9-11 years, according to data from approximately 100 monthly visits over a 3-year period.

Guidelines from the National Heart, Lung, and Blood Institute currently recommend universal lipid screening for children aged 9-11 years, but screening rates in clinical practice remain low, according to Ruth E. Gardner, MD, of Penn State University, Hershey, and colleagues.

In a poster presented at the Pediatric Academic Societies annual meeting, Dr. Gardner and colleagues shared results of the implementation of a bundled testing protocol designed to improve screening.

The researchers reviewed data on lipid testing within 30 days for all 9- to 11-year-old well child visits at a single center between May 2019 and February 2022. The bundled intervention was introduced in May 2021.

The bundled protocol included in-office capillary testing and provider education. In addition, electronic medical record templates were modified to include prompts for lipid screening at relevant ages, and EMR orders were adjusted to include lipid testing. The researchers also collected targeted provider feedback on individualized screening rates in February 2022.

Screening rates were plotted monthly. For the period from May 2019 through May 2021, the rates averaged 6.5%. However, after the introduction of the bundled intervention, the rate increased to 29.9%. Following targeted provider feedback in February 2022, the researchers found an additional shift to 52.1% through March and April 2022.

The findings were limited by the use of data from a single center, and the researchers used an extended study period to account for disruptions to well-child care in the spring of 2020 related to the COVID-19 pandemic.

However, the results support the effectiveness of a bundled intervention for improving lipid screening rates in children aged 9-11 years, the researchers said, and targeted provider feedback and education could yield additional improvements, they concluded.
 

Preteen years are an optimal time for screening

“The current study is important because atherosclerosis begins in childhood, and screening at ages 9-11 is an optimal time to begin lifestyle changes to improve overall health and reduce risks of heart disease,” said Margaret Thew, DNP, FNP-BC, of the Medical College of Wisconsin, Milwaukee, in an interview.

Ms. Thew, who was not involved in the study, said, “The number of recommended and required screening items needed in pediatrics is vast, so many providers have to select which items to focus on for their health screenings with these ages.”

Overall, “I was impressed with the improvements that were made in this quality improvement study,” said Ms. Thew.

Barriers to lipid screening in this population include the reduced number of health screenings and immunizations recommended for this age group; the consequence is that access is limited to discuss preventive care opportunities, said Ms. Thew in an interview. Steps to overcome these barriers could include the use of many of the screening tools introduced in the current study, such as point-of-care testing in the office, use of the EMR to remind providers of testing, which can be done during well visits or school physicals, and educating providers about the current guidelines, she noted.

Other strategies to increase screening include moving the immunization series to provide more frequent appointments to children aged 9-11 years to offer education and preventive care, Ms. Thew added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
 

WASHINGTON – A bundled intervention combining point-of-care testing, electronic medical record support, and provider education significantly improved lipid screening rates in children aged 9-11 years, according to data from approximately 100 monthly visits over a 3-year period.

Guidelines from the National Heart, Lung, and Blood Institute currently recommend universal lipid screening for children aged 9-11 years, but screening rates in clinical practice remain low, according to Ruth E. Gardner, MD, of Penn State University, Hershey, and colleagues.

In a poster presented at the Pediatric Academic Societies annual meeting, Dr. Gardner and colleagues shared results of the implementation of a bundled testing protocol designed to improve screening.

The researchers reviewed data on lipid testing within 30 days for all 9- to 11-year-old well child visits at a single center between May 2019 and February 2022. The bundled intervention was introduced in May 2021.

The bundled protocol included in-office capillary testing and provider education. In addition, electronic medical record templates were modified to include prompts for lipid screening at relevant ages, and EMR orders were adjusted to include lipid testing. The researchers also collected targeted provider feedback on individualized screening rates in February 2022.

Screening rates were plotted monthly. For the period from May 2019 through May 2021, the rates averaged 6.5%. However, after the introduction of the bundled intervention, the rate increased to 29.9%. Following targeted provider feedback in February 2022, the researchers found an additional shift to 52.1% through March and April 2022.

The findings were limited by the use of data from a single center, and the researchers used an extended study period to account for disruptions to well-child care in the spring of 2020 related to the COVID-19 pandemic.

However, the results support the effectiveness of a bundled intervention for improving lipid screening rates in children aged 9-11 years, the researchers said, and targeted provider feedback and education could yield additional improvements, they concluded.
 

Preteen years are an optimal time for screening

“The current study is important because atherosclerosis begins in childhood, and screening at ages 9-11 is an optimal time to begin lifestyle changes to improve overall health and reduce risks of heart disease,” said Margaret Thew, DNP, FNP-BC, of the Medical College of Wisconsin, Milwaukee, in an interview.

Ms. Thew, who was not involved in the study, said, “The number of recommended and required screening items needed in pediatrics is vast, so many providers have to select which items to focus on for their health screenings with these ages.”

Overall, “I was impressed with the improvements that were made in this quality improvement study,” said Ms. Thew.

Barriers to lipid screening in this population include the reduced number of health screenings and immunizations recommended for this age group; the consequence is that access is limited to discuss preventive care opportunities, said Ms. Thew in an interview. Steps to overcome these barriers could include the use of many of the screening tools introduced in the current study, such as point-of-care testing in the office, use of the EMR to remind providers of testing, which can be done during well visits or school physicals, and educating providers about the current guidelines, she noted.

Other strategies to increase screening include moving the immunization series to provide more frequent appointments to children aged 9-11 years to offer education and preventive care, Ms. Thew added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
 

WASHINGTON – A bundled intervention combining point-of-care testing, electronic medical record support, and provider education significantly improved lipid screening rates in children aged 9-11 years, according to data from approximately 100 monthly visits over a 3-year period.

Guidelines from the National Heart, Lung, and Blood Institute currently recommend universal lipid screening for children aged 9-11 years, but screening rates in clinical practice remain low, according to Ruth E. Gardner, MD, of Penn State University, Hershey, and colleagues.

In a poster presented at the Pediatric Academic Societies annual meeting, Dr. Gardner and colleagues shared results of the implementation of a bundled testing protocol designed to improve screening.

The researchers reviewed data on lipid testing within 30 days for all 9- to 11-year-old well child visits at a single center between May 2019 and February 2022. The bundled intervention was introduced in May 2021.

The bundled protocol included in-office capillary testing and provider education. In addition, electronic medical record templates were modified to include prompts for lipid screening at relevant ages, and EMR orders were adjusted to include lipid testing. The researchers also collected targeted provider feedback on individualized screening rates in February 2022.

Screening rates were plotted monthly. For the period from May 2019 through May 2021, the rates averaged 6.5%. However, after the introduction of the bundled intervention, the rate increased to 29.9%. Following targeted provider feedback in February 2022, the researchers found an additional shift to 52.1% through March and April 2022.

The findings were limited by the use of data from a single center, and the researchers used an extended study period to account for disruptions to well-child care in the spring of 2020 related to the COVID-19 pandemic.

However, the results support the effectiveness of a bundled intervention for improving lipid screening rates in children aged 9-11 years, the researchers said, and targeted provider feedback and education could yield additional improvements, they concluded.
 

Preteen years are an optimal time for screening

“The current study is important because atherosclerosis begins in childhood, and screening at ages 9-11 is an optimal time to begin lifestyle changes to improve overall health and reduce risks of heart disease,” said Margaret Thew, DNP, FNP-BC, of the Medical College of Wisconsin, Milwaukee, in an interview.

Ms. Thew, who was not involved in the study, said, “The number of recommended and required screening items needed in pediatrics is vast, so many providers have to select which items to focus on for their health screenings with these ages.”

Overall, “I was impressed with the improvements that were made in this quality improvement study,” said Ms. Thew.

Barriers to lipid screening in this population include the reduced number of health screenings and immunizations recommended for this age group; the consequence is that access is limited to discuss preventive care opportunities, said Ms. Thew in an interview. Steps to overcome these barriers could include the use of many of the screening tools introduced in the current study, such as point-of-care testing in the office, use of the EMR to remind providers of testing, which can be done during well visits or school physicals, and educating providers about the current guidelines, she noted.

Other strategies to increase screening include moving the immunization series to provide more frequent appointments to children aged 9-11 years to offer education and preventive care, Ms. Thew added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.