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Do Risk-Reducing Surgeries Benefit BRCA Carriers With Early-Onset Breast Cancer History?
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM SABCS 2024
Special Considerations Needed in Applying Lupus Nephritis Guideline to Children
WASHINGTON — When the American College of Rheumatology (ACR) released its updated guideline for management of lupus nephritis (LN) at its 2024 Annual Meeting, they included recommendations for managing pediatric LN for the first time.
The pediatric recommendations use the same classification criteria, outcome measures, and treatments as in adults — including the first-line triple therapy recommendation — but there remain important differences between pediatric and adult LN, Mary Beth Son, MD, clinical chief of immunology and section chief of rheumatology at Boston Children’s Hospital in Massachusetts, and an associate professor of pediatrics at Harvard Medical School, also in Boston, told attendees.
“In general, kids and adolescents with lupus are sicker,” Son said. They are more likely to have renal manifestations and neuropsychiatric lupus at diagnosis, compared with adults. Further, “although the disease is the same, it’s happening to kids and adolescents who are undergoing critical periods of growth and development.”
Medication risk profiles also shift for younger patients, Son noted.
“Importantly, they’re at risk for higher cumulative dosing of both glucocorticoids and cyclophosphamide,” Son said. “When we give an adolescent a course of cyclophosphamide, we have to be aware that this might be the first of a few courses over the course of the lifetime disease, and with increasing numbers of cyclophosphamide courses, you have increased risk for infertility and malignancy.”
Son also acknowledged challenges of pediatric literature, including differences in definitions of pediatric lupus, very few randomized controlled trials, and fewer pediatric studies in general, with fewer participants. Given these research gaps, the guideline panels included pediatric rheumatologists and nephrologists, and the patient panel included several patients with childhood-onset disease.
Son also addressed differences in pediatric drug development. Dosing studies also do not always directly translate from adults to children because children have larger drug volume distribution and differences in drug clearance, and they may need different formulations, she said. Children tend to tolerate medications better than adults because they usually have fewer comorbidities, but the assessment of a drug’s safety must take its impact on growth and development into consideration.
During a press conference after the session where the guideline was presented, Linda Hiraki, MD, ScD, a clinician-scientist in rheumatology at the Hospital for Sick Children, Toronto, Ontario, Canada, said the panel took into consideration that pediatric patients receive their diagnosis during a critical time of development, so considerations of medication risks include the fact that children “have much more life to live.”
Triple Therapy Recommended
As with adults, the pediatric LN guideline recommends a triple therapy approach: glucocorticoids plus mycophenolate mofetil and belimumab, in addition to the usual renin-angiotensin-aldosterone system inhibitors and hydroxychloroquine. But Son acknowledged limitations of applying the new guideline to children. For one, voclosporin has not been studied in or approved for pediatric patients, although there exists modest evidence for other calcineurin inhibitors, mainly tacrolimus, in children.
“The other important consideration is that the lower dose of prednisone that’s being offered by the guidelines of 40 mg per day as a starting dose has not been studied in pediatric lupus nephritis patients,” Son said. “However, I would offer that, given that we know that kids get higher doses and longer courses, it’s even more important to consider a lower dose to begin with in the setting of other immunosuppressants.”
Good Practice Statements for Pediatric LN
Son also reviewed three good practice statements for pediatric LN. First, “glucocorticoid regimens should use pediatric-appropriate doses for children, as reduction of human glucocorticoid dosing is critically important given the early age of pediatric lupus onset and attendant comorbidities,” she said.
That statement is based on both common sense and some literature, including awareness that children are more likely to receive higher doses of steroids and that children’s higher damage scores are driven in part by steroid-related toxicity, such as avascular necrosis and cataracts. In addition, glucocorticoids can have profound effects on body mass index, mood, and height attainment.
“This is during a period of emerging self-identity and struggles with appearance; steroids exacerbate that” as well as mood issues already associated with puberty, Son said.
The second good practice statement recommends that clinicians monitor patients “for delayed pubertal onset and decreased growth velocity that can result from disease activity and glucocorticoid treatment and consider referral to pediatric endocrinology if indicated.” The third states that “a structured, intentional transition from pediatric to adult rheumatology care is indicated to avoid poor outcomes during this vulnerable period.”
During the press conference, Hiraki said that pediatric rheumatologists already recognize the need for discussions about transfer to adult care to begin very early, even years before patients are ready to transfer.
“The transition from being a pediatric patient to being an adult patient is very challenging for a number of reasons,” starting with loss of insurance coverage, added Bonnie Bermas, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas, Texas. When adult rheumatologists take on these patients, they may not have had care for 2 or 3 years, she said.
Rebecca Sadun, MD, PhD, an associate professor of pediatrics in rheumatology at Duke University School of Medicine, Durham, North Carolina, and vice-chair of the Systemic Lupus Erythematosus Committee for the Childhood Arthritis and Rheumatology Research Alliance, was not involved in the guideline development process but reviewed the new guideline.
“We appreciate that the ACR took care to involve pediatric rheumatologists, pediatric nephrologists, and patients with childhood-onset lupus in the development of the newest lupus nephritis treatment guidelines,” she said in an interview. She also noted, however, that “the dearth of pediatric-specific clinical trial data means that we continue to wonder when it is appropriate to extrapolate from adult data regarding the efficacy, safety, and dosing of certain medications, including steroids and voclosporin.” She also noted that voclosporin use can increase pill burden and therefore be difficult to use in pediatrics.
“Children, adolescents, and young adults are a unique population with unique challenges, including significant struggles with adherence to complex medication regimens,” she said. Sadun drew attention to two themes from the guideline that she found particularly applicable to management of pediatric LN.
“First, we must remain wary of the serious consequences of long-term, high-dose glucocorticoids, and we should continue to look towards steroid-sparing strategies that will reduce reliance on glucocorticoids,” Sadun said. “Second, we are likely to see better outcomes, including better renal response, when we take advantage of combination immunosuppression earlier in the disease course.”
Son, Bermas, and Sadun had no disclosures. Hiraki has consulted for Janssen. The guideline development did not involve outside funding.
A version of this article first appeared on Medscape.com.
WASHINGTON — When the American College of Rheumatology (ACR) released its updated guideline for management of lupus nephritis (LN) at its 2024 Annual Meeting, they included recommendations for managing pediatric LN for the first time.
The pediatric recommendations use the same classification criteria, outcome measures, and treatments as in adults — including the first-line triple therapy recommendation — but there remain important differences between pediatric and adult LN, Mary Beth Son, MD, clinical chief of immunology and section chief of rheumatology at Boston Children’s Hospital in Massachusetts, and an associate professor of pediatrics at Harvard Medical School, also in Boston, told attendees.
“In general, kids and adolescents with lupus are sicker,” Son said. They are more likely to have renal manifestations and neuropsychiatric lupus at diagnosis, compared with adults. Further, “although the disease is the same, it’s happening to kids and adolescents who are undergoing critical periods of growth and development.”
Medication risk profiles also shift for younger patients, Son noted.
“Importantly, they’re at risk for higher cumulative dosing of both glucocorticoids and cyclophosphamide,” Son said. “When we give an adolescent a course of cyclophosphamide, we have to be aware that this might be the first of a few courses over the course of the lifetime disease, and with increasing numbers of cyclophosphamide courses, you have increased risk for infertility and malignancy.”
Son also acknowledged challenges of pediatric literature, including differences in definitions of pediatric lupus, very few randomized controlled trials, and fewer pediatric studies in general, with fewer participants. Given these research gaps, the guideline panels included pediatric rheumatologists and nephrologists, and the patient panel included several patients with childhood-onset disease.
Son also addressed differences in pediatric drug development. Dosing studies also do not always directly translate from adults to children because children have larger drug volume distribution and differences in drug clearance, and they may need different formulations, she said. Children tend to tolerate medications better than adults because they usually have fewer comorbidities, but the assessment of a drug’s safety must take its impact on growth and development into consideration.
During a press conference after the session where the guideline was presented, Linda Hiraki, MD, ScD, a clinician-scientist in rheumatology at the Hospital for Sick Children, Toronto, Ontario, Canada, said the panel took into consideration that pediatric patients receive their diagnosis during a critical time of development, so considerations of medication risks include the fact that children “have much more life to live.”
Triple Therapy Recommended
As with adults, the pediatric LN guideline recommends a triple therapy approach: glucocorticoids plus mycophenolate mofetil and belimumab, in addition to the usual renin-angiotensin-aldosterone system inhibitors and hydroxychloroquine. But Son acknowledged limitations of applying the new guideline to children. For one, voclosporin has not been studied in or approved for pediatric patients, although there exists modest evidence for other calcineurin inhibitors, mainly tacrolimus, in children.
“The other important consideration is that the lower dose of prednisone that’s being offered by the guidelines of 40 mg per day as a starting dose has not been studied in pediatric lupus nephritis patients,” Son said. “However, I would offer that, given that we know that kids get higher doses and longer courses, it’s even more important to consider a lower dose to begin with in the setting of other immunosuppressants.”
Good Practice Statements for Pediatric LN
Son also reviewed three good practice statements for pediatric LN. First, “glucocorticoid regimens should use pediatric-appropriate doses for children, as reduction of human glucocorticoid dosing is critically important given the early age of pediatric lupus onset and attendant comorbidities,” she said.
That statement is based on both common sense and some literature, including awareness that children are more likely to receive higher doses of steroids and that children’s higher damage scores are driven in part by steroid-related toxicity, such as avascular necrosis and cataracts. In addition, glucocorticoids can have profound effects on body mass index, mood, and height attainment.
“This is during a period of emerging self-identity and struggles with appearance; steroids exacerbate that” as well as mood issues already associated with puberty, Son said.
The second good practice statement recommends that clinicians monitor patients “for delayed pubertal onset and decreased growth velocity that can result from disease activity and glucocorticoid treatment and consider referral to pediatric endocrinology if indicated.” The third states that “a structured, intentional transition from pediatric to adult rheumatology care is indicated to avoid poor outcomes during this vulnerable period.”
During the press conference, Hiraki said that pediatric rheumatologists already recognize the need for discussions about transfer to adult care to begin very early, even years before patients are ready to transfer.
“The transition from being a pediatric patient to being an adult patient is very challenging for a number of reasons,” starting with loss of insurance coverage, added Bonnie Bermas, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas, Texas. When adult rheumatologists take on these patients, they may not have had care for 2 or 3 years, she said.
Rebecca Sadun, MD, PhD, an associate professor of pediatrics in rheumatology at Duke University School of Medicine, Durham, North Carolina, and vice-chair of the Systemic Lupus Erythematosus Committee for the Childhood Arthritis and Rheumatology Research Alliance, was not involved in the guideline development process but reviewed the new guideline.
“We appreciate that the ACR took care to involve pediatric rheumatologists, pediatric nephrologists, and patients with childhood-onset lupus in the development of the newest lupus nephritis treatment guidelines,” she said in an interview. She also noted, however, that “the dearth of pediatric-specific clinical trial data means that we continue to wonder when it is appropriate to extrapolate from adult data regarding the efficacy, safety, and dosing of certain medications, including steroids and voclosporin.” She also noted that voclosporin use can increase pill burden and therefore be difficult to use in pediatrics.
“Children, adolescents, and young adults are a unique population with unique challenges, including significant struggles with adherence to complex medication regimens,” she said. Sadun drew attention to two themes from the guideline that she found particularly applicable to management of pediatric LN.
“First, we must remain wary of the serious consequences of long-term, high-dose glucocorticoids, and we should continue to look towards steroid-sparing strategies that will reduce reliance on glucocorticoids,” Sadun said. “Second, we are likely to see better outcomes, including better renal response, when we take advantage of combination immunosuppression earlier in the disease course.”
Son, Bermas, and Sadun had no disclosures. Hiraki has consulted for Janssen. The guideline development did not involve outside funding.
A version of this article first appeared on Medscape.com.
WASHINGTON — When the American College of Rheumatology (ACR) released its updated guideline for management of lupus nephritis (LN) at its 2024 Annual Meeting, they included recommendations for managing pediatric LN for the first time.
The pediatric recommendations use the same classification criteria, outcome measures, and treatments as in adults — including the first-line triple therapy recommendation — but there remain important differences between pediatric and adult LN, Mary Beth Son, MD, clinical chief of immunology and section chief of rheumatology at Boston Children’s Hospital in Massachusetts, and an associate professor of pediatrics at Harvard Medical School, also in Boston, told attendees.
“In general, kids and adolescents with lupus are sicker,” Son said. They are more likely to have renal manifestations and neuropsychiatric lupus at diagnosis, compared with adults. Further, “although the disease is the same, it’s happening to kids and adolescents who are undergoing critical periods of growth and development.”
Medication risk profiles also shift for younger patients, Son noted.
“Importantly, they’re at risk for higher cumulative dosing of both glucocorticoids and cyclophosphamide,” Son said. “When we give an adolescent a course of cyclophosphamide, we have to be aware that this might be the first of a few courses over the course of the lifetime disease, and with increasing numbers of cyclophosphamide courses, you have increased risk for infertility and malignancy.”
Son also acknowledged challenges of pediatric literature, including differences in definitions of pediatric lupus, very few randomized controlled trials, and fewer pediatric studies in general, with fewer participants. Given these research gaps, the guideline panels included pediatric rheumatologists and nephrologists, and the patient panel included several patients with childhood-onset disease.
Son also addressed differences in pediatric drug development. Dosing studies also do not always directly translate from adults to children because children have larger drug volume distribution and differences in drug clearance, and they may need different formulations, she said. Children tend to tolerate medications better than adults because they usually have fewer comorbidities, but the assessment of a drug’s safety must take its impact on growth and development into consideration.
During a press conference after the session where the guideline was presented, Linda Hiraki, MD, ScD, a clinician-scientist in rheumatology at the Hospital for Sick Children, Toronto, Ontario, Canada, said the panel took into consideration that pediatric patients receive their diagnosis during a critical time of development, so considerations of medication risks include the fact that children “have much more life to live.”
Triple Therapy Recommended
As with adults, the pediatric LN guideline recommends a triple therapy approach: glucocorticoids plus mycophenolate mofetil and belimumab, in addition to the usual renin-angiotensin-aldosterone system inhibitors and hydroxychloroquine. But Son acknowledged limitations of applying the new guideline to children. For one, voclosporin has not been studied in or approved for pediatric patients, although there exists modest evidence for other calcineurin inhibitors, mainly tacrolimus, in children.
“The other important consideration is that the lower dose of prednisone that’s being offered by the guidelines of 40 mg per day as a starting dose has not been studied in pediatric lupus nephritis patients,” Son said. “However, I would offer that, given that we know that kids get higher doses and longer courses, it’s even more important to consider a lower dose to begin with in the setting of other immunosuppressants.”
Good Practice Statements for Pediatric LN
Son also reviewed three good practice statements for pediatric LN. First, “glucocorticoid regimens should use pediatric-appropriate doses for children, as reduction of human glucocorticoid dosing is critically important given the early age of pediatric lupus onset and attendant comorbidities,” she said.
That statement is based on both common sense and some literature, including awareness that children are more likely to receive higher doses of steroids and that children’s higher damage scores are driven in part by steroid-related toxicity, such as avascular necrosis and cataracts. In addition, glucocorticoids can have profound effects on body mass index, mood, and height attainment.
“This is during a period of emerging self-identity and struggles with appearance; steroids exacerbate that” as well as mood issues already associated with puberty, Son said.
The second good practice statement recommends that clinicians monitor patients “for delayed pubertal onset and decreased growth velocity that can result from disease activity and glucocorticoid treatment and consider referral to pediatric endocrinology if indicated.” The third states that “a structured, intentional transition from pediatric to adult rheumatology care is indicated to avoid poor outcomes during this vulnerable period.”
During the press conference, Hiraki said that pediatric rheumatologists already recognize the need for discussions about transfer to adult care to begin very early, even years before patients are ready to transfer.
“The transition from being a pediatric patient to being an adult patient is very challenging for a number of reasons,” starting with loss of insurance coverage, added Bonnie Bermas, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas, Texas. When adult rheumatologists take on these patients, they may not have had care for 2 or 3 years, she said.
Rebecca Sadun, MD, PhD, an associate professor of pediatrics in rheumatology at Duke University School of Medicine, Durham, North Carolina, and vice-chair of the Systemic Lupus Erythematosus Committee for the Childhood Arthritis and Rheumatology Research Alliance, was not involved in the guideline development process but reviewed the new guideline.
“We appreciate that the ACR took care to involve pediatric rheumatologists, pediatric nephrologists, and patients with childhood-onset lupus in the development of the newest lupus nephritis treatment guidelines,” she said in an interview. She also noted, however, that “the dearth of pediatric-specific clinical trial data means that we continue to wonder when it is appropriate to extrapolate from adult data regarding the efficacy, safety, and dosing of certain medications, including steroids and voclosporin.” She also noted that voclosporin use can increase pill burden and therefore be difficult to use in pediatrics.
“Children, adolescents, and young adults are a unique population with unique challenges, including significant struggles with adherence to complex medication regimens,” she said. Sadun drew attention to two themes from the guideline that she found particularly applicable to management of pediatric LN.
“First, we must remain wary of the serious consequences of long-term, high-dose glucocorticoids, and we should continue to look towards steroid-sparing strategies that will reduce reliance on glucocorticoids,” Sadun said. “Second, we are likely to see better outcomes, including better renal response, when we take advantage of combination immunosuppression earlier in the disease course.”
Son, Bermas, and Sadun had no disclosures. Hiraki has consulted for Janssen. The guideline development did not involve outside funding.
A version of this article first appeared on Medscape.com.
FROM ACR 2024
Residency to Reality: The Job Outlook for New Docs
Roshan Bransden didn’t count how many job offers she received during her recently completed training in family medicine. “It was pretty nonstop throughout all of my PGY-3 year,” she said.
Most of the job opportunities were different from the type of position she sought or where she wanted to work. Bransden graduated from residency at Montefiore Hospital in New York and accepted a position as a primary care doctor in Miami, close to where she grew up and where her family lives.
More than half (56%) of all residents in AMN Healthcare’s 2023 Survey of Final-Year Medical Residents received 100 or more job solicitations during their training, the highest figure since the survey began more than 30 years ago, the staffing agency reported.
Employers are recruiting residents earlier, offering residency stipends of $1500 to $2500 up to 18 months before they finish their training if they commit to an employment contract, said Leah Grant, president of AMN Healthcare’s Physician Permanent Solutions division, specializing in doctor recruitment. She said that the company’s clients are already eyeing residents completing their training in 2026.
“The key for residents is not about finding a position but choosing the right one out of many.” Grant added that residents typically aren’t taught negotiation skills or how to evaluate job offers. They tend to choose a position based on location, but they should also consider work–life balance issues such as call schedules and whether incentives such as signing bonuses, relocation allowances, and student loan reimbursement offset the job’s time commitment.
“If you are a physician and you are willing to go anywhere, you will have hundreds of opportunities,” said Tibor Nagy, DO, an emergency medicine fellow who recently searched for jobs. “It depends on what they want out of their careers.”
Location Is a Key Consideration
Nagy said he had fewer options because he was limited by location, staying close to where his wife is finishing her internal medicine residency. He is completing his fellowship at Atrium Health Carolinas Medical Center in Charlotte, North Carolina, and preparing to return to Prisma Health in Greenville, South Carolina, where he did his residency.
He said that the job search was easier than he anticipated considering the tight market following a job report from the American College of Emergency Physicians in 2021 that predicted an oversupply of 8000 emergency medicine physicians by 2030.
Halfway through Nagy’s residency, he sought a fellowship in emergency medical services (EMS) to be more competitive in the job market. After that, “Every door I knocked on was open to hiring. Maybe it’s a regional thing. They were happy to interview me.”
In addition to location, Nagy’s top priorities when choosing a job were stability and being able to use his EMS fellowship to become a medical director of an EMS system, agency, or fire department. He wanted to work for a hospital system with an academic focus without much employee turnover.
Salary vs Benefits
AMN Healthcare received the most physician searches for family medicine doctors, followed by OB/GYNs. The staffing agency reported that close to two thirds (63%) of its search engagements during the 2023-2024 review period were for specialists, reflecting the needs of an aging population.
The highest average starting salaries were for surgical and internal medicine subspecialties, according to AMN Healthcare’s 2024 Physician and Advanced Practitioner Recruiting Incentives. Orthopedic surgery averaged $633,000; urology, $540,000; gastroenterology, $506,000; and pulmonary medicine, $418,000. For comparison, the average starting salaries for primary care doctors were family medicine, $255,000; internal medicine, $255,000; and pediatrics, $233,000.
In addition to starting salaries, many physicians receive signing bonuses, relocation allowances, and continuing medical education (CME) allowances. According to the report, the average signing bonus for physicians was $31,473. The average relocation allowance for physicians was $11,284 and the average CME allowance was $3969.
Salary wasn’t Nagy’s top priority when choosing a job, though he admits that the ability to pay back thousands of dollars in medical school loans will be helpful. Instead of focusing on higher pay to offset student loans, Nagy said he sought nonprofit positions to help him qualify for public service loan forgiveness.
The federal program forgives loan balances after the recipient makes monthly payments for 10 years while working for a government or nonprofit organization. He also racked up 3 years of residency and his fellowship year at nonprofit hospitals toward that commitment.
He said jobs that pay more may require doctors to see more patients. “The hustle may be different. There are definitely tradeoffs,” he said.
Bransden said the position she begins in January will allow her to work part-time with full benefits, among other perks. “My employer is a membership-based practice, so I’ll be able to gift a few memberships to family and friends.”
Going Solo
Mohammad Ibrahim, DO, is among a minority of new physicians who have chosen to set up their own practice.
Only 6% of residents in AMN Healthcare’s 2024 report indicated that a solo practice was among their top two choices, while 20% listed partnering with another physician.
Ibrahim is a sports medicine fellow at the University of Michigan Health-West in Wyoming, after finishing his family medicine residency at Trinity Health Livingston Hospital in Howell, Michigan.
After his fellowship ends, he said he plans to stay in Michigan, where his family lives.
Ibrahim said he began his medical education knowing he wanted to become a solo clinician in private practice. He sees it as a way to have more control over his decisions about patient care and business practices.
Working in a hospital often requires doctors to gain approval from several levels of authority for decisions such as ordering new equipment or forgiving part of a service payment. He also wanted to set his schedule to take Friday afternoons off for Muslim prayer.
Although he realizes the challenges of starting a private practice, Ibrahim said those who go through graduate medical education can figure out how to adapt and overcome any obstacles. “I think it’s more doable than we are led to believe.”
He said that if more residents were exposed to private practice, they might pursue that path. During his training, Ibrahim did a rotation with a private practice physician. “It’s nice to see people proud of what they built, what they contributed.”
Most residents don’t choose private practice. In the AMN Healthcare survey, 68% of residents said that employment by a hospital was among their top two choices for a practice setting, 42% said employment by a single-specialty group, and 32%, employment by a multispecialty group.
Of the majority of job searches AMN Healthcare conducted, 28% were to fill positions in hospital settings, followed by 26% for medical groups, 22% for academic medical centers, 13% for urgent care centers and retail clinics, 6% for solo practices, partnerships, or concierge practice settings, and 5% for Federally Qualified Health Centers/Community Health Centers or Indian Health facilities.
Still, the report noted an increase in recruiting for independent medical practice ownership, which dwindled in recent years, with the majority of doctors today employed likely due to financial obstacles of starting a practice.
The increase in recruiting indicates possible renewed interest in these practice settings, particularly concierge medicine, which allows doctors to avoid the challenges of third-party payments, the report stated.
Grant said that despite the flexibility and financial autonomy of starting their own practice, new providers who choose this path face obstacles, such as competing with urgent care centers and retail health clinics, which have been on the rise in the past year.
Saddled with debt from medical training, most graduating residents will choose to work toward financial stability and then consider their own practice later in their career, she said.
Flexible Schedules
Work schedule/call hours or work-life balance was the biggest factor (36%) guiding residents’ choice of first post-residency positions compared with starting salary (19%), according to the Medscape Resident Salary & Debt Report 2024.
Grant said that larger practices and those closer to rural communities tend to offer more innovative work schedules, especially for certain specialists. Some solo practices that form partnerships could potentially allow flexible schedules such as 4-day work weeks or week-on-week-off arrangements, she added.
Physicians are also opting for the flexibility of temporary, locum tenens work to improve job conditions and address feelings of burnout. Dr. Kaydo, DO, as she’s known on Instagram, posts about her experiences as locum tenens. “I found that I could have more flexibility as a locum. I want to be able to take time off when I want and as long as I wanted,” said the full-time family medicine doctor who practices at an outpatient clinic in Philadelphia.
“Basically, I’m contract-working, and they pay me as much as I work, and I can also take more time off.” Her employer for the past year also allowed her to work 10 hours a day, 4 days a week instead of the more traditional 8-hour, 5-day schedule.
Dr. Kaydo said she believes many young doctors think contract employees don’t have a permanent job, are not guaranteed a certain salary, and could easily lose their jobs. “I’ve found that most places really need doctors and are willing to negotiate.”
She said primary care locum doctors are particularly in demand in rural clinics and urban underserved areas.
Nagy said he is considering being a nocturnist, an emergency medicine doctor who works nights, to have more control over his schedule, higher pay, and more flexible shifts. “I switch days and nights and that can be tiring.”
Bransden said job flexibility was her primary job criterion. “I have a young child, so I wanted to work part-time with the potential for even more flexibility down the line. I am working 3 days a week, 8-hour days with a 1-hour break. A 3-day work week came with a pay cut, but for me, it works and is what I need right now.”
A version of this article appeared on Medscape.com.
Roshan Bransden didn’t count how many job offers she received during her recently completed training in family medicine. “It was pretty nonstop throughout all of my PGY-3 year,” she said.
Most of the job opportunities were different from the type of position she sought or where she wanted to work. Bransden graduated from residency at Montefiore Hospital in New York and accepted a position as a primary care doctor in Miami, close to where she grew up and where her family lives.
More than half (56%) of all residents in AMN Healthcare’s 2023 Survey of Final-Year Medical Residents received 100 or more job solicitations during their training, the highest figure since the survey began more than 30 years ago, the staffing agency reported.
Employers are recruiting residents earlier, offering residency stipends of $1500 to $2500 up to 18 months before they finish their training if they commit to an employment contract, said Leah Grant, president of AMN Healthcare’s Physician Permanent Solutions division, specializing in doctor recruitment. She said that the company’s clients are already eyeing residents completing their training in 2026.
“The key for residents is not about finding a position but choosing the right one out of many.” Grant added that residents typically aren’t taught negotiation skills or how to evaluate job offers. They tend to choose a position based on location, but they should also consider work–life balance issues such as call schedules and whether incentives such as signing bonuses, relocation allowances, and student loan reimbursement offset the job’s time commitment.
“If you are a physician and you are willing to go anywhere, you will have hundreds of opportunities,” said Tibor Nagy, DO, an emergency medicine fellow who recently searched for jobs. “It depends on what they want out of their careers.”
Location Is a Key Consideration
Nagy said he had fewer options because he was limited by location, staying close to where his wife is finishing her internal medicine residency. He is completing his fellowship at Atrium Health Carolinas Medical Center in Charlotte, North Carolina, and preparing to return to Prisma Health in Greenville, South Carolina, where he did his residency.
He said that the job search was easier than he anticipated considering the tight market following a job report from the American College of Emergency Physicians in 2021 that predicted an oversupply of 8000 emergency medicine physicians by 2030.
Halfway through Nagy’s residency, he sought a fellowship in emergency medical services (EMS) to be more competitive in the job market. After that, “Every door I knocked on was open to hiring. Maybe it’s a regional thing. They were happy to interview me.”
In addition to location, Nagy’s top priorities when choosing a job were stability and being able to use his EMS fellowship to become a medical director of an EMS system, agency, or fire department. He wanted to work for a hospital system with an academic focus without much employee turnover.
Salary vs Benefits
AMN Healthcare received the most physician searches for family medicine doctors, followed by OB/GYNs. The staffing agency reported that close to two thirds (63%) of its search engagements during the 2023-2024 review period were for specialists, reflecting the needs of an aging population.
The highest average starting salaries were for surgical and internal medicine subspecialties, according to AMN Healthcare’s 2024 Physician and Advanced Practitioner Recruiting Incentives. Orthopedic surgery averaged $633,000; urology, $540,000; gastroenterology, $506,000; and pulmonary medicine, $418,000. For comparison, the average starting salaries for primary care doctors were family medicine, $255,000; internal medicine, $255,000; and pediatrics, $233,000.
In addition to starting salaries, many physicians receive signing bonuses, relocation allowances, and continuing medical education (CME) allowances. According to the report, the average signing bonus for physicians was $31,473. The average relocation allowance for physicians was $11,284 and the average CME allowance was $3969.
Salary wasn’t Nagy’s top priority when choosing a job, though he admits that the ability to pay back thousands of dollars in medical school loans will be helpful. Instead of focusing on higher pay to offset student loans, Nagy said he sought nonprofit positions to help him qualify for public service loan forgiveness.
The federal program forgives loan balances after the recipient makes monthly payments for 10 years while working for a government or nonprofit organization. He also racked up 3 years of residency and his fellowship year at nonprofit hospitals toward that commitment.
He said jobs that pay more may require doctors to see more patients. “The hustle may be different. There are definitely tradeoffs,” he said.
Bransden said the position she begins in January will allow her to work part-time with full benefits, among other perks. “My employer is a membership-based practice, so I’ll be able to gift a few memberships to family and friends.”
Going Solo
Mohammad Ibrahim, DO, is among a minority of new physicians who have chosen to set up their own practice.
Only 6% of residents in AMN Healthcare’s 2024 report indicated that a solo practice was among their top two choices, while 20% listed partnering with another physician.
Ibrahim is a sports medicine fellow at the University of Michigan Health-West in Wyoming, after finishing his family medicine residency at Trinity Health Livingston Hospital in Howell, Michigan.
After his fellowship ends, he said he plans to stay in Michigan, where his family lives.
Ibrahim said he began his medical education knowing he wanted to become a solo clinician in private practice. He sees it as a way to have more control over his decisions about patient care and business practices.
Working in a hospital often requires doctors to gain approval from several levels of authority for decisions such as ordering new equipment or forgiving part of a service payment. He also wanted to set his schedule to take Friday afternoons off for Muslim prayer.
Although he realizes the challenges of starting a private practice, Ibrahim said those who go through graduate medical education can figure out how to adapt and overcome any obstacles. “I think it’s more doable than we are led to believe.”
He said that if more residents were exposed to private practice, they might pursue that path. During his training, Ibrahim did a rotation with a private practice physician. “It’s nice to see people proud of what they built, what they contributed.”
Most residents don’t choose private practice. In the AMN Healthcare survey, 68% of residents said that employment by a hospital was among their top two choices for a practice setting, 42% said employment by a single-specialty group, and 32%, employment by a multispecialty group.
Of the majority of job searches AMN Healthcare conducted, 28% were to fill positions in hospital settings, followed by 26% for medical groups, 22% for academic medical centers, 13% for urgent care centers and retail clinics, 6% for solo practices, partnerships, or concierge practice settings, and 5% for Federally Qualified Health Centers/Community Health Centers or Indian Health facilities.
Still, the report noted an increase in recruiting for independent medical practice ownership, which dwindled in recent years, with the majority of doctors today employed likely due to financial obstacles of starting a practice.
The increase in recruiting indicates possible renewed interest in these practice settings, particularly concierge medicine, which allows doctors to avoid the challenges of third-party payments, the report stated.
Grant said that despite the flexibility and financial autonomy of starting their own practice, new providers who choose this path face obstacles, such as competing with urgent care centers and retail health clinics, which have been on the rise in the past year.
Saddled with debt from medical training, most graduating residents will choose to work toward financial stability and then consider their own practice later in their career, she said.
Flexible Schedules
Work schedule/call hours or work-life balance was the biggest factor (36%) guiding residents’ choice of first post-residency positions compared with starting salary (19%), according to the Medscape Resident Salary & Debt Report 2024.
Grant said that larger practices and those closer to rural communities tend to offer more innovative work schedules, especially for certain specialists. Some solo practices that form partnerships could potentially allow flexible schedules such as 4-day work weeks or week-on-week-off arrangements, she added.
Physicians are also opting for the flexibility of temporary, locum tenens work to improve job conditions and address feelings of burnout. Dr. Kaydo, DO, as she’s known on Instagram, posts about her experiences as locum tenens. “I found that I could have more flexibility as a locum. I want to be able to take time off when I want and as long as I wanted,” said the full-time family medicine doctor who practices at an outpatient clinic in Philadelphia.
“Basically, I’m contract-working, and they pay me as much as I work, and I can also take more time off.” Her employer for the past year also allowed her to work 10 hours a day, 4 days a week instead of the more traditional 8-hour, 5-day schedule.
Dr. Kaydo said she believes many young doctors think contract employees don’t have a permanent job, are not guaranteed a certain salary, and could easily lose their jobs. “I’ve found that most places really need doctors and are willing to negotiate.”
She said primary care locum doctors are particularly in demand in rural clinics and urban underserved areas.
Nagy said he is considering being a nocturnist, an emergency medicine doctor who works nights, to have more control over his schedule, higher pay, and more flexible shifts. “I switch days and nights and that can be tiring.”
Bransden said job flexibility was her primary job criterion. “I have a young child, so I wanted to work part-time with the potential for even more flexibility down the line. I am working 3 days a week, 8-hour days with a 1-hour break. A 3-day work week came with a pay cut, but for me, it works and is what I need right now.”
A version of this article appeared on Medscape.com.
Roshan Bransden didn’t count how many job offers she received during her recently completed training in family medicine. “It was pretty nonstop throughout all of my PGY-3 year,” she said.
Most of the job opportunities were different from the type of position she sought or where she wanted to work. Bransden graduated from residency at Montefiore Hospital in New York and accepted a position as a primary care doctor in Miami, close to where she grew up and where her family lives.
More than half (56%) of all residents in AMN Healthcare’s 2023 Survey of Final-Year Medical Residents received 100 or more job solicitations during their training, the highest figure since the survey began more than 30 years ago, the staffing agency reported.
Employers are recruiting residents earlier, offering residency stipends of $1500 to $2500 up to 18 months before they finish their training if they commit to an employment contract, said Leah Grant, president of AMN Healthcare’s Physician Permanent Solutions division, specializing in doctor recruitment. She said that the company’s clients are already eyeing residents completing their training in 2026.
“The key for residents is not about finding a position but choosing the right one out of many.” Grant added that residents typically aren’t taught negotiation skills or how to evaluate job offers. They tend to choose a position based on location, but they should also consider work–life balance issues such as call schedules and whether incentives such as signing bonuses, relocation allowances, and student loan reimbursement offset the job’s time commitment.
“If you are a physician and you are willing to go anywhere, you will have hundreds of opportunities,” said Tibor Nagy, DO, an emergency medicine fellow who recently searched for jobs. “It depends on what they want out of their careers.”
Location Is a Key Consideration
Nagy said he had fewer options because he was limited by location, staying close to where his wife is finishing her internal medicine residency. He is completing his fellowship at Atrium Health Carolinas Medical Center in Charlotte, North Carolina, and preparing to return to Prisma Health in Greenville, South Carolina, where he did his residency.
He said that the job search was easier than he anticipated considering the tight market following a job report from the American College of Emergency Physicians in 2021 that predicted an oversupply of 8000 emergency medicine physicians by 2030.
Halfway through Nagy’s residency, he sought a fellowship in emergency medical services (EMS) to be more competitive in the job market. After that, “Every door I knocked on was open to hiring. Maybe it’s a regional thing. They were happy to interview me.”
In addition to location, Nagy’s top priorities when choosing a job were stability and being able to use his EMS fellowship to become a medical director of an EMS system, agency, or fire department. He wanted to work for a hospital system with an academic focus without much employee turnover.
Salary vs Benefits
AMN Healthcare received the most physician searches for family medicine doctors, followed by OB/GYNs. The staffing agency reported that close to two thirds (63%) of its search engagements during the 2023-2024 review period were for specialists, reflecting the needs of an aging population.
The highest average starting salaries were for surgical and internal medicine subspecialties, according to AMN Healthcare’s 2024 Physician and Advanced Practitioner Recruiting Incentives. Orthopedic surgery averaged $633,000; urology, $540,000; gastroenterology, $506,000; and pulmonary medicine, $418,000. For comparison, the average starting salaries for primary care doctors were family medicine, $255,000; internal medicine, $255,000; and pediatrics, $233,000.
In addition to starting salaries, many physicians receive signing bonuses, relocation allowances, and continuing medical education (CME) allowances. According to the report, the average signing bonus for physicians was $31,473. The average relocation allowance for physicians was $11,284 and the average CME allowance was $3969.
Salary wasn’t Nagy’s top priority when choosing a job, though he admits that the ability to pay back thousands of dollars in medical school loans will be helpful. Instead of focusing on higher pay to offset student loans, Nagy said he sought nonprofit positions to help him qualify for public service loan forgiveness.
The federal program forgives loan balances after the recipient makes monthly payments for 10 years while working for a government or nonprofit organization. He also racked up 3 years of residency and his fellowship year at nonprofit hospitals toward that commitment.
He said jobs that pay more may require doctors to see more patients. “The hustle may be different. There are definitely tradeoffs,” he said.
Bransden said the position she begins in January will allow her to work part-time with full benefits, among other perks. “My employer is a membership-based practice, so I’ll be able to gift a few memberships to family and friends.”
Going Solo
Mohammad Ibrahim, DO, is among a minority of new physicians who have chosen to set up their own practice.
Only 6% of residents in AMN Healthcare’s 2024 report indicated that a solo practice was among their top two choices, while 20% listed partnering with another physician.
Ibrahim is a sports medicine fellow at the University of Michigan Health-West in Wyoming, after finishing his family medicine residency at Trinity Health Livingston Hospital in Howell, Michigan.
After his fellowship ends, he said he plans to stay in Michigan, where his family lives.
Ibrahim said he began his medical education knowing he wanted to become a solo clinician in private practice. He sees it as a way to have more control over his decisions about patient care and business practices.
Working in a hospital often requires doctors to gain approval from several levels of authority for decisions such as ordering new equipment or forgiving part of a service payment. He also wanted to set his schedule to take Friday afternoons off for Muslim prayer.
Although he realizes the challenges of starting a private practice, Ibrahim said those who go through graduate medical education can figure out how to adapt and overcome any obstacles. “I think it’s more doable than we are led to believe.”
He said that if more residents were exposed to private practice, they might pursue that path. During his training, Ibrahim did a rotation with a private practice physician. “It’s nice to see people proud of what they built, what they contributed.”
Most residents don’t choose private practice. In the AMN Healthcare survey, 68% of residents said that employment by a hospital was among their top two choices for a practice setting, 42% said employment by a single-specialty group, and 32%, employment by a multispecialty group.
Of the majority of job searches AMN Healthcare conducted, 28% were to fill positions in hospital settings, followed by 26% for medical groups, 22% for academic medical centers, 13% for urgent care centers and retail clinics, 6% for solo practices, partnerships, or concierge practice settings, and 5% for Federally Qualified Health Centers/Community Health Centers or Indian Health facilities.
Still, the report noted an increase in recruiting for independent medical practice ownership, which dwindled in recent years, with the majority of doctors today employed likely due to financial obstacles of starting a practice.
The increase in recruiting indicates possible renewed interest in these practice settings, particularly concierge medicine, which allows doctors to avoid the challenges of third-party payments, the report stated.
Grant said that despite the flexibility and financial autonomy of starting their own practice, new providers who choose this path face obstacles, such as competing with urgent care centers and retail health clinics, which have been on the rise in the past year.
Saddled with debt from medical training, most graduating residents will choose to work toward financial stability and then consider their own practice later in their career, she said.
Flexible Schedules
Work schedule/call hours or work-life balance was the biggest factor (36%) guiding residents’ choice of first post-residency positions compared with starting salary (19%), according to the Medscape Resident Salary & Debt Report 2024.
Grant said that larger practices and those closer to rural communities tend to offer more innovative work schedules, especially for certain specialists. Some solo practices that form partnerships could potentially allow flexible schedules such as 4-day work weeks or week-on-week-off arrangements, she added.
Physicians are also opting for the flexibility of temporary, locum tenens work to improve job conditions and address feelings of burnout. Dr. Kaydo, DO, as she’s known on Instagram, posts about her experiences as locum tenens. “I found that I could have more flexibility as a locum. I want to be able to take time off when I want and as long as I wanted,” said the full-time family medicine doctor who practices at an outpatient clinic in Philadelphia.
“Basically, I’m contract-working, and they pay me as much as I work, and I can also take more time off.” Her employer for the past year also allowed her to work 10 hours a day, 4 days a week instead of the more traditional 8-hour, 5-day schedule.
Dr. Kaydo said she believes many young doctors think contract employees don’t have a permanent job, are not guaranteed a certain salary, and could easily lose their jobs. “I’ve found that most places really need doctors and are willing to negotiate.”
She said primary care locum doctors are particularly in demand in rural clinics and urban underserved areas.
Nagy said he is considering being a nocturnist, an emergency medicine doctor who works nights, to have more control over his schedule, higher pay, and more flexible shifts. “I switch days and nights and that can be tiring.”
Bransden said job flexibility was her primary job criterion. “I have a young child, so I wanted to work part-time with the potential for even more flexibility down the line. I am working 3 days a week, 8-hour days with a 1-hour break. A 3-day work week came with a pay cut, but for me, it works and is what I need right now.”
A version of this article appeared on Medscape.com.
Acalabrutinib Combo Promising as Frontline Treatment for CLL
In fit, adult patients without del(17p) or TP53 mutations, the acalabrutinib-venetoclax combination, with or without obinutuzumab, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared with a combination of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab, reported principal investigator Jennifer R. Brown, MD, PhD,who presented the results at the American Society of Hematology (ASH) 2024 Annual Meeting.
Patients with CLL have several frontline treatment options, which include chemoimmunotherapy for low-risk disease as well as venetoclax plus the first-generation BTK inhibitor ibrutinib.
While fixed-duration venetoclax plus ibrutinib can result in deep, durable responses, cardiac toxicity remains a concern, particularly in older patients, explained Brown, director of the CLL Center of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts, during a press conference.
Acalabrutinib is a highly selective second-generation BTK inhibitor with improved safety and tolerability, compared with ibrutinib. Brown and colleagues wanted to see whether this second-generation BTK inhibitor alongside venetoclax provided a clinical benefit and fewer cardiac toxicities as a frontline option in this patient population.
“AMPLIFY provides the first phase 3 evidence of fixed-duration therapy with a combination of venetoclax and a second-generation BTK inhibitor in patients with treatment-naive CLL,” Brown said. And these results “show the promise of a new all-oral fixed-duration therapy approach, which would allow patients to take breaks from treatment, reducing the risk of long-term adverse events and drug resistance,” Brown, also from Harvard Medical School, Boston, added in a press release.
Study Details
AMPLIFY randomized 867 patients (median age, 61 years) to three treatment arms: Acalabrutinib in combination with venetoclax alone (n = 291), acalabrutinib and venetoclax with obinutuzumab (n = 286), or the investigator’s choice of chemoimmunotherapy — a combination of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab (n = 290). The median follow-up was 41 months.
Compared with 66.5% in the chemoimmunotherapy arm, 83.1% of patients in the acalabrutinib-venetoclax arm and 76.5% of the acalabrutinib-venetoclax-obinutuzumab arm reached the primary endpoint of 36-month progression-free survival (hazard ratios [HRs] of 0.65 and 0.42, respectively). Median progression-free survival was not reached in the two acalabrutinib arms, compared with 47.6 months in the chemotherapy arm.
More than half of all participants (58.6%) had unmutated immunoglobulin heavy-chain variable region gene (IGHV) status. In a subgroup analysis, patients on either acalabrutinib regimen experienced a significant improvement in progression-free survival compared with those on chemoimmunotherapy, regardless of IGHV status.
It was “particularly noticeable” in the acalabrutinib-venetoclax-obinutuzumab arm (HR, 0.35) that patients with unmutated IGHV were doing as well as those with mutated IGHV, “suggesting that the addition of obinutuzumab may overcome the adverse impact of unmutated IGHV,” Brown said.
Patients also demonstrated a robust response in both investigational arms with an overall response rate of 92.8% for acalabrutinib-venetoclax and 92.7% for acalabrutinib-venetoclax-obinutuzumab, compared with 75.2% for chemoimmunotherapy (P < .0001 for both).
In addition, compared with chemoimmunotherapy, acalabrutinib-venetoclax was associated with a significant improvement in overall survival (HR, 0.33; 95% CI, 0.18-0.56). Acalabrutinib-venetoclax-obinutuzumab was associated with better overall survival (HR, 0.78), but the findings were not statistically significant.
When considering COVID-19 deaths, overall survival findings were significant for both acalabrutinib regimens, Brown reported.
COVID-19 deaths were observed in 10 patients in the acalabrutinib-venetoclax arm, 25 in the acalabrutinib-venetoclax-obinutuzumab arm, and 21 in the chemoimmunotherapy arm.
In terms of safety, both acalabrutinib treatment regimens demonstrated “tolerable safety profiles with a low incidence of cardiac adverse events typically associated with BTK inhibitors, including atrial fibrillation or hypertension,” she reported.
Any serious adverse events were observed in 24.7% of the acalabrutinib-venetoclax patients, 38.4% of those receiving acalabrutinib-venetoclax-obinutuzumab, and 27.4% on chemoimmunotherapy. Serious adverse events leading to death occurred in 3.4%, 6.0%, and 3.5% of patients in the three groups, respectively, and adverse events leading to death occurred in about 8%, 20%, and 10.8%, respectively, of patients.
The most common adverse event was neutropenia, with grade 3 or higher neutropenia occurring in 32.3% of patients in the acalabrutinib-venetoclax arm and 46.1% in the acalabrutinib-venetoclax-obinutuzumab group, compared with 43.2% of patients with chemoimmunotherapy.
As for cardiac events, 9.3% of patients in the acalabrutinib-venetoclax group experienced an event of any grade compared with 12% in the acalabrutinib-venetoclax-obinutuzumab group and 3.5% in the chemoimmunotherapy group.
To Add or Not to Add Obinutuzumab
Asked how clinicians might decide between the two acalabrutinib regimens, Brown said, “if you add the obinutuzumab, it does add more work for the patient,” and it adds more toxicity.
But, she noted, it might optimize progression-free survival.
“I think when physicians are considering whether to use the two- or the three-drug regimen, they have to take account of the patient in front of them,” Brown said. “The acalabrutinib-venetoclax regimen is a very well-tolerated oral regimen, which is really going to be suitable for anyone, and I think, easy to use in the community.”
The fact that there were more COVID-19 deaths in the obinutuzumab arm, compared with the acalabrutinib-venetoclax arm, suggests more immunosuppression in the three-drug regimen, said session moderator Deborah M. Stephens, DO, associate professor of medicine and director of the Chronic Lymphocytic Leukemia and Richter’s Program at the University of North Carolina School of Medicine in Chapel Hill.
This finding could “call into question whether acalabrutinib-venetoclax may have a better risk/benefit ratio when compared to acalabrutinib-venetoclax-obinutuzumab,” she wrote in an email.
Overall, “AMPLIFY is an important trial, and these data will likely be submitted to the US FDA and regulatory bodies of other involved countries to gain approval of the acalabrutinib + venetoclax +/− obinutuzumab regimen,” Stephens added.
“Notably, this is another in a string of phase 3 trials showing that survival is prolonged with targeted agents compared to chemoimmunotherapy,” indicating that standard chemoimmunotherapy “should be considered obsolete as a control arm for phase 3 studies in the frontline treatment of CLL,” said Stephens.
Alexey Danilov, MD, PhD, another CLL specialist from City of Hope, Duarte, California, who was also presenting at the press conference, said, “I don’t see a full justification to use the acalabrutinib-venetoclax-obinutuzumab regimen across the board in all patients, even though progression-free is better. I do think that, unfortunately, this benefit is offset by increased frequency of adverse events.”
Although it looks like “the majority of patients will be very good candidates for acalabrutinib-venetoclax, with impressive progression-free survival, I think we will still have to define who these patients are,” he added.
However, overall, he was enthusiastic. “This is anticipated to get approval as the first oral doublet front line therapy of CLL, and I think many patients do — in my clinic at least — prefer the idea of finite duration therapy to continuous BTK inhibitors.”
The study was funded by AstraZeneca. Brown disclosed consulting with Acerta/AstraZeneca, Genentech/Roche, AbbVie, and multiple other companies. Danilov disclosed consulting with AstraZeneca, Genentech, AbbVie, among others. Stephens had no relevant disclosures.
A version of this article first appeared on Medscape.com.
In fit, adult patients without del(17p) or TP53 mutations, the acalabrutinib-venetoclax combination, with or without obinutuzumab, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared with a combination of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab, reported principal investigator Jennifer R. Brown, MD, PhD,who presented the results at the American Society of Hematology (ASH) 2024 Annual Meeting.
Patients with CLL have several frontline treatment options, which include chemoimmunotherapy for low-risk disease as well as venetoclax plus the first-generation BTK inhibitor ibrutinib.
While fixed-duration venetoclax plus ibrutinib can result in deep, durable responses, cardiac toxicity remains a concern, particularly in older patients, explained Brown, director of the CLL Center of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts, during a press conference.
Acalabrutinib is a highly selective second-generation BTK inhibitor with improved safety and tolerability, compared with ibrutinib. Brown and colleagues wanted to see whether this second-generation BTK inhibitor alongside venetoclax provided a clinical benefit and fewer cardiac toxicities as a frontline option in this patient population.
“AMPLIFY provides the first phase 3 evidence of fixed-duration therapy with a combination of venetoclax and a second-generation BTK inhibitor in patients with treatment-naive CLL,” Brown said. And these results “show the promise of a new all-oral fixed-duration therapy approach, which would allow patients to take breaks from treatment, reducing the risk of long-term adverse events and drug resistance,” Brown, also from Harvard Medical School, Boston, added in a press release.
Study Details
AMPLIFY randomized 867 patients (median age, 61 years) to three treatment arms: Acalabrutinib in combination with venetoclax alone (n = 291), acalabrutinib and venetoclax with obinutuzumab (n = 286), or the investigator’s choice of chemoimmunotherapy — a combination of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab (n = 290). The median follow-up was 41 months.
Compared with 66.5% in the chemoimmunotherapy arm, 83.1% of patients in the acalabrutinib-venetoclax arm and 76.5% of the acalabrutinib-venetoclax-obinutuzumab arm reached the primary endpoint of 36-month progression-free survival (hazard ratios [HRs] of 0.65 and 0.42, respectively). Median progression-free survival was not reached in the two acalabrutinib arms, compared with 47.6 months in the chemotherapy arm.
More than half of all participants (58.6%) had unmutated immunoglobulin heavy-chain variable region gene (IGHV) status. In a subgroup analysis, patients on either acalabrutinib regimen experienced a significant improvement in progression-free survival compared with those on chemoimmunotherapy, regardless of IGHV status.
It was “particularly noticeable” in the acalabrutinib-venetoclax-obinutuzumab arm (HR, 0.35) that patients with unmutated IGHV were doing as well as those with mutated IGHV, “suggesting that the addition of obinutuzumab may overcome the adverse impact of unmutated IGHV,” Brown said.
Patients also demonstrated a robust response in both investigational arms with an overall response rate of 92.8% for acalabrutinib-venetoclax and 92.7% for acalabrutinib-venetoclax-obinutuzumab, compared with 75.2% for chemoimmunotherapy (P < .0001 for both).
In addition, compared with chemoimmunotherapy, acalabrutinib-venetoclax was associated with a significant improvement in overall survival (HR, 0.33; 95% CI, 0.18-0.56). Acalabrutinib-venetoclax-obinutuzumab was associated with better overall survival (HR, 0.78), but the findings were not statistically significant.
When considering COVID-19 deaths, overall survival findings were significant for both acalabrutinib regimens, Brown reported.
COVID-19 deaths were observed in 10 patients in the acalabrutinib-venetoclax arm, 25 in the acalabrutinib-venetoclax-obinutuzumab arm, and 21 in the chemoimmunotherapy arm.
In terms of safety, both acalabrutinib treatment regimens demonstrated “tolerable safety profiles with a low incidence of cardiac adverse events typically associated with BTK inhibitors, including atrial fibrillation or hypertension,” she reported.
Any serious adverse events were observed in 24.7% of the acalabrutinib-venetoclax patients, 38.4% of those receiving acalabrutinib-venetoclax-obinutuzumab, and 27.4% on chemoimmunotherapy. Serious adverse events leading to death occurred in 3.4%, 6.0%, and 3.5% of patients in the three groups, respectively, and adverse events leading to death occurred in about 8%, 20%, and 10.8%, respectively, of patients.
The most common adverse event was neutropenia, with grade 3 or higher neutropenia occurring in 32.3% of patients in the acalabrutinib-venetoclax arm and 46.1% in the acalabrutinib-venetoclax-obinutuzumab group, compared with 43.2% of patients with chemoimmunotherapy.
As for cardiac events, 9.3% of patients in the acalabrutinib-venetoclax group experienced an event of any grade compared with 12% in the acalabrutinib-venetoclax-obinutuzumab group and 3.5% in the chemoimmunotherapy group.
To Add or Not to Add Obinutuzumab
Asked how clinicians might decide between the two acalabrutinib regimens, Brown said, “if you add the obinutuzumab, it does add more work for the patient,” and it adds more toxicity.
But, she noted, it might optimize progression-free survival.
“I think when physicians are considering whether to use the two- or the three-drug regimen, they have to take account of the patient in front of them,” Brown said. “The acalabrutinib-venetoclax regimen is a very well-tolerated oral regimen, which is really going to be suitable for anyone, and I think, easy to use in the community.”
The fact that there were more COVID-19 deaths in the obinutuzumab arm, compared with the acalabrutinib-venetoclax arm, suggests more immunosuppression in the three-drug regimen, said session moderator Deborah M. Stephens, DO, associate professor of medicine and director of the Chronic Lymphocytic Leukemia and Richter’s Program at the University of North Carolina School of Medicine in Chapel Hill.
This finding could “call into question whether acalabrutinib-venetoclax may have a better risk/benefit ratio when compared to acalabrutinib-venetoclax-obinutuzumab,” she wrote in an email.
Overall, “AMPLIFY is an important trial, and these data will likely be submitted to the US FDA and regulatory bodies of other involved countries to gain approval of the acalabrutinib + venetoclax +/− obinutuzumab regimen,” Stephens added.
“Notably, this is another in a string of phase 3 trials showing that survival is prolonged with targeted agents compared to chemoimmunotherapy,” indicating that standard chemoimmunotherapy “should be considered obsolete as a control arm for phase 3 studies in the frontline treatment of CLL,” said Stephens.
Alexey Danilov, MD, PhD, another CLL specialist from City of Hope, Duarte, California, who was also presenting at the press conference, said, “I don’t see a full justification to use the acalabrutinib-venetoclax-obinutuzumab regimen across the board in all patients, even though progression-free is better. I do think that, unfortunately, this benefit is offset by increased frequency of adverse events.”
Although it looks like “the majority of patients will be very good candidates for acalabrutinib-venetoclax, with impressive progression-free survival, I think we will still have to define who these patients are,” he added.
However, overall, he was enthusiastic. “This is anticipated to get approval as the first oral doublet front line therapy of CLL, and I think many patients do — in my clinic at least — prefer the idea of finite duration therapy to continuous BTK inhibitors.”
The study was funded by AstraZeneca. Brown disclosed consulting with Acerta/AstraZeneca, Genentech/Roche, AbbVie, and multiple other companies. Danilov disclosed consulting with AstraZeneca, Genentech, AbbVie, among others. Stephens had no relevant disclosures.
A version of this article first appeared on Medscape.com.
In fit, adult patients without del(17p) or TP53 mutations, the acalabrutinib-venetoclax combination, with or without obinutuzumab, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared with a combination of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab, reported principal investigator Jennifer R. Brown, MD, PhD,who presented the results at the American Society of Hematology (ASH) 2024 Annual Meeting.
Patients with CLL have several frontline treatment options, which include chemoimmunotherapy for low-risk disease as well as venetoclax plus the first-generation BTK inhibitor ibrutinib.
While fixed-duration venetoclax plus ibrutinib can result in deep, durable responses, cardiac toxicity remains a concern, particularly in older patients, explained Brown, director of the CLL Center of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts, during a press conference.
Acalabrutinib is a highly selective second-generation BTK inhibitor with improved safety and tolerability, compared with ibrutinib. Brown and colleagues wanted to see whether this second-generation BTK inhibitor alongside venetoclax provided a clinical benefit and fewer cardiac toxicities as a frontline option in this patient population.
“AMPLIFY provides the first phase 3 evidence of fixed-duration therapy with a combination of venetoclax and a second-generation BTK inhibitor in patients with treatment-naive CLL,” Brown said. And these results “show the promise of a new all-oral fixed-duration therapy approach, which would allow patients to take breaks from treatment, reducing the risk of long-term adverse events and drug resistance,” Brown, also from Harvard Medical School, Boston, added in a press release.
Study Details
AMPLIFY randomized 867 patients (median age, 61 years) to three treatment arms: Acalabrutinib in combination with venetoclax alone (n = 291), acalabrutinib and venetoclax with obinutuzumab (n = 286), or the investigator’s choice of chemoimmunotherapy — a combination of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab (n = 290). The median follow-up was 41 months.
Compared with 66.5% in the chemoimmunotherapy arm, 83.1% of patients in the acalabrutinib-venetoclax arm and 76.5% of the acalabrutinib-venetoclax-obinutuzumab arm reached the primary endpoint of 36-month progression-free survival (hazard ratios [HRs] of 0.65 and 0.42, respectively). Median progression-free survival was not reached in the two acalabrutinib arms, compared with 47.6 months in the chemotherapy arm.
More than half of all participants (58.6%) had unmutated immunoglobulin heavy-chain variable region gene (IGHV) status. In a subgroup analysis, patients on either acalabrutinib regimen experienced a significant improvement in progression-free survival compared with those on chemoimmunotherapy, regardless of IGHV status.
It was “particularly noticeable” in the acalabrutinib-venetoclax-obinutuzumab arm (HR, 0.35) that patients with unmutated IGHV were doing as well as those with mutated IGHV, “suggesting that the addition of obinutuzumab may overcome the adverse impact of unmutated IGHV,” Brown said.
Patients also demonstrated a robust response in both investigational arms with an overall response rate of 92.8% for acalabrutinib-venetoclax and 92.7% for acalabrutinib-venetoclax-obinutuzumab, compared with 75.2% for chemoimmunotherapy (P < .0001 for both).
In addition, compared with chemoimmunotherapy, acalabrutinib-venetoclax was associated with a significant improvement in overall survival (HR, 0.33; 95% CI, 0.18-0.56). Acalabrutinib-venetoclax-obinutuzumab was associated with better overall survival (HR, 0.78), but the findings were not statistically significant.
When considering COVID-19 deaths, overall survival findings were significant for both acalabrutinib regimens, Brown reported.
COVID-19 deaths were observed in 10 patients in the acalabrutinib-venetoclax arm, 25 in the acalabrutinib-venetoclax-obinutuzumab arm, and 21 in the chemoimmunotherapy arm.
In terms of safety, both acalabrutinib treatment regimens demonstrated “tolerable safety profiles with a low incidence of cardiac adverse events typically associated with BTK inhibitors, including atrial fibrillation or hypertension,” she reported.
Any serious adverse events were observed in 24.7% of the acalabrutinib-venetoclax patients, 38.4% of those receiving acalabrutinib-venetoclax-obinutuzumab, and 27.4% on chemoimmunotherapy. Serious adverse events leading to death occurred in 3.4%, 6.0%, and 3.5% of patients in the three groups, respectively, and adverse events leading to death occurred in about 8%, 20%, and 10.8%, respectively, of patients.
The most common adverse event was neutropenia, with grade 3 or higher neutropenia occurring in 32.3% of patients in the acalabrutinib-venetoclax arm and 46.1% in the acalabrutinib-venetoclax-obinutuzumab group, compared with 43.2% of patients with chemoimmunotherapy.
As for cardiac events, 9.3% of patients in the acalabrutinib-venetoclax group experienced an event of any grade compared with 12% in the acalabrutinib-venetoclax-obinutuzumab group and 3.5% in the chemoimmunotherapy group.
To Add or Not to Add Obinutuzumab
Asked how clinicians might decide between the two acalabrutinib regimens, Brown said, “if you add the obinutuzumab, it does add more work for the patient,” and it adds more toxicity.
But, she noted, it might optimize progression-free survival.
“I think when physicians are considering whether to use the two- or the three-drug regimen, they have to take account of the patient in front of them,” Brown said. “The acalabrutinib-venetoclax regimen is a very well-tolerated oral regimen, which is really going to be suitable for anyone, and I think, easy to use in the community.”
The fact that there were more COVID-19 deaths in the obinutuzumab arm, compared with the acalabrutinib-venetoclax arm, suggests more immunosuppression in the three-drug regimen, said session moderator Deborah M. Stephens, DO, associate professor of medicine and director of the Chronic Lymphocytic Leukemia and Richter’s Program at the University of North Carolina School of Medicine in Chapel Hill.
This finding could “call into question whether acalabrutinib-venetoclax may have a better risk/benefit ratio when compared to acalabrutinib-venetoclax-obinutuzumab,” she wrote in an email.
Overall, “AMPLIFY is an important trial, and these data will likely be submitted to the US FDA and regulatory bodies of other involved countries to gain approval of the acalabrutinib + venetoclax +/− obinutuzumab regimen,” Stephens added.
“Notably, this is another in a string of phase 3 trials showing that survival is prolonged with targeted agents compared to chemoimmunotherapy,” indicating that standard chemoimmunotherapy “should be considered obsolete as a control arm for phase 3 studies in the frontline treatment of CLL,” said Stephens.
Alexey Danilov, MD, PhD, another CLL specialist from City of Hope, Duarte, California, who was also presenting at the press conference, said, “I don’t see a full justification to use the acalabrutinib-venetoclax-obinutuzumab regimen across the board in all patients, even though progression-free is better. I do think that, unfortunately, this benefit is offset by increased frequency of adverse events.”
Although it looks like “the majority of patients will be very good candidates for acalabrutinib-venetoclax, with impressive progression-free survival, I think we will still have to define who these patients are,” he added.
However, overall, he was enthusiastic. “This is anticipated to get approval as the first oral doublet front line therapy of CLL, and I think many patients do — in my clinic at least — prefer the idea of finite duration therapy to continuous BTK inhibitors.”
The study was funded by AstraZeneca. Brown disclosed consulting with Acerta/AstraZeneca, Genentech/Roche, AbbVie, and multiple other companies. Danilov disclosed consulting with AstraZeneca, Genentech, AbbVie, among others. Stephens had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
How Are Patients Managing Intermediate-Risk Prostate Cancer?
TOPLINE:
METHODOLOGY:
- Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
- To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
- Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
- Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.
TAKEAWAY:
- Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
- Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
- Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
- Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.
IN PRACTICE:
“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”
SOURCE:
This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.
LIMITATIONS:
This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.
DISCLOSURES:
This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
- To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
- Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
- Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.
TAKEAWAY:
- Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
- Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
- Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
- Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.
IN PRACTICE:
“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”
SOURCE:
This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.
LIMITATIONS:
This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.
DISCLOSURES:
This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
- To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
- Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
- Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.
TAKEAWAY:
- Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
- Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
- Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
- Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.
IN PRACTICE:
“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”
SOURCE:
This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.
LIMITATIONS:
This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.
DISCLOSURES:
This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
New Cancer Drugs: Do Patients Prefer Faster Access or Clinical Benefit?
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY
Clopidogrel Tops Aspirin Post-PCI, Even in High-Risk Cases
TOPLINE:
The beneficial effect of clopidogrel monotherapy over aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) and remained event free for 6-18 months on dual antiplatelet therapy (DAPT) is consistent, regardless of bleeding risk or PCI complexity, according to a post hoc analysis of the HOST-EXAM trial.
METHODOLOGY:
- The HOST-EXAM Extended study conducted across 37 sites in South Korea included patients who underwent PCI with drug-eluting stents and remained free of clinical events for 6-18 months post-PCI, while receiving DAPT.
- This post hoc analysis of the HOST-EXAM Extended study compared the effectiveness of long-term daily clopidogrel (75 mg) with that of aspirin monotherapy (100 mg) after PCI, according to bleeding risk and procedural complexity in 3974 patients (mean age, 63 years; 75% men) who were followed for up to 5.9 years.
- High bleeding risk was reported in 866 patients, and 849 patients underwent complex PCI.
- Patients were classified into four distinct risk groups: No bleeding risk and noncomplex PCI, no bleeding risk and complex PCI, high bleeding risk and noncomplex PCI, and high bleeding risk and complex PCI.
- The co-primary endpoints were thrombotic composite events (cardiovascular death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and definite/probable stent thrombosis) and any bleeding event.
TAKEAWAY:
- Thrombotic composite events (hazard ratio [HR], 2.15; P < .001) and any bleeding event (HR, 3.64; P < .001) were more frequent in patients with a high bleeding risk than in those without.
- However, there was no difference in the risk for thrombotic composite events or any bleeding event by PCI complexity.
- The long-term benefits of clopidogrel monotherapy over aspirin monotherapy were seen in all patients, regardless of bleeding risks (P for interaction = .38 for thrombotic composite events and P for interaction = .20 for any bleeding event) or PCI complexity (P for interaction = .12 for thrombotic composite events and P for interaction = .62 for any bleeding event).
- The greatest risk reduction in thrombotic composite events with clopidogrel monotherapy occurred in patients with a high bleeding risk who underwent complex PCI (HR, 0.46; P = .03).
IN PRACTICE:
“[In this study], no significant interaction was found between treatment arms and risk groups, denoting that the beneficial impact of clopidogrel monotherapy was consistent regardless of HBR [high bleeding risk] or PCI complexity,” the authors wrote.
SOURCE:
This study was led by Jeehoon Kang, MD, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. It was published online on November 27, 2024, in JAMA Cardiology.
LIMITATIONS:
As this study is a post hoc analysis, the findings should be considered primarily hypothesis generating. This study was conducted exclusively in an East Asian population and may not be generalizable to other ethnic groups. The definitions of high bleeding risk and complex PCI used in this analysis were not prespecified in the study protocol of the HOST-EXAM trial. Certain criteria defining high bleeding risk were not analyzed as they fell under the exclusion criteria of the HOST-EXAM trial or were not recorded in the study case report form.
DISCLOSURES:
This study was supported by grants from the Patient-Centered Clinical Research Coordinating Center and Seoul National University Hospital. One author reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
The beneficial effect of clopidogrel monotherapy over aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) and remained event free for 6-18 months on dual antiplatelet therapy (DAPT) is consistent, regardless of bleeding risk or PCI complexity, according to a post hoc analysis of the HOST-EXAM trial.
METHODOLOGY:
- The HOST-EXAM Extended study conducted across 37 sites in South Korea included patients who underwent PCI with drug-eluting stents and remained free of clinical events for 6-18 months post-PCI, while receiving DAPT.
- This post hoc analysis of the HOST-EXAM Extended study compared the effectiveness of long-term daily clopidogrel (75 mg) with that of aspirin monotherapy (100 mg) after PCI, according to bleeding risk and procedural complexity in 3974 patients (mean age, 63 years; 75% men) who were followed for up to 5.9 years.
- High bleeding risk was reported in 866 patients, and 849 patients underwent complex PCI.
- Patients were classified into four distinct risk groups: No bleeding risk and noncomplex PCI, no bleeding risk and complex PCI, high bleeding risk and noncomplex PCI, and high bleeding risk and complex PCI.
- The co-primary endpoints were thrombotic composite events (cardiovascular death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and definite/probable stent thrombosis) and any bleeding event.
TAKEAWAY:
- Thrombotic composite events (hazard ratio [HR], 2.15; P < .001) and any bleeding event (HR, 3.64; P < .001) were more frequent in patients with a high bleeding risk than in those without.
- However, there was no difference in the risk for thrombotic composite events or any bleeding event by PCI complexity.
- The long-term benefits of clopidogrel monotherapy over aspirin monotherapy were seen in all patients, regardless of bleeding risks (P for interaction = .38 for thrombotic composite events and P for interaction = .20 for any bleeding event) or PCI complexity (P for interaction = .12 for thrombotic composite events and P for interaction = .62 for any bleeding event).
- The greatest risk reduction in thrombotic composite events with clopidogrel monotherapy occurred in patients with a high bleeding risk who underwent complex PCI (HR, 0.46; P = .03).
IN PRACTICE:
“[In this study], no significant interaction was found between treatment arms and risk groups, denoting that the beneficial impact of clopidogrel monotherapy was consistent regardless of HBR [high bleeding risk] or PCI complexity,” the authors wrote.
SOURCE:
This study was led by Jeehoon Kang, MD, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. It was published online on November 27, 2024, in JAMA Cardiology.
LIMITATIONS:
As this study is a post hoc analysis, the findings should be considered primarily hypothesis generating. This study was conducted exclusively in an East Asian population and may not be generalizable to other ethnic groups. The definitions of high bleeding risk and complex PCI used in this analysis were not prespecified in the study protocol of the HOST-EXAM trial. Certain criteria defining high bleeding risk were not analyzed as they fell under the exclusion criteria of the HOST-EXAM trial or were not recorded in the study case report form.
DISCLOSURES:
This study was supported by grants from the Patient-Centered Clinical Research Coordinating Center and Seoul National University Hospital. One author reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
The beneficial effect of clopidogrel monotherapy over aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) and remained event free for 6-18 months on dual antiplatelet therapy (DAPT) is consistent, regardless of bleeding risk or PCI complexity, according to a post hoc analysis of the HOST-EXAM trial.
METHODOLOGY:
- The HOST-EXAM Extended study conducted across 37 sites in South Korea included patients who underwent PCI with drug-eluting stents and remained free of clinical events for 6-18 months post-PCI, while receiving DAPT.
- This post hoc analysis of the HOST-EXAM Extended study compared the effectiveness of long-term daily clopidogrel (75 mg) with that of aspirin monotherapy (100 mg) after PCI, according to bleeding risk and procedural complexity in 3974 patients (mean age, 63 years; 75% men) who were followed for up to 5.9 years.
- High bleeding risk was reported in 866 patients, and 849 patients underwent complex PCI.
- Patients were classified into four distinct risk groups: No bleeding risk and noncomplex PCI, no bleeding risk and complex PCI, high bleeding risk and noncomplex PCI, and high bleeding risk and complex PCI.
- The co-primary endpoints were thrombotic composite events (cardiovascular death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and definite/probable stent thrombosis) and any bleeding event.
TAKEAWAY:
- Thrombotic composite events (hazard ratio [HR], 2.15; P < .001) and any bleeding event (HR, 3.64; P < .001) were more frequent in patients with a high bleeding risk than in those without.
- However, there was no difference in the risk for thrombotic composite events or any bleeding event by PCI complexity.
- The long-term benefits of clopidogrel monotherapy over aspirin monotherapy were seen in all patients, regardless of bleeding risks (P for interaction = .38 for thrombotic composite events and P for interaction = .20 for any bleeding event) or PCI complexity (P for interaction = .12 for thrombotic composite events and P for interaction = .62 for any bleeding event).
- The greatest risk reduction in thrombotic composite events with clopidogrel monotherapy occurred in patients with a high bleeding risk who underwent complex PCI (HR, 0.46; P = .03).
IN PRACTICE:
“[In this study], no significant interaction was found between treatment arms and risk groups, denoting that the beneficial impact of clopidogrel monotherapy was consistent regardless of HBR [high bleeding risk] or PCI complexity,” the authors wrote.
SOURCE:
This study was led by Jeehoon Kang, MD, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. It was published online on November 27, 2024, in JAMA Cardiology.
LIMITATIONS:
As this study is a post hoc analysis, the findings should be considered primarily hypothesis generating. This study was conducted exclusively in an East Asian population and may not be generalizable to other ethnic groups. The definitions of high bleeding risk and complex PCI used in this analysis were not prespecified in the study protocol of the HOST-EXAM trial. Certain criteria defining high bleeding risk were not analyzed as they fell under the exclusion criteria of the HOST-EXAM trial or were not recorded in the study case report form.
DISCLOSURES:
This study was supported by grants from the Patient-Centered Clinical Research Coordinating Center and Seoul National University Hospital. One author reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
High-Volume Burn Resuscitation Increases Neurologic Risk
TOPLINE:
METHODOLOGY:
- Researchers conducted a single-center review of 5176 patients with burn injuries who were admitted to a verified American Burn Association center (2003-2017); 622 of them underwent head CT within 96 hours of admission, and 83 showed intracranial abnormalities.
- Of 42 patients (mean age, 49.7 years; 80.5% men) who were admitted within 24 hours of burn, 30 patients received < 200 mL/kg and 11 received > 200 mL/kg of total resuscitation fluids, with a median total body surface area (TBSA) of 20.0.
- The primary outcome assessed was the worsening of neurologic findings on imaging related to the volume of the resuscitation fluid administered; the secondary outcomes were the incidence of new or worsening intracranial abnormalities, including hemorrhage, edema, ischemia, or infarction.
TAKEAWAY:
- Neurologic findings worsened in 47.6% patients receiving < 200 mL/kg of fluid resuscitation and 85.7% of those receiving > 200 mL/kg (P =.064).
- Repeat imaging was performed in 21 (70.0%) patients receiving < 200 mL/kg and 7 (63.6%) patients receiving > 200 mL/kg of resuscitation who underwent follow-up imaging.
- The median TBSA was 16.5 in the < 200 mL/kg group and 53.2 in the > 200 mL/kg group (P <.001).
- Intracranial abnormalities were found in 31.3% patients with hemorrhage, 18.8% with worsening edema, and 43.8% with ischemia or infarction.
IN PRACTICE:
“Patients who received over 200 mL/kg of resuscitation had an increased progression of intracranial abnormalities when compared with patients receiving less volume resuscitation,” the authors wrote. “Neurologic changes prompting imaging in burn patients may be undetectable, and our study further highlights the need for routine evaluation with neurologic imaging when undergoing large-volume resuscitations.”
SOURCE:
The study was led by Connor L. Kenney, MD, Brooke Army Medical Center, San Antonio, and was published online on November 07, 2024, in the Journal of Surgical Research.
LIMITATIONS:
Study limitations included a small patient sample and unclear guidelines for obtaining head CT scans, making it difficult to distinguish between trauma-related brain changes and disease progression. Additionally, the study lacked data on hypotensive episodes and long-term neurologic outcomes.
DISCLOSURES:
This study did not receive any specific funding. The authors declared no conflicts of interest.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a single-center review of 5176 patients with burn injuries who were admitted to a verified American Burn Association center (2003-2017); 622 of them underwent head CT within 96 hours of admission, and 83 showed intracranial abnormalities.
- Of 42 patients (mean age, 49.7 years; 80.5% men) who were admitted within 24 hours of burn, 30 patients received < 200 mL/kg and 11 received > 200 mL/kg of total resuscitation fluids, with a median total body surface area (TBSA) of 20.0.
- The primary outcome assessed was the worsening of neurologic findings on imaging related to the volume of the resuscitation fluid administered; the secondary outcomes were the incidence of new or worsening intracranial abnormalities, including hemorrhage, edema, ischemia, or infarction.
TAKEAWAY:
- Neurologic findings worsened in 47.6% patients receiving < 200 mL/kg of fluid resuscitation and 85.7% of those receiving > 200 mL/kg (P =.064).
- Repeat imaging was performed in 21 (70.0%) patients receiving < 200 mL/kg and 7 (63.6%) patients receiving > 200 mL/kg of resuscitation who underwent follow-up imaging.
- The median TBSA was 16.5 in the < 200 mL/kg group and 53.2 in the > 200 mL/kg group (P <.001).
- Intracranial abnormalities were found in 31.3% patients with hemorrhage, 18.8% with worsening edema, and 43.8% with ischemia or infarction.
IN PRACTICE:
“Patients who received over 200 mL/kg of resuscitation had an increased progression of intracranial abnormalities when compared with patients receiving less volume resuscitation,” the authors wrote. “Neurologic changes prompting imaging in burn patients may be undetectable, and our study further highlights the need for routine evaluation with neurologic imaging when undergoing large-volume resuscitations.”
SOURCE:
The study was led by Connor L. Kenney, MD, Brooke Army Medical Center, San Antonio, and was published online on November 07, 2024, in the Journal of Surgical Research.
LIMITATIONS:
Study limitations included a small patient sample and unclear guidelines for obtaining head CT scans, making it difficult to distinguish between trauma-related brain changes and disease progression. Additionally, the study lacked data on hypotensive episodes and long-term neurologic outcomes.
DISCLOSURES:
This study did not receive any specific funding. The authors declared no conflicts of interest.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a single-center review of 5176 patients with burn injuries who were admitted to a verified American Burn Association center (2003-2017); 622 of them underwent head CT within 96 hours of admission, and 83 showed intracranial abnormalities.
- Of 42 patients (mean age, 49.7 years; 80.5% men) who were admitted within 24 hours of burn, 30 patients received < 200 mL/kg and 11 received > 200 mL/kg of total resuscitation fluids, with a median total body surface area (TBSA) of 20.0.
- The primary outcome assessed was the worsening of neurologic findings on imaging related to the volume of the resuscitation fluid administered; the secondary outcomes were the incidence of new or worsening intracranial abnormalities, including hemorrhage, edema, ischemia, or infarction.
TAKEAWAY:
- Neurologic findings worsened in 47.6% patients receiving < 200 mL/kg of fluid resuscitation and 85.7% of those receiving > 200 mL/kg (P =.064).
- Repeat imaging was performed in 21 (70.0%) patients receiving < 200 mL/kg and 7 (63.6%) patients receiving > 200 mL/kg of resuscitation who underwent follow-up imaging.
- The median TBSA was 16.5 in the < 200 mL/kg group and 53.2 in the > 200 mL/kg group (P <.001).
- Intracranial abnormalities were found in 31.3% patients with hemorrhage, 18.8% with worsening edema, and 43.8% with ischemia or infarction.
IN PRACTICE:
“Patients who received over 200 mL/kg of resuscitation had an increased progression of intracranial abnormalities when compared with patients receiving less volume resuscitation,” the authors wrote. “Neurologic changes prompting imaging in burn patients may be undetectable, and our study further highlights the need for routine evaluation with neurologic imaging when undergoing large-volume resuscitations.”
SOURCE:
The study was led by Connor L. Kenney, MD, Brooke Army Medical Center, San Antonio, and was published online on November 07, 2024, in the Journal of Surgical Research.
LIMITATIONS:
Study limitations included a small patient sample and unclear guidelines for obtaining head CT scans, making it difficult to distinguish between trauma-related brain changes and disease progression. Additionally, the study lacked data on hypotensive episodes and long-term neurologic outcomes.
DISCLOSURES:
This study did not receive any specific funding. The authors declared no conflicts of interest.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Australia Registry Study: Melanoma-Related Deaths Increase at 0.8-mm Breslow Thickness
TOPLINE:
in an Australian study that used registry data.
METHODOLOGY:
- The study analyzed 144,447 individuals (median age, 56 years, 54% men) diagnosed with thin (T1) primary invasive melanomas (Breslow thickness, ≤ 1.0 mm) between 1982 and 2014 from all eight Australian state and territory population-based cancer registries.
- The researchers evaluated the associations between Breslow thickness (< 0.8 mm vs 0.8-1.0 mm) and incidences of melanoma-related and nonmelanoma-related deaths.
- The primary endpoint was time to death attributable to a melanoma-related cause, with death by a nonmelanoma-related cause as a competing event.
TAKEAWAY:
- The 20-year cumulative incidence of melanoma-related deaths was 6.3% for the whole cohort. The incidence was higher for tumors with a thickness of 0.8-1.0 mm (11%) than for those with a thickness < 0.8 mm (5.6%).
- The overall 20-year melanoma-specific survival rate was 95.9%, with rates of 94.2% for tumors < 0.8 mm and 87.8% for tumors measuring 0.8-1.0 mm in thickness. Each 0.1-mm increase in Breslow thickness was associated with worse prognosis.
- A multivariable analysis revealed that a tumor thickness of 0.8-1.0 mm was associated with both a greater absolute risk for melanoma-related deaths (subdistribution hazard ratio, 2.92) and a higher rate of melanoma-related deaths (hazard ratio, 2.98) than a tumor thickness < 0.8 mm.
- The 20-year incidence of death from nonmelanoma-related causes was 23.4%, but the risk for death from these causes showed no significant association with Breslow thickness categories.
IN PRACTICE:
“The findings of this large-scale population–based analysis suggest the separation of risk for patients with melanomas with a Breslow thickness above and below 0.8 mm,” the authors wrote, adding: “These results suggest that a change of the T1 threshold from 1.0 mm to 0.8 mm should be considered when the AJCC [American Joint Committee on Cancer] staging system is next reviewed.”
SOURCE:
The study was led by Serigne N. Lo, PhD, Melanoma Institute Australia, the University of Sydney. It was published online on December 11, 2024, in JAMA Dermatology.
LIMITATIONS:
The study was registry-based and did not capture details such as tumor characteristics and treatment modalities. Inaccuracies in reporting the cause of death may have led to an underestimation of melanoma-specific mortality risks across all thickness groups and an overestimation of nonmelanoma mortality risks.
DISCLOSURES:
The study received funding support from Melanoma Institute Australia and two grants from the Australian National Health and Medical Research Council (NHMRC). Several authors reported receiving grants or personal fees from or having ties with various sources, including NHMRC.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
in an Australian study that used registry data.
METHODOLOGY:
- The study analyzed 144,447 individuals (median age, 56 years, 54% men) diagnosed with thin (T1) primary invasive melanomas (Breslow thickness, ≤ 1.0 mm) between 1982 and 2014 from all eight Australian state and territory population-based cancer registries.
- The researchers evaluated the associations between Breslow thickness (< 0.8 mm vs 0.8-1.0 mm) and incidences of melanoma-related and nonmelanoma-related deaths.
- The primary endpoint was time to death attributable to a melanoma-related cause, with death by a nonmelanoma-related cause as a competing event.
TAKEAWAY:
- The 20-year cumulative incidence of melanoma-related deaths was 6.3% for the whole cohort. The incidence was higher for tumors with a thickness of 0.8-1.0 mm (11%) than for those with a thickness < 0.8 mm (5.6%).
- The overall 20-year melanoma-specific survival rate was 95.9%, with rates of 94.2% for tumors < 0.8 mm and 87.8% for tumors measuring 0.8-1.0 mm in thickness. Each 0.1-mm increase in Breslow thickness was associated with worse prognosis.
- A multivariable analysis revealed that a tumor thickness of 0.8-1.0 mm was associated with both a greater absolute risk for melanoma-related deaths (subdistribution hazard ratio, 2.92) and a higher rate of melanoma-related deaths (hazard ratio, 2.98) than a tumor thickness < 0.8 mm.
- The 20-year incidence of death from nonmelanoma-related causes was 23.4%, but the risk for death from these causes showed no significant association with Breslow thickness categories.
IN PRACTICE:
“The findings of this large-scale population–based analysis suggest the separation of risk for patients with melanomas with a Breslow thickness above and below 0.8 mm,” the authors wrote, adding: “These results suggest that a change of the T1 threshold from 1.0 mm to 0.8 mm should be considered when the AJCC [American Joint Committee on Cancer] staging system is next reviewed.”
SOURCE:
The study was led by Serigne N. Lo, PhD, Melanoma Institute Australia, the University of Sydney. It was published online on December 11, 2024, in JAMA Dermatology.
LIMITATIONS:
The study was registry-based and did not capture details such as tumor characteristics and treatment modalities. Inaccuracies in reporting the cause of death may have led to an underestimation of melanoma-specific mortality risks across all thickness groups and an overestimation of nonmelanoma mortality risks.
DISCLOSURES:
The study received funding support from Melanoma Institute Australia and two grants from the Australian National Health and Medical Research Council (NHMRC). Several authors reported receiving grants or personal fees from or having ties with various sources, including NHMRC.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
in an Australian study that used registry data.
METHODOLOGY:
- The study analyzed 144,447 individuals (median age, 56 years, 54% men) diagnosed with thin (T1) primary invasive melanomas (Breslow thickness, ≤ 1.0 mm) between 1982 and 2014 from all eight Australian state and territory population-based cancer registries.
- The researchers evaluated the associations between Breslow thickness (< 0.8 mm vs 0.8-1.0 mm) and incidences of melanoma-related and nonmelanoma-related deaths.
- The primary endpoint was time to death attributable to a melanoma-related cause, with death by a nonmelanoma-related cause as a competing event.
TAKEAWAY:
- The 20-year cumulative incidence of melanoma-related deaths was 6.3% for the whole cohort. The incidence was higher for tumors with a thickness of 0.8-1.0 mm (11%) than for those with a thickness < 0.8 mm (5.6%).
- The overall 20-year melanoma-specific survival rate was 95.9%, with rates of 94.2% for tumors < 0.8 mm and 87.8% for tumors measuring 0.8-1.0 mm in thickness. Each 0.1-mm increase in Breslow thickness was associated with worse prognosis.
- A multivariable analysis revealed that a tumor thickness of 0.8-1.0 mm was associated with both a greater absolute risk for melanoma-related deaths (subdistribution hazard ratio, 2.92) and a higher rate of melanoma-related deaths (hazard ratio, 2.98) than a tumor thickness < 0.8 mm.
- The 20-year incidence of death from nonmelanoma-related causes was 23.4%, but the risk for death from these causes showed no significant association with Breslow thickness categories.
IN PRACTICE:
“The findings of this large-scale population–based analysis suggest the separation of risk for patients with melanomas with a Breslow thickness above and below 0.8 mm,” the authors wrote, adding: “These results suggest that a change of the T1 threshold from 1.0 mm to 0.8 mm should be considered when the AJCC [American Joint Committee on Cancer] staging system is next reviewed.”
SOURCE:
The study was led by Serigne N. Lo, PhD, Melanoma Institute Australia, the University of Sydney. It was published online on December 11, 2024, in JAMA Dermatology.
LIMITATIONS:
The study was registry-based and did not capture details such as tumor characteristics and treatment modalities. Inaccuracies in reporting the cause of death may have led to an underestimation of melanoma-specific mortality risks across all thickness groups and an overestimation of nonmelanoma mortality risks.
DISCLOSURES:
The study received funding support from Melanoma Institute Australia and two grants from the Australian National Health and Medical Research Council (NHMRC). Several authors reported receiving grants or personal fees from or having ties with various sources, including NHMRC.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Do GLP-1s Lower VTE Risk in People With Type 2 Diabetes?
Overall, GLP-1 agonist use was associated with a 20% reduction in VTE, compared with DPP-4 inhibitor use, in those with type 2 diabetes, and this benefit held regardless of people’s obesity status, said study investigator Cho-Han Chiang, MD, a medical resident at Mount Auburn Hospital, Cambridge, Massachusetts, who presented the findings at the American Society of Hematology (ASH) 2024 Annual Meeting.
The incidence of VTE has increased by 20% over the past 10 years, and obesity is a risk factor for VTE, Chiang explained. A growing body of evidence demonstrated that GLP-1s provide a variety of cardiovascular benefits in people with type 2 diabetes, but data on VTE benefits remain more limited.
In the retrospective study, the researchers combed electronic health records from the TriNetX global database, which includes more than 250 million patients, and identified adults with type 2 diabetes who were taking a GLP-1 agonist or a DPP-4 inhibitor.
After excluding anyone with prior VTE or atrial fibrillation as well as those treated with both drugs or with oral anticoagulants, patients on GLP-1s were matched with those on DPP-4 inhibitors based on predetermined variables, including age, sex, race, body mass index (BMI), hemoglobin A1c, use of other antidiabetic agents, and underlying comorbidities. VTE was a composite of pulmonary embolism and deep vein thrombosis.
The researchers also performed a subgroup analysis that stratified patients by obesity status, defined as a BMI ≥ 30.
Within 1 year of GLP-1 or DPP-4 prescription, VTE occurred at a rate of 6.5 cases/1000 person-years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (hazard ratio [HR], 0.80; P < .001).
The 20% risk reduction in VTE held across various subgroups of BMI, including among those with obesity, Chiang reported.
Among patients with the highest BMI (≥ 40), VTE occurred at a rate of 7.2 cases/1000 person years in the GLP-1 group vs 9.6 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.74). Among patients with the next highest BMI (30-34.9), VTE occurred at a rate of 4.8 cases/1000 person years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.60). Among those with the lowest BMI (18.5-24.9), VTE occurred significantly less frequently among those in the GLP-1 group — 4.7 cases/1000 person years vs 7.4 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.61).
The lower risk for VTE associated with GLP-1s also held across the individual components of the composite VTE. Pulmonary embolism occurred at a rate of 3.1 cases/1000 person years in the GLP-1 group vs 3.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.78), and deep vein thrombosis occurred in 4.2 cases/1000 person years in the GLP-1 group vs 5.0 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.82).
Interestingly, the GLP-1 and DPP-4 curves started diverging within the first 30 days of the index prescription date, said Chiang.
Session moderator Ghadeer Dawwas, PhD, said in an interview that patients with type 2 diabetes are increasingly using GLP-1 agonists because of the cardiovascular benefits associated with the agents, which include lower risks for stroke and heart failure, but the antithrombotic benefits are still debated.
“The current study indicates that GLP-1 agonists may help lower the risk of VTE in patients with type 2 diabetes, irrespective of their baseline body weight,” said Dawwas, a pharmacoepidemiologist and assistant professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee. “However, given the current landscape of evidence and the existence of conflicting data on VTE risk, clinicians should proceed with caution and await further studies to validate these findings before making clinical decisions.”
This study was funded by the National Blood Clot Alliance and Conquer Cancer Foundation. Chiang and Dawwas had no disclosures.
A version of this article appeared on Medscape.com.
Overall, GLP-1 agonist use was associated with a 20% reduction in VTE, compared with DPP-4 inhibitor use, in those with type 2 diabetes, and this benefit held regardless of people’s obesity status, said study investigator Cho-Han Chiang, MD, a medical resident at Mount Auburn Hospital, Cambridge, Massachusetts, who presented the findings at the American Society of Hematology (ASH) 2024 Annual Meeting.
The incidence of VTE has increased by 20% over the past 10 years, and obesity is a risk factor for VTE, Chiang explained. A growing body of evidence demonstrated that GLP-1s provide a variety of cardiovascular benefits in people with type 2 diabetes, but data on VTE benefits remain more limited.
In the retrospective study, the researchers combed electronic health records from the TriNetX global database, which includes more than 250 million patients, and identified adults with type 2 diabetes who were taking a GLP-1 agonist or a DPP-4 inhibitor.
After excluding anyone with prior VTE or atrial fibrillation as well as those treated with both drugs or with oral anticoagulants, patients on GLP-1s were matched with those on DPP-4 inhibitors based on predetermined variables, including age, sex, race, body mass index (BMI), hemoglobin A1c, use of other antidiabetic agents, and underlying comorbidities. VTE was a composite of pulmonary embolism and deep vein thrombosis.
The researchers also performed a subgroup analysis that stratified patients by obesity status, defined as a BMI ≥ 30.
Within 1 year of GLP-1 or DPP-4 prescription, VTE occurred at a rate of 6.5 cases/1000 person-years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (hazard ratio [HR], 0.80; P < .001).
The 20% risk reduction in VTE held across various subgroups of BMI, including among those with obesity, Chiang reported.
Among patients with the highest BMI (≥ 40), VTE occurred at a rate of 7.2 cases/1000 person years in the GLP-1 group vs 9.6 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.74). Among patients with the next highest BMI (30-34.9), VTE occurred at a rate of 4.8 cases/1000 person years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.60). Among those with the lowest BMI (18.5-24.9), VTE occurred significantly less frequently among those in the GLP-1 group — 4.7 cases/1000 person years vs 7.4 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.61).
The lower risk for VTE associated with GLP-1s also held across the individual components of the composite VTE. Pulmonary embolism occurred at a rate of 3.1 cases/1000 person years in the GLP-1 group vs 3.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.78), and deep vein thrombosis occurred in 4.2 cases/1000 person years in the GLP-1 group vs 5.0 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.82).
Interestingly, the GLP-1 and DPP-4 curves started diverging within the first 30 days of the index prescription date, said Chiang.
Session moderator Ghadeer Dawwas, PhD, said in an interview that patients with type 2 diabetes are increasingly using GLP-1 agonists because of the cardiovascular benefits associated with the agents, which include lower risks for stroke and heart failure, but the antithrombotic benefits are still debated.
“The current study indicates that GLP-1 agonists may help lower the risk of VTE in patients with type 2 diabetes, irrespective of their baseline body weight,” said Dawwas, a pharmacoepidemiologist and assistant professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee. “However, given the current landscape of evidence and the existence of conflicting data on VTE risk, clinicians should proceed with caution and await further studies to validate these findings before making clinical decisions.”
This study was funded by the National Blood Clot Alliance and Conquer Cancer Foundation. Chiang and Dawwas had no disclosures.
A version of this article appeared on Medscape.com.
Overall, GLP-1 agonist use was associated with a 20% reduction in VTE, compared with DPP-4 inhibitor use, in those with type 2 diabetes, and this benefit held regardless of people’s obesity status, said study investigator Cho-Han Chiang, MD, a medical resident at Mount Auburn Hospital, Cambridge, Massachusetts, who presented the findings at the American Society of Hematology (ASH) 2024 Annual Meeting.
The incidence of VTE has increased by 20% over the past 10 years, and obesity is a risk factor for VTE, Chiang explained. A growing body of evidence demonstrated that GLP-1s provide a variety of cardiovascular benefits in people with type 2 diabetes, but data on VTE benefits remain more limited.
In the retrospective study, the researchers combed electronic health records from the TriNetX global database, which includes more than 250 million patients, and identified adults with type 2 diabetes who were taking a GLP-1 agonist or a DPP-4 inhibitor.
After excluding anyone with prior VTE or atrial fibrillation as well as those treated with both drugs or with oral anticoagulants, patients on GLP-1s were matched with those on DPP-4 inhibitors based on predetermined variables, including age, sex, race, body mass index (BMI), hemoglobin A1c, use of other antidiabetic agents, and underlying comorbidities. VTE was a composite of pulmonary embolism and deep vein thrombosis.
The researchers also performed a subgroup analysis that stratified patients by obesity status, defined as a BMI ≥ 30.
Within 1 year of GLP-1 or DPP-4 prescription, VTE occurred at a rate of 6.5 cases/1000 person-years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (hazard ratio [HR], 0.80; P < .001).
The 20% risk reduction in VTE held across various subgroups of BMI, including among those with obesity, Chiang reported.
Among patients with the highest BMI (≥ 40), VTE occurred at a rate of 7.2 cases/1000 person years in the GLP-1 group vs 9.6 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.74). Among patients with the next highest BMI (30-34.9), VTE occurred at a rate of 4.8 cases/1000 person years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.60). Among those with the lowest BMI (18.5-24.9), VTE occurred significantly less frequently among those in the GLP-1 group — 4.7 cases/1000 person years vs 7.4 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.61).
The lower risk for VTE associated with GLP-1s also held across the individual components of the composite VTE. Pulmonary embolism occurred at a rate of 3.1 cases/1000 person years in the GLP-1 group vs 3.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.78), and deep vein thrombosis occurred in 4.2 cases/1000 person years in the GLP-1 group vs 5.0 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.82).
Interestingly, the GLP-1 and DPP-4 curves started diverging within the first 30 days of the index prescription date, said Chiang.
Session moderator Ghadeer Dawwas, PhD, said in an interview that patients with type 2 diabetes are increasingly using GLP-1 agonists because of the cardiovascular benefits associated with the agents, which include lower risks for stroke and heart failure, but the antithrombotic benefits are still debated.
“The current study indicates that GLP-1 agonists may help lower the risk of VTE in patients with type 2 diabetes, irrespective of their baseline body weight,” said Dawwas, a pharmacoepidemiologist and assistant professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee. “However, given the current landscape of evidence and the existence of conflicting data on VTE risk, clinicians should proceed with caution and await further studies to validate these findings before making clinical decisions.”
This study was funded by the National Blood Clot Alliance and Conquer Cancer Foundation. Chiang and Dawwas had no disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024