Women's Health

Menopausal women with an intact uterus treated for a year with a daily, oral, single-pill formulation of estradiol and progesterone for the primary goal of reducing moderate to severe vasomotor symptoms showed evidence of reduced bone turnover in a post hoc, subgroup analysis of 157 women enrolled in the REPLENISH trial.

Ingram Publishing/Thinkstock

These findings “provide support for a potential skeletal benefit” when menopausal women with an intact uterus regularly used the tested estradiol plus progesterone formulation to treat moderate to severe vasomotor symptoms (VMS), Risa Kagan, MD, and associates wrote in an abstract released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting, and released abstracts for press coverage.

The reductions reported for three different markers of bone turnover compared with placebo control after 6 and 12 months on treatment with a U.S.-marketed estradiol plus progesterone formulation were ”reassuring and in line with expectations” said Lubna Pal, MBBS, professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., who was not involved with the study. But the findings fell short of addressing the more clinically relevant issue of whether the tested regimen reduces the rate of bone fractures.

The analysis included 56 women treated with 1.0 mg estradiol and 100 mg progesterone daily, 56 who received 0.5 mg estradiol and 100 mg progesterone daily, and 45 women in the placebo arm. It assessed changes from baseline in the on-treatment compared with placebo groups using immunoassays for bone-specific alkaline phosphatase (BSAP), C-terminal telopeptide of type 1 collagen (CTX-1), and N-terminal propeptide of type 1 procollagen (PINP). For this analysis, the researchers combined the two active-treatment arms, and found that all three markers showed statistically significant drops from baseline with treatment, compared with placebo at both 6- and 12-month follow-up. For all three markers, the declines on active treatment grew larger with time, and after 12 months the mean drops from baseline compared with placebo were an 18% relative reduction in BSAP, a 41% relative reduction in CTX-1, and a 29% relative reduction in PINP, reported Dr. Kagan, a gynecologist based in Berkeley, Calif., who is affiliated with the University of California San Francisco.

In addition to not yet providing more clinically meaningful results on bone fracture rates, Dr. Pal cited additional issues that limit interpretation of both these findings and the broader REPLENISH results. First, the new analysis of bone-turnover markers as reported in the abstract does not allow assessment of a possible dose-dependent effect on bone turnover. More importantly, while the full REPLENISH trial provided reassuring data on endometrial protection, it has not yet reported data on the other major safety concern of hormone replacement: the effects of treatment on breast cancer rates. “They need to show no harm” in breast tissue, Dr. Pal said in an interview. In addition, the positive effect reported on markers of bone turnover is not unique to this formulation. Other formulations with estrogen at similar dosages would have similar effects, she said.

Other considerations when using an oral formulation include the reduced risk for prothrombotic effects from estradiol when delivered transdermally instead of orally, although some women have trouble getting insurance coverage for transdermal formulations, Dr. Pal said. Oral estrogen is appropriate only for women without an elevated clotting risk. Daily progesterone treatment also is more problematic than a cyclical dosage regimen, but noncontinuous progesterone results in monthly bleeding, something that some women prefer to avoid. “I’m not convinced that continuous progesterone is a physiologic approach,” said Dr. Pal, a member of the Ob.Gyn. News editorial advisory board. In addition, some women may find the formulation attractive because both the estradiol and progesterone are bioidentical and not synthetic molecules.

In short, the oral estradiol plus progesterone formulation tested in REPLENISH “is another tool” that’s an option for selected menopausal women with a uterus. “The bone findings are in line with expectations and are reassuring. Long-term data are keenly awaited to understand whether the bone marker changes lead to fewer fractures. The impact of the treatment on breast safety will be especially important.” For women who want a bioidentical, oral option and to not have bleeding, the tested formulation can be an effective option providing both symptom benefit and endometrial protection, Dr. Pal said.

REPLENISH was funded by TherapeuticsMD, the company that markets the tested estradiol plus progesterone formulation (Bijuva). Dr. Kagan has been a consultant and adviser to and speaker on behalf of Therapeutics MD, and she has also been a consultant or adviser to or has spoken on behalf of AMAG, Amgen, Astellas, Lupin, Radius, and Warner Chilcott/Allergan, and she has received research funding from Endoceutics. Dr. Pal has been a consultant to Flow Health.

[email protected]

SOURCE: Kagan R et al. Obstet Gynecol. 2020 May;135:62S. doi: 10.1097/01.AOG.0000665076.20231.a8.

Menopausal women with an intact uterus treated for a year with a daily, oral, single-pill formulation of estradiol and progesterone for the primary goal of reducing moderate to severe vasomotor symptoms showed evidence of reduced bone turnover in a post hoc, subgroup analysis of 157 women enrolled in the REPLENISH trial.

Ingram Publishing/Thinkstock

These findings “provide support for a potential skeletal benefit” when menopausal women with an intact uterus regularly used the tested estradiol plus progesterone formulation to treat moderate to severe vasomotor symptoms (VMS), Risa Kagan, MD, and associates wrote in an abstract released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting, and released abstracts for press coverage.

The reductions reported for three different markers of bone turnover compared with placebo control after 6 and 12 months on treatment with a U.S.-marketed estradiol plus progesterone formulation were ”reassuring and in line with expectations” said Lubna Pal, MBBS, professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., who was not involved with the study. But the findings fell short of addressing the more clinically relevant issue of whether the tested regimen reduces the rate of bone fractures.

The analysis included 56 women treated with 1.0 mg estradiol and 100 mg progesterone daily, 56 who received 0.5 mg estradiol and 100 mg progesterone daily, and 45 women in the placebo arm. It assessed changes from baseline in the on-treatment compared with placebo groups using immunoassays for bone-specific alkaline phosphatase (BSAP), C-terminal telopeptide of type 1 collagen (CTX-1), and N-terminal propeptide of type 1 procollagen (PINP). For this analysis, the researchers combined the two active-treatment arms, and found that all three markers showed statistically significant drops from baseline with treatment, compared with placebo at both 6- and 12-month follow-up. For all three markers, the declines on active treatment grew larger with time, and after 12 months the mean drops from baseline compared with placebo were an 18% relative reduction in BSAP, a 41% relative reduction in CTX-1, and a 29% relative reduction in PINP, reported Dr. Kagan, a gynecologist based in Berkeley, Calif., who is affiliated with the University of California San Francisco.

In addition to not yet providing more clinically meaningful results on bone fracture rates, Dr. Pal cited additional issues that limit interpretation of both these findings and the broader REPLENISH results. First, the new analysis of bone-turnover markers as reported in the abstract does not allow assessment of a possible dose-dependent effect on bone turnover. More importantly, while the full REPLENISH trial provided reassuring data on endometrial protection, it has not yet reported data on the other major safety concern of hormone replacement: the effects of treatment on breast cancer rates. “They need to show no harm” in breast tissue, Dr. Pal said in an interview. In addition, the positive effect reported on markers of bone turnover is not unique to this formulation. Other formulations with estrogen at similar dosages would have similar effects, she said.

Other considerations when using an oral formulation include the reduced risk for prothrombotic effects from estradiol when delivered transdermally instead of orally, although some women have trouble getting insurance coverage for transdermal formulations, Dr. Pal said. Oral estrogen is appropriate only for women without an elevated clotting risk. Daily progesterone treatment also is more problematic than a cyclical dosage regimen, but noncontinuous progesterone results in monthly bleeding, something that some women prefer to avoid. “I’m not convinced that continuous progesterone is a physiologic approach,” said Dr. Pal, a member of the Ob.Gyn. News editorial advisory board. In addition, some women may find the formulation attractive because both the estradiol and progesterone are bioidentical and not synthetic molecules.

In short, the oral estradiol plus progesterone formulation tested in REPLENISH “is another tool” that’s an option for selected menopausal women with a uterus. “The bone findings are in line with expectations and are reassuring. Long-term data are keenly awaited to understand whether the bone marker changes lead to fewer fractures. The impact of the treatment on breast safety will be especially important.” For women who want a bioidentical, oral option and to not have bleeding, the tested formulation can be an effective option providing both symptom benefit and endometrial protection, Dr. Pal said.

REPLENISH was funded by TherapeuticsMD, the company that markets the tested estradiol plus progesterone formulation (Bijuva). Dr. Kagan has been a consultant and adviser to and speaker on behalf of Therapeutics MD, and she has also been a consultant or adviser to or has spoken on behalf of AMAG, Amgen, Astellas, Lupin, Radius, and Warner Chilcott/Allergan, and she has received research funding from Endoceutics. Dr. Pal has been a consultant to Flow Health.

[email protected]

SOURCE: Kagan R et al. Obstet Gynecol. 2020 May;135:62S. doi: 10.1097/01.AOG.0000665076.20231.a8.

Menopausal women with an intact uterus treated for a year with a daily, oral, single-pill formulation of estradiol and progesterone for the primary goal of reducing moderate to severe vasomotor symptoms showed evidence of reduced bone turnover in a post hoc, subgroup analysis of 157 women enrolled in the REPLENISH trial.

Ingram Publishing/Thinkstock

These findings “provide support for a potential skeletal benefit” when menopausal women with an intact uterus regularly used the tested estradiol plus progesterone formulation to treat moderate to severe vasomotor symptoms (VMS), Risa Kagan, MD, and associates wrote in an abstract released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting, and released abstracts for press coverage.

The reductions reported for three different markers of bone turnover compared with placebo control after 6 and 12 months on treatment with a U.S.-marketed estradiol plus progesterone formulation were ”reassuring and in line with expectations” said Lubna Pal, MBBS, professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., who was not involved with the study. But the findings fell short of addressing the more clinically relevant issue of whether the tested regimen reduces the rate of bone fractures.

The analysis included 56 women treated with 1.0 mg estradiol and 100 mg progesterone daily, 56 who received 0.5 mg estradiol and 100 mg progesterone daily, and 45 women in the placebo arm. It assessed changes from baseline in the on-treatment compared with placebo groups using immunoassays for bone-specific alkaline phosphatase (BSAP), C-terminal telopeptide of type 1 collagen (CTX-1), and N-terminal propeptide of type 1 procollagen (PINP). For this analysis, the researchers combined the two active-treatment arms, and found that all three markers showed statistically significant drops from baseline with treatment, compared with placebo at both 6- and 12-month follow-up. For all three markers, the declines on active treatment grew larger with time, and after 12 months the mean drops from baseline compared with placebo were an 18% relative reduction in BSAP, a 41% relative reduction in CTX-1, and a 29% relative reduction in PINP, reported Dr. Kagan, a gynecologist based in Berkeley, Calif., who is affiliated with the University of California San Francisco.

In addition to not yet providing more clinically meaningful results on bone fracture rates, Dr. Pal cited additional issues that limit interpretation of both these findings and the broader REPLENISH results. First, the new analysis of bone-turnover markers as reported in the abstract does not allow assessment of a possible dose-dependent effect on bone turnover. More importantly, while the full REPLENISH trial provided reassuring data on endometrial protection, it has not yet reported data on the other major safety concern of hormone replacement: the effects of treatment on breast cancer rates. “They need to show no harm” in breast tissue, Dr. Pal said in an interview. In addition, the positive effect reported on markers of bone turnover is not unique to this formulation. Other formulations with estrogen at similar dosages would have similar effects, she said.

Other considerations when using an oral formulation include the reduced risk for prothrombotic effects from estradiol when delivered transdermally instead of orally, although some women have trouble getting insurance coverage for transdermal formulations, Dr. Pal said. Oral estrogen is appropriate only for women without an elevated clotting risk. Daily progesterone treatment also is more problematic than a cyclical dosage regimen, but noncontinuous progesterone results in monthly bleeding, something that some women prefer to avoid. “I’m not convinced that continuous progesterone is a physiologic approach,” said Dr. Pal, a member of the Ob.Gyn. News editorial advisory board. In addition, some women may find the formulation attractive because both the estradiol and progesterone are bioidentical and not synthetic molecules.

In short, the oral estradiol plus progesterone formulation tested in REPLENISH “is another tool” that’s an option for selected menopausal women with a uterus. “The bone findings are in line with expectations and are reassuring. Long-term data are keenly awaited to understand whether the bone marker changes lead to fewer fractures. The impact of the treatment on breast safety will be especially important.” For women who want a bioidentical, oral option and to not have bleeding, the tested formulation can be an effective option providing both symptom benefit and endometrial protection, Dr. Pal said.

REPLENISH was funded by TherapeuticsMD, the company that markets the tested estradiol plus progesterone formulation (Bijuva). Dr. Kagan has been a consultant and adviser to and speaker on behalf of Therapeutics MD, and she has also been a consultant or adviser to or has spoken on behalf of AMAG, Amgen, Astellas, Lupin, Radius, and Warner Chilcott/Allergan, and she has received research funding from Endoceutics. Dr. Pal has been a consultant to Flow Health.

[email protected]

SOURCE: Kagan R et al. Obstet Gynecol. 2020 May;135:62S. doi: 10.1097/01.AOG.0000665076.20231.a8.

Like other agencies, the European Society for Medical Oncology has developed guidelines for managing breast cancer patients during the COVID-19 pandemic, recommending when care should be prioritized, delayed, or modified.

ESMO’s breast cancer guidelines expand upon guidelines issued by other groups, addressing a broad spectrum of patient profiles and providing a creative array of treatment options in COVID-19–era clinical practice.

As with ESMO’s other disease-focused COVID-19 guidelines, the breast cancer guidelines are organized by priority levels – high, medium, and low – which are applied to several domains of diagnosis and treatment.

High-priority recommendations apply to patients whose condition is either clinically unstable or whose cancer burden is immediately life-threatening.

Medium-priority recommendations apply to patients for whom delaying care beyond 6 weeks would probably lower the likelihood of a significant benefit from the intervention.

Low-priority recommendations apply to patients for whom services can be delayed for the duration of the COVID-19 pandemic.
 

Personalized care and high-priority situations

ESMO’s guidelines suggest that multidisciplinary tumor boards should guide decisions about the urgency of care for individual patients, given the complexity of breast cancer biology, the multiplicity of evidence-based treatments, and the possibility of cure or durable high-quality remissions.

The guidelines deliver a clear message that prepandemic discussions about delivering personalized care are even more important now.

ESMO prioritizes investigating high-risk screening mammography results (i.e., BIRADS 5), lumps noted on breast self-examination, clinical evidence of local-regional recurrence, and breast cancer in pregnant women.

Making these scenarios “high priority” will facilitate the best long-term outcomes in time-sensitive scenarios and improve patient satisfaction with care.

Modifications to consider

ESMO provides explicit options for treatment of common breast cancer profiles in which short-term modifications of standard management strategies can safely be considered. Given the generally long natural history of most breast cancer subtypes, these temporary modifications are unlikely to compromise long-term outcomes.

For patients with a new diagnosis of localized breast cancer, the guidelines recommend neoadjuvant chemotherapy, targeted therapy, or hormonal therapy to achieve optimal breast cancer outcomes and safely delay surgery or radiotherapy.

In the metastatic setting, ESMO advises providers to consider:

• Symptom-oriented testing, recognizing the arguable benefit of frequent imaging or serum tumor marker measurement (J Clin Oncol. 2016 Aug 20;34[24]:2820-6).
• Drug holidays, de-escalated maintenance therapy, and protracted schedules of bone-modifying agents.
• Avoiding mTOR and PI3KCA inhibitors as an addition to standard hormonal therapy because of pneumonitis, hyperglycemia, and immunosuppression risks. The guidelines suggest careful thought about adding CDK4/6 inhibitors to standard hormonal therapy because of the added burden of remote safety monitoring with the biologic agents.

ESMO makes suggestions about trimming the duration of adjuvant trastuzumab to 6 months, as in the PERSEPHONE study (Lancet. 2019 Jun 29;393[10191]:2599-612), and modifying the schedule of luteinizing hormone–releasing hormone agonist administration, in an effort to reduce patient exposure to health care personnel (and vice versa).

The guidelines recommend continuing clinical trials if benefits to patients outweigh risks and trials can be modified to enhance patient safety while preserving study endpoint evaluations.
 

Lower-priority situations

ESMO pointedly assigns a low priority to follow-up of patients who are at high risk of relapse but lack signs or symptoms of relapse.

Like other groups, ESMO recommends that patients with equivocal (i.e., BIRADS 3) screening mammograms should have 6-month follow-up imaging in preference to immediate core needle biopsy of the area(s) of concern.

ESMO uses age to assign priority for postponing adjuvant breast radiation in patients with low- to moderate-risk lesions. However, the guidelines stop surprisingly short of recommending that adjuvant radiation be withheld for older patients with low-risk, stage I, hormonally sensitive, HER2-negative breast cancers who receive endocrine therapy.
 

Bottom line

The pragmatic adjustments ESMO suggests address the challenges of evaluating and treating breast cancer patients during the COVID-19 pandemic. The guidelines protect each patient’s right to care and safety as well as protecting the safety of caregivers.

The guidelines will likely heighten patients’ satisfaction with care and decrease concern about adequacy of timely evaluation and treatment.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Like other agencies, the European Society for Medical Oncology has developed guidelines for managing breast cancer patients during the COVID-19 pandemic, recommending when care should be prioritized, delayed, or modified.

ESMO’s breast cancer guidelines expand upon guidelines issued by other groups, addressing a broad spectrum of patient profiles and providing a creative array of treatment options in COVID-19–era clinical practice.

As with ESMO’s other disease-focused COVID-19 guidelines, the breast cancer guidelines are organized by priority levels – high, medium, and low – which are applied to several domains of diagnosis and treatment.

High-priority recommendations apply to patients whose condition is either clinically unstable or whose cancer burden is immediately life-threatening.

Medium-priority recommendations apply to patients for whom delaying care beyond 6 weeks would probably lower the likelihood of a significant benefit from the intervention.

Low-priority recommendations apply to patients for whom services can be delayed for the duration of the COVID-19 pandemic.
 

Personalized care and high-priority situations

ESMO’s guidelines suggest that multidisciplinary tumor boards should guide decisions about the urgency of care for individual patients, given the complexity of breast cancer biology, the multiplicity of evidence-based treatments, and the possibility of cure or durable high-quality remissions.

The guidelines deliver a clear message that prepandemic discussions about delivering personalized care are even more important now.

ESMO prioritizes investigating high-risk screening mammography results (i.e., BIRADS 5), lumps noted on breast self-examination, clinical evidence of local-regional recurrence, and breast cancer in pregnant women.

Making these scenarios “high priority” will facilitate the best long-term outcomes in time-sensitive scenarios and improve patient satisfaction with care.

Modifications to consider

ESMO provides explicit options for treatment of common breast cancer profiles in which short-term modifications of standard management strategies can safely be considered. Given the generally long natural history of most breast cancer subtypes, these temporary modifications are unlikely to compromise long-term outcomes.

For patients with a new diagnosis of localized breast cancer, the guidelines recommend neoadjuvant chemotherapy, targeted therapy, or hormonal therapy to achieve optimal breast cancer outcomes and safely delay surgery or radiotherapy.

In the metastatic setting, ESMO advises providers to consider:

• Symptom-oriented testing, recognizing the arguable benefit of frequent imaging or serum tumor marker measurement (J Clin Oncol. 2016 Aug 20;34[24]:2820-6).
• Drug holidays, de-escalated maintenance therapy, and protracted schedules of bone-modifying agents.
• Avoiding mTOR and PI3KCA inhibitors as an addition to standard hormonal therapy because of pneumonitis, hyperglycemia, and immunosuppression risks. The guidelines suggest careful thought about adding CDK4/6 inhibitors to standard hormonal therapy because of the added burden of remote safety monitoring with the biologic agents.

ESMO makes suggestions about trimming the duration of adjuvant trastuzumab to 6 months, as in the PERSEPHONE study (Lancet. 2019 Jun 29;393[10191]:2599-612), and modifying the schedule of luteinizing hormone–releasing hormone agonist administration, in an effort to reduce patient exposure to health care personnel (and vice versa).

The guidelines recommend continuing clinical trials if benefits to patients outweigh risks and trials can be modified to enhance patient safety while preserving study endpoint evaluations.
 

Lower-priority situations

ESMO pointedly assigns a low priority to follow-up of patients who are at high risk of relapse but lack signs or symptoms of relapse.

Like other groups, ESMO recommends that patients with equivocal (i.e., BIRADS 3) screening mammograms should have 6-month follow-up imaging in preference to immediate core needle biopsy of the area(s) of concern.

ESMO uses age to assign priority for postponing adjuvant breast radiation in patients with low- to moderate-risk lesions. However, the guidelines stop surprisingly short of recommending that adjuvant radiation be withheld for older patients with low-risk, stage I, hormonally sensitive, HER2-negative breast cancers who receive endocrine therapy.
 

Bottom line

The pragmatic adjustments ESMO suggests address the challenges of evaluating and treating breast cancer patients during the COVID-19 pandemic. The guidelines protect each patient’s right to care and safety as well as protecting the safety of caregivers.

The guidelines will likely heighten patients’ satisfaction with care and decrease concern about adequacy of timely evaluation and treatment.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Like other agencies, the European Society for Medical Oncology has developed guidelines for managing breast cancer patients during the COVID-19 pandemic, recommending when care should be prioritized, delayed, or modified.

ESMO’s breast cancer guidelines expand upon guidelines issued by other groups, addressing a broad spectrum of patient profiles and providing a creative array of treatment options in COVID-19–era clinical practice.

As with ESMO’s other disease-focused COVID-19 guidelines, the breast cancer guidelines are organized by priority levels – high, medium, and low – which are applied to several domains of diagnosis and treatment.

High-priority recommendations apply to patients whose condition is either clinically unstable or whose cancer burden is immediately life-threatening.

Medium-priority recommendations apply to patients for whom delaying care beyond 6 weeks would probably lower the likelihood of a significant benefit from the intervention.

Low-priority recommendations apply to patients for whom services can be delayed for the duration of the COVID-19 pandemic.
 

Personalized care and high-priority situations

ESMO’s guidelines suggest that multidisciplinary tumor boards should guide decisions about the urgency of care for individual patients, given the complexity of breast cancer biology, the multiplicity of evidence-based treatments, and the possibility of cure or durable high-quality remissions.

The guidelines deliver a clear message that prepandemic discussions about delivering personalized care are even more important now.

ESMO prioritizes investigating high-risk screening mammography results (i.e., BIRADS 5), lumps noted on breast self-examination, clinical evidence of local-regional recurrence, and breast cancer in pregnant women.

Making these scenarios “high priority” will facilitate the best long-term outcomes in time-sensitive scenarios and improve patient satisfaction with care.

Modifications to consider

ESMO provides explicit options for treatment of common breast cancer profiles in which short-term modifications of standard management strategies can safely be considered. Given the generally long natural history of most breast cancer subtypes, these temporary modifications are unlikely to compromise long-term outcomes.

For patients with a new diagnosis of localized breast cancer, the guidelines recommend neoadjuvant chemotherapy, targeted therapy, or hormonal therapy to achieve optimal breast cancer outcomes and safely delay surgery or radiotherapy.

In the metastatic setting, ESMO advises providers to consider:

• Symptom-oriented testing, recognizing the arguable benefit of frequent imaging or serum tumor marker measurement (J Clin Oncol. 2016 Aug 20;34[24]:2820-6).
• Drug holidays, de-escalated maintenance therapy, and protracted schedules of bone-modifying agents.
• Avoiding mTOR and PI3KCA inhibitors as an addition to standard hormonal therapy because of pneumonitis, hyperglycemia, and immunosuppression risks. The guidelines suggest careful thought about adding CDK4/6 inhibitors to standard hormonal therapy because of the added burden of remote safety monitoring with the biologic agents.

ESMO makes suggestions about trimming the duration of adjuvant trastuzumab to 6 months, as in the PERSEPHONE study (Lancet. 2019 Jun 29;393[10191]:2599-612), and modifying the schedule of luteinizing hormone–releasing hormone agonist administration, in an effort to reduce patient exposure to health care personnel (and vice versa).

The guidelines recommend continuing clinical trials if benefits to patients outweigh risks and trials can be modified to enhance patient safety while preserving study endpoint evaluations.
 

Lower-priority situations

ESMO pointedly assigns a low priority to follow-up of patients who are at high risk of relapse but lack signs or symptoms of relapse.

Like other groups, ESMO recommends that patients with equivocal (i.e., BIRADS 3) screening mammograms should have 6-month follow-up imaging in preference to immediate core needle biopsy of the area(s) of concern.

ESMO uses age to assign priority for postponing adjuvant breast radiation in patients with low- to moderate-risk lesions. However, the guidelines stop surprisingly short of recommending that adjuvant radiation be withheld for older patients with low-risk, stage I, hormonally sensitive, HER2-negative breast cancers who receive endocrine therapy.
 

Bottom line

The pragmatic adjustments ESMO suggests address the challenges of evaluating and treating breast cancer patients during the COVID-19 pandemic. The guidelines protect each patient’s right to care and safety as well as protecting the safety of caregivers.

The guidelines will likely heighten patients’ satisfaction with care and decrease concern about adequacy of timely evaluation and treatment.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

We have all as providers experienced the tragic stillbirth of a term fetus for one of our patients. Too often no fetal movement was felt for days, but the patient never called. Or the patient did call, but the nonstress test (NST) was reactive or the ultrasound showed normal growth and fluid or the biophysical profile (BPP) was 8/8. Yet the patient still presented with a stillborn fetus a day later. Was the first patient simply so fearful of the likely deceased child within her that she did not call? Or did she simply not know to report it because she was not educated about what decreased fetal movement could mean? Could the second example have been prevented even though the testing was normal? I believe both scenarios could have been prevented with better education for both providers and patients.

The national stillbirth rate has remained relatively stagnant since 2000, despite many improvements in guidelines for the management of higher risk pregnancies.¹ We follow the growth of these pregnancies, do NSTs, and often induce these patients prior to the due date. We do this in the hope of having a healthy mom and baby. However, an analysis of 614 stillbirth cases and 1,816 control deliveries found that 81% of patients presenting with a stillborn baby had no risks factors that required additional monitoring.² Nearly 66% of 1,714 patients with a late stillbirth reported decreased fetal movement, no fetal movement, or a concerning increase in fetal movement in the days leading up to their baby’s death.³ Studies have suggested that persistent decreased fetal movement has an odds ratio for stillbirth of 4.51,⁴ which is higher than hypertensive disease and diabetes for this same outcome by nearly a factor of two. Yet there are no formal guidelines on education for patients or management of this chief complaint.

We assess fetal movement at every prenatal visit but patients who experienced stillbirth will say they didn’t know why. This is because as a culture and a profession we are afraid to talk about such a taboo subject as stillbirth. We are afraid we will scare our patients if we tell them that a decrease in fetal movement or no fetal movement may be because their baby is at risk for this dreaded complication. On one level this argument makes sense, but as soon as the baby is born we give parents plenty of education and advice to keep their children safe. Telling a parent to remove all bedding, put their baby on their back, and keep their baby from being too warm to prevent sudden infant death syndrome (SIDS) is very scary. However, this education is necessary. If moms simply know the reason why we ask about fetal movements, they may not wait 2 days before they call. We must have faith that pregnant women can handle this education about decreased fetal movement.

Next most important is our response to the complaint of decreased fetal movement. Often when the NST is reactive or the ultrasound is normal, we assume the baby is at no risk and we reassure the mother that everything is fine. We often tell moms the false myth that babies slow down at the end or advise kick counts after this complaint despite studies failing to show their utility. Because the education about kick count is frequency is what matters, a mother may not call if there is a change in pattern or strength – even if she is very worried about this. A baby may “pass” a kick count, but a mom still may be very worried, yet she will not call because the baby “passed.”

Protocols from the United Kingdom and Australia focus on the assumption that the complaint of decreased fetal movement may be the only warning sign of impending stillbirth. Harvey Kliman, MD, PhD, director of reproductive and placental research unit at Yale University, New Haven, Conn. said an analogy to this is a car driving 55 miles per hour despite only 10 miles of gas being left in the tank.* The car is running fine even when it is almost out of gas. That may be why we all have seen a fetus with recent reassuring tests in the last few days who presents stillborn. Perhaps the only warning sign is decreased fetal movement – not a nonreactive NST or low score BPP. Placental insufficiency is often the cause of initially unexplained stillbirth, far more common than “cord accidents.” If we liken the placenta to the “gas tank” for the pregnancy, then decreased fetal movement may be the “low gas” signal on the dashboard. After this patient has a reactive NST and/or reassuring ultrasound, we need to ask her if she is reassured. Data from a study of 380 women found that women who had a gut instinct that something was wrong were 23 times more likely to experience a stillbirth, according to the unadjusted odds ratio from the logistic regression model.⁵ We should follow up closely with moms who are not reassured and consider induction if they are over 39 weeks. We should tell every mom who presents with a concern about fetal movement that she did the right thing, and we want to hear from her again immediately if the movement is decreased again or persists. We cannot make women feel silly for calling. We should do an ultrasound for worried moms even if the NST is reactive to make sure we are not missing oligohydramnios or fetal growth restriction; the latter is the biggest known risk factor for stillbirth. We also should perform an ultrasound for moms with risk factors for stillbirth such as advanced maternal age or black race.

Dr. Florescue is an ob.gyn. in private practice at Women Gynecology and Childbirth Associates in Rochester, N.Y. She delivers babies at Highland Hospital in Rochester. She has no relevant financial disclosures.
 

References

1. The Lancet. 2016, Jan 18;387(10018):587-603.

2. JAMA. 2011 Dec 14;306(22):2469-79.

3. BMC Pregnancy Childbirth. 2015 Aug 15;15:172.

4. BMJ Open. 2018 Jul 6;8(7):e020031.

5. Midwifery. 2018 Jul;62:171-6.

6. The Lancet. 2016, Jan 18;387(10019):691-702.

*This article was updated on 5/4/2020.

We have all as providers experienced the tragic stillbirth of a term fetus for one of our patients. Too often no fetal movement was felt for days, but the patient never called. Or the patient did call, but the nonstress test (NST) was reactive or the ultrasound showed normal growth and fluid or the biophysical profile (BPP) was 8/8. Yet the patient still presented with a stillborn fetus a day later. Was the first patient simply so fearful of the likely deceased child within her that she did not call? Or did she simply not know to report it because she was not educated about what decreased fetal movement could mean? Could the second example have been prevented even though the testing was normal? I believe both scenarios could have been prevented with better education for both providers and patients.

The national stillbirth rate has remained relatively stagnant since 2000, despite many improvements in guidelines for the management of higher risk pregnancies.¹ We follow the growth of these pregnancies, do NSTs, and often induce these patients prior to the due date. We do this in the hope of having a healthy mom and baby. However, an analysis of 614 stillbirth cases and 1,816 control deliveries found that 81% of patients presenting with a stillborn baby had no risks factors that required additional monitoring.² Nearly 66% of 1,714 patients with a late stillbirth reported decreased fetal movement, no fetal movement, or a concerning increase in fetal movement in the days leading up to their baby’s death.³ Studies have suggested that persistent decreased fetal movement has an odds ratio for stillbirth of 4.51,⁴ which is higher than hypertensive disease and diabetes for this same outcome by nearly a factor of two. Yet there are no formal guidelines on education for patients or management of this chief complaint.

We assess fetal movement at every prenatal visit but patients who experienced stillbirth will say they didn’t know why. This is because as a culture and a profession we are afraid to talk about such a taboo subject as stillbirth. We are afraid we will scare our patients if we tell them that a decrease in fetal movement or no fetal movement may be because their baby is at risk for this dreaded complication. On one level this argument makes sense, but as soon as the baby is born we give parents plenty of education and advice to keep their children safe. Telling a parent to remove all bedding, put their baby on their back, and keep their baby from being too warm to prevent sudden infant death syndrome (SIDS) is very scary. However, this education is necessary. If moms simply know the reason why we ask about fetal movements, they may not wait 2 days before they call. We must have faith that pregnant women can handle this education about decreased fetal movement.

Next most important is our response to the complaint of decreased fetal movement. Often when the NST is reactive or the ultrasound is normal, we assume the baby is at no risk and we reassure the mother that everything is fine. We often tell moms the false myth that babies slow down at the end or advise kick counts after this complaint despite studies failing to show their utility. Because the education about kick count is frequency is what matters, a mother may not call if there is a change in pattern or strength – even if she is very worried about this. A baby may “pass” a kick count, but a mom still may be very worried, yet she will not call because the baby “passed.”

Protocols from the United Kingdom and Australia focus on the assumption that the complaint of decreased fetal movement may be the only warning sign of impending stillbirth. Harvey Kliman, MD, PhD, director of reproductive and placental research unit at Yale University, New Haven, Conn. said an analogy to this is a car driving 55 miles per hour despite only 10 miles of gas being left in the tank.* The car is running fine even when it is almost out of gas. That may be why we all have seen a fetus with recent reassuring tests in the last few days who presents stillborn. Perhaps the only warning sign is decreased fetal movement – not a nonreactive NST or low score BPP. Placental insufficiency is often the cause of initially unexplained stillbirth, far more common than “cord accidents.” If we liken the placenta to the “gas tank” for the pregnancy, then decreased fetal movement may be the “low gas” signal on the dashboard. After this patient has a reactive NST and/or reassuring ultrasound, we need to ask her if she is reassured. Data from a study of 380 women found that women who had a gut instinct that something was wrong were 23 times more likely to experience a stillbirth, according to the unadjusted odds ratio from the logistic regression model.⁵ We should follow up closely with moms who are not reassured and consider induction if they are over 39 weeks. We should tell every mom who presents with a concern about fetal movement that she did the right thing, and we want to hear from her again immediately if the movement is decreased again or persists. We cannot make women feel silly for calling. We should do an ultrasound for worried moms even if the NST is reactive to make sure we are not missing oligohydramnios or fetal growth restriction; the latter is the biggest known risk factor for stillbirth. We also should perform an ultrasound for moms with risk factors for stillbirth such as advanced maternal age or black race.

Dr. Florescue is an ob.gyn. in private practice at Women Gynecology and Childbirth Associates in Rochester, N.Y. She delivers babies at Highland Hospital in Rochester. She has no relevant financial disclosures.
 

References

1. The Lancet. 2016, Jan 18;387(10018):587-603.

2. JAMA. 2011 Dec 14;306(22):2469-79.

3. BMC Pregnancy Childbirth. 2015 Aug 15;15:172.

4. BMJ Open. 2018 Jul 6;8(7):e020031.

5. Midwifery. 2018 Jul;62:171-6.

6. The Lancet. 2016, Jan 18;387(10019):691-702.

*This article was updated on 5/4/2020.

We have all as providers experienced the tragic stillbirth of a term fetus for one of our patients. Too often no fetal movement was felt for days, but the patient never called. Or the patient did call, but the nonstress test (NST) was reactive or the ultrasound showed normal growth and fluid or the biophysical profile (BPP) was 8/8. Yet the patient still presented with a stillborn fetus a day later. Was the first patient simply so fearful of the likely deceased child within her that she did not call? Or did she simply not know to report it because she was not educated about what decreased fetal movement could mean? Could the second example have been prevented even though the testing was normal? I believe both scenarios could have been prevented with better education for both providers and patients.

The national stillbirth rate has remained relatively stagnant since 2000, despite many improvements in guidelines for the management of higher risk pregnancies.¹ We follow the growth of these pregnancies, do NSTs, and often induce these patients prior to the due date. We do this in the hope of having a healthy mom and baby. However, an analysis of 614 stillbirth cases and 1,816 control deliveries found that 81% of patients presenting with a stillborn baby had no risks factors that required additional monitoring.² Nearly 66% of 1,714 patients with a late stillbirth reported decreased fetal movement, no fetal movement, or a concerning increase in fetal movement in the days leading up to their baby’s death.³ Studies have suggested that persistent decreased fetal movement has an odds ratio for stillbirth of 4.51,⁴ which is higher than hypertensive disease and diabetes for this same outcome by nearly a factor of two. Yet there are no formal guidelines on education for patients or management of this chief complaint.

We assess fetal movement at every prenatal visit but patients who experienced stillbirth will say they didn’t know why. This is because as a culture and a profession we are afraid to talk about such a taboo subject as stillbirth. We are afraid we will scare our patients if we tell them that a decrease in fetal movement or no fetal movement may be because their baby is at risk for this dreaded complication. On one level this argument makes sense, but as soon as the baby is born we give parents plenty of education and advice to keep their children safe. Telling a parent to remove all bedding, put their baby on their back, and keep their baby from being too warm to prevent sudden infant death syndrome (SIDS) is very scary. However, this education is necessary. If moms simply know the reason why we ask about fetal movements, they may not wait 2 days before they call. We must have faith that pregnant women can handle this education about decreased fetal movement.

Next most important is our response to the complaint of decreased fetal movement. Often when the NST is reactive or the ultrasound is normal, we assume the baby is at no risk and we reassure the mother that everything is fine. We often tell moms the false myth that babies slow down at the end or advise kick counts after this complaint despite studies failing to show their utility. Because the education about kick count is frequency is what matters, a mother may not call if there is a change in pattern or strength – even if she is very worried about this. A baby may “pass” a kick count, but a mom still may be very worried, yet she will not call because the baby “passed.”

Protocols from the United Kingdom and Australia focus on the assumption that the complaint of decreased fetal movement may be the only warning sign of impending stillbirth. Harvey Kliman, MD, PhD, director of reproductive and placental research unit at Yale University, New Haven, Conn. said an analogy to this is a car driving 55 miles per hour despite only 10 miles of gas being left in the tank.* The car is running fine even when it is almost out of gas. That may be why we all have seen a fetus with recent reassuring tests in the last few days who presents stillborn. Perhaps the only warning sign is decreased fetal movement – not a nonreactive NST or low score BPP. Placental insufficiency is often the cause of initially unexplained stillbirth, far more common than “cord accidents.” If we liken the placenta to the “gas tank” for the pregnancy, then decreased fetal movement may be the “low gas” signal on the dashboard. After this patient has a reactive NST and/or reassuring ultrasound, we need to ask her if she is reassured. Data from a study of 380 women found that women who had a gut instinct that something was wrong were 23 times more likely to experience a stillbirth, according to the unadjusted odds ratio from the logistic regression model.⁵ We should follow up closely with moms who are not reassured and consider induction if they are over 39 weeks. We should tell every mom who presents with a concern about fetal movement that she did the right thing, and we want to hear from her again immediately if the movement is decreased again or persists. We cannot make women feel silly for calling. We should do an ultrasound for worried moms even if the NST is reactive to make sure we are not missing oligohydramnios or fetal growth restriction; the latter is the biggest known risk factor for stillbirth. We also should perform an ultrasound for moms with risk factors for stillbirth such as advanced maternal age or black race.

Dr. Florescue is an ob.gyn. in private practice at Women Gynecology and Childbirth Associates in Rochester, N.Y. She delivers babies at Highland Hospital in Rochester. She has no relevant financial disclosures.
 

References

1. The Lancet. 2016, Jan 18;387(10018):587-603.

2. JAMA. 2011 Dec 14;306(22):2469-79.

3. BMC Pregnancy Childbirth. 2015 Aug 15;15:172.

4. BMJ Open. 2018 Jul 6;8(7):e020031.

5. Midwifery. 2018 Jul;62:171-6.

6. The Lancet. 2016, Jan 18;387(10019):691-702.

*This article was updated on 5/4/2020.

Application of enhanced recovery after surgery (ERAS) protocols significantly reduced the use of opioids, as well as hospital stays and hospital costs, based on data from cohorts of women before and after the introduction of the protocols.

selimaksan/E+

The findings were released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.

ERAS protocols have been introduced in surgical specialties including colorectal, urologic, gynecologic, and hepatobiliary – with noted benefits to patients and the health care system, wrote Nnamdi I. Gwacham, DO, of Saint Barnabas Medical Center, Livingston, N.J., and colleagues.

The researchers explored the impact of ERAS on reduction in opioid use after cesarean sections at a community teaching hospital in a retrospective study also published in Obstetrics & Gynecology.

The study population included a historical cohort of 2,109 patients from 2018 before the establishment of the ERAS pathway and 1,463 patients since the ERAS pathway was established in 2019.*

Significantly fewer patients in the ERAS group required opioids, compared with the historical group (1,766 vs. 341). A total of 8,082 opioid units were used before the introduction of the ERAS pathway, compared with 803 units used since its introduction, Dr. Gwacham and associates reported. The study was a Donald F. Richardson Prize Paper.

The ERAS pathway consisted of received transversus abdominis plane blocks in the immediate postoperative period (given to 98% of the patients), and all patients were started on “a scheduled multimodal analgesia with a combination of ibuprofen, acetaminophen, and dextromethorphan until discharge,” the researchers wrote. Patients received opioids only if their pain was not well controlled with the ERAS protocol.

In addition, patients who received ERAS had significantly shorter hospital stays than the historical group (3.19 days vs. 2.63 days) and incurred a significantly lower average direct cost ($4,290 vs. $3,957).

The groups were not significantly different in age, race, or body mass index.

“Given the current opioid epidemic in America, researching ways to reduce their use is an urgent matter,” Angela Martin, MD, of the University of Kansas, Kansas City, said in an interview.

She thought the study findings were to be expected based on research in other areas. “Given the trends and ability to reduced opioid use with ERAS in other specialties, it does not surprise me that women recovering from cesarean sections are similar.”

The take-home message for clinicians: “Begin thinking outside of the box when it comes to pain control,” emphasized Dr. Martin, who was not a part of this study. “Opioids don’t have to be the first line medications for postoperative pain management.”

She added that additional directions for research could include the patient perspective on postoperative pain management after a cesarean delivery. “Alternative options to opioids would be even more enticing if the inpatient experience was also improved,” said Dr. Martin, who is a member of the Ob.Gyn News editorial advisory board.

The researchers had no financial conflicts to disclose. Dr. Martin had no relevant financial disclosures.

SOURCE: Gwacham NI et al. Obstet Gynecol. 2020 May;135:2S. doi: 10.1097/01.AOG.0000662880.08512.6b.

*This article was updated on 4/29/2020.

Application of enhanced recovery after surgery (ERAS) protocols significantly reduced the use of opioids, as well as hospital stays and hospital costs, based on data from cohorts of women before and after the introduction of the protocols.

selimaksan/E+

The findings were released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.

ERAS protocols have been introduced in surgical specialties including colorectal, urologic, gynecologic, and hepatobiliary – with noted benefits to patients and the health care system, wrote Nnamdi I. Gwacham, DO, of Saint Barnabas Medical Center, Livingston, N.J., and colleagues.

The researchers explored the impact of ERAS on reduction in opioid use after cesarean sections at a community teaching hospital in a retrospective study also published in Obstetrics & Gynecology.

The study population included a historical cohort of 2,109 patients from 2018 before the establishment of the ERAS pathway and 1,463 patients since the ERAS pathway was established in 2019.*

Significantly fewer patients in the ERAS group required opioids, compared with the historical group (1,766 vs. 341). A total of 8,082 opioid units were used before the introduction of the ERAS pathway, compared with 803 units used since its introduction, Dr. Gwacham and associates reported. The study was a Donald F. Richardson Prize Paper.

The ERAS pathway consisted of received transversus abdominis plane blocks in the immediate postoperative period (given to 98% of the patients), and all patients were started on “a scheduled multimodal analgesia with a combination of ibuprofen, acetaminophen, and dextromethorphan until discharge,” the researchers wrote. Patients received opioids only if their pain was not well controlled with the ERAS protocol.

In addition, patients who received ERAS had significantly shorter hospital stays than the historical group (3.19 days vs. 2.63 days) and incurred a significantly lower average direct cost ($4,290 vs. $3,957).

The groups were not significantly different in age, race, or body mass index.

“Given the current opioid epidemic in America, researching ways to reduce their use is an urgent matter,” Angela Martin, MD, of the University of Kansas, Kansas City, said in an interview.

She thought the study findings were to be expected based on research in other areas. “Given the trends and ability to reduced opioid use with ERAS in other specialties, it does not surprise me that women recovering from cesarean sections are similar.”

The take-home message for clinicians: “Begin thinking outside of the box when it comes to pain control,” emphasized Dr. Martin, who was not a part of this study. “Opioids don’t have to be the first line medications for postoperative pain management.”

She added that additional directions for research could include the patient perspective on postoperative pain management after a cesarean delivery. “Alternative options to opioids would be even more enticing if the inpatient experience was also improved,” said Dr. Martin, who is a member of the Ob.Gyn News editorial advisory board.

The researchers had no financial conflicts to disclose. Dr. Martin had no relevant financial disclosures.

SOURCE: Gwacham NI et al. Obstet Gynecol. 2020 May;135:2S. doi: 10.1097/01.AOG.0000662880.08512.6b.

*This article was updated on 4/29/2020.

Application of enhanced recovery after surgery (ERAS) protocols significantly reduced the use of opioids, as well as hospital stays and hospital costs, based on data from cohorts of women before and after the introduction of the protocols.

selimaksan/E+

The findings were released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.

ERAS protocols have been introduced in surgical specialties including colorectal, urologic, gynecologic, and hepatobiliary – with noted benefits to patients and the health care system, wrote Nnamdi I. Gwacham, DO, of Saint Barnabas Medical Center, Livingston, N.J., and colleagues.

The researchers explored the impact of ERAS on reduction in opioid use after cesarean sections at a community teaching hospital in a retrospective study also published in Obstetrics & Gynecology.

The study population included a historical cohort of 2,109 patients from 2018 before the establishment of the ERAS pathway and 1,463 patients since the ERAS pathway was established in 2019.*

Significantly fewer patients in the ERAS group required opioids, compared with the historical group (1,766 vs. 341). A total of 8,082 opioid units were used before the introduction of the ERAS pathway, compared with 803 units used since its introduction, Dr. Gwacham and associates reported. The study was a Donald F. Richardson Prize Paper.

The ERAS pathway consisted of received transversus abdominis plane blocks in the immediate postoperative period (given to 98% of the patients), and all patients were started on “a scheduled multimodal analgesia with a combination of ibuprofen, acetaminophen, and dextromethorphan until discharge,” the researchers wrote. Patients received opioids only if their pain was not well controlled with the ERAS protocol.

In addition, patients who received ERAS had significantly shorter hospital stays than the historical group (3.19 days vs. 2.63 days) and incurred a significantly lower average direct cost ($4,290 vs. $3,957).

The groups were not significantly different in age, race, or body mass index.

“Given the current opioid epidemic in America, researching ways to reduce their use is an urgent matter,” Angela Martin, MD, of the University of Kansas, Kansas City, said in an interview.

She thought the study findings were to be expected based on research in other areas. “Given the trends and ability to reduced opioid use with ERAS in other specialties, it does not surprise me that women recovering from cesarean sections are similar.”

The take-home message for clinicians: “Begin thinking outside of the box when it comes to pain control,” emphasized Dr. Martin, who was not a part of this study. “Opioids don’t have to be the first line medications for postoperative pain management.”

She added that additional directions for research could include the patient perspective on postoperative pain management after a cesarean delivery. “Alternative options to opioids would be even more enticing if the inpatient experience was also improved,” said Dr. Martin, who is a member of the Ob.Gyn News editorial advisory board.

The researchers had no financial conflicts to disclose. Dr. Martin had no relevant financial disclosures.

SOURCE: Gwacham NI et al. Obstet Gynecol. 2020 May;135:2S. doi: 10.1097/01.AOG.0000662880.08512.6b.

*This article was updated on 4/29/2020.

Vaginal cleansing before cesarean delivery was successfully implemented – and significantly decreased the rate of surgical site infections (SSI) – in a quality improvement study done at Thomas Jefferson University Hospital in Philadelphia.

“Our goal was not to prove that vaginal preparation [before cesarean section] works, because that’s already been shown in large randomized, controlled trials, but to show that we can implement it and that we can see the same results in real life,” lead investigator Johanna Quist-Nelson, MD, said in an interview.

Dr. Quist-Nelson, a third-year fellow at the hospital and the department of obstetrics and gynecology at Sidney Kimmel Medical College, Philadelphia, was scheduled to present the findings at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.

Resident and staff physicians as well as nursing and operating room staff were educated/reminded through a multipronged intervention about the benefits of vaginal cleansing with a sponge stick preparation of 10% povidone-iodine solution (Betadine) – and later about the potential benefits of intravenous azithromycin – immediately before cesarean delivery for women in labor and women with ruptured membranes.

Dr. Quist-Nelson and coinvestigators compared three periods of time: 12 months preintervention, 14 months with vaginal cleansing promoted for infection prophylaxis, and 16 months of instructions for both vaginal cleansing and intravenous azithromycin. The three periods captured 1,033 patients. The researchers used control charts – a tool “often used in implementation science,” she said – to analyze monthly data and assess trends for SSI rates and for compliance.

The rate of SSI – as defined by the Centers for Disease Control and Prevention – decreased by 33%, they found, from 23% to 15%. The drop occurred mainly 4 months into the vaginal cleansing portion of the study and was sustained during the following 26 months. The addition of intravenous azithromycin education did not result in any further change in the SSI rate, Dr. Quist-Nelson and associates reported in the study – the abstract for which was published in Obstetrics & Gynecology. It won a third-place prize among the papers on current clinical and basic investigation.

Compliance with the vaginal cleansing protocol increased from 60% at the start of the vaginal cleansing phase to 85% 1 year later. Azithromycin compliance rose to 75% over the third phase of the intervention.

Vaginal cleansing has received attention at Thomas Jefferson for several years. In 2017, researchers there collaborated with investigators in Italy on a systemic review and meta-analysis which concluded that women who received vaginal cleansing before cesarean delivery – most commonly with 10% povidine-iodine – had a significantly lower incidence of endometritis (Obstet Gynecol. 2017 Sep;130[3]:527-38).

A subgroup analysis showed that the benefit of vaginal cleansing was limited to “those women who have a cesarean section after their water breaks or when they’re in labor,” Dr. Quist-Nelson said.

Azithromycin similarly was found to reduce the risk of postoperative infection in women undergoing nonelective cesarean deliveries in a randomized trial published in 2016 (N Engl J Med. 2016 Sep 29;375[13]:1231-41). While the new quality improvement study did not suggest any additional benefit to intravenous azithromycin, “we continue to offer it [at our hospital] because it has been shown [in prior research] to be beneficial and because our study wasn’t [designed] to show benefit,” Dr. Quist-Nelson said.

The quality improvement intervention included hands-on training on vaginal cleansing for resident physicians and e-mail reminders for physician staff, and daily reviews for 1 week on intravenous azithromycin for resident physicians and EMR “best practice advisory” reminders for physician staff. “We also wrote a protocol available online, and put reminders in our OR notes, as well as trained the nursing staff and OR staff,” she said.

Catherine Cansino, MD, MPH, of the University of California, Davis, said in an interview that SSI rates are “problematic [in obstetrics], not only because of morbidity but also potential cost because of rehospitalization.” The study shows that vaginal cleansing “is absolutely a good target for quality improvement,” she said. “It’s promising, and very exciting to see something like this have such a dramatic positive result.” Dr. Cansino, who is a member of the Ob.Gyn News editorial advisory board, was not involved in this study.

Thomas Jefferson Hospital has had relatively high SSI rates, Dr. Quist-Nelson noted.

Dr. Quist-Nelson and coinvestigators did not report any potential conflicts of interest. Dr. Cansino also did not report any potential conflicts of interest.
 

SOURCE: Quist-Nelson J et al. Obstet. Gynecol. 2020 May;135:1S. doi: 10.1097/01.AOG.0000662876.23603.13.

Vaginal cleansing before cesarean delivery was successfully implemented – and significantly decreased the rate of surgical site infections (SSI) – in a quality improvement study done at Thomas Jefferson University Hospital in Philadelphia.

“Our goal was not to prove that vaginal preparation [before cesarean section] works, because that’s already been shown in large randomized, controlled trials, but to show that we can implement it and that we can see the same results in real life,” lead investigator Johanna Quist-Nelson, MD, said in an interview.

Dr. Quist-Nelson, a third-year fellow at the hospital and the department of obstetrics and gynecology at Sidney Kimmel Medical College, Philadelphia, was scheduled to present the findings at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.

Resident and staff physicians as well as nursing and operating room staff were educated/reminded through a multipronged intervention about the benefits of vaginal cleansing with a sponge stick preparation of 10% povidone-iodine solution (Betadine) – and later about the potential benefits of intravenous azithromycin – immediately before cesarean delivery for women in labor and women with ruptured membranes.

Dr. Quist-Nelson and coinvestigators compared three periods of time: 12 months preintervention, 14 months with vaginal cleansing promoted for infection prophylaxis, and 16 months of instructions for both vaginal cleansing and intravenous azithromycin. The three periods captured 1,033 patients. The researchers used control charts – a tool “often used in implementation science,” she said – to analyze monthly data and assess trends for SSI rates and for compliance.

The rate of SSI – as defined by the Centers for Disease Control and Prevention – decreased by 33%, they found, from 23% to 15%. The drop occurred mainly 4 months into the vaginal cleansing portion of the study and was sustained during the following 26 months. The addition of intravenous azithromycin education did not result in any further change in the SSI rate, Dr. Quist-Nelson and associates reported in the study – the abstract for which was published in Obstetrics & Gynecology. It won a third-place prize among the papers on current clinical and basic investigation.

Compliance with the vaginal cleansing protocol increased from 60% at the start of the vaginal cleansing phase to 85% 1 year later. Azithromycin compliance rose to 75% over the third phase of the intervention.

Vaginal cleansing has received attention at Thomas Jefferson for several years. In 2017, researchers there collaborated with investigators in Italy on a systemic review and meta-analysis which concluded that women who received vaginal cleansing before cesarean delivery – most commonly with 10% povidine-iodine – had a significantly lower incidence of endometritis (Obstet Gynecol. 2017 Sep;130[3]:527-38).

A subgroup analysis showed that the benefit of vaginal cleansing was limited to “those women who have a cesarean section after their water breaks or when they’re in labor,” Dr. Quist-Nelson said.

Azithromycin similarly was found to reduce the risk of postoperative infection in women undergoing nonelective cesarean deliveries in a randomized trial published in 2016 (N Engl J Med. 2016 Sep 29;375[13]:1231-41). While the new quality improvement study did not suggest any additional benefit to intravenous azithromycin, “we continue to offer it [at our hospital] because it has been shown [in prior research] to be beneficial and because our study wasn’t [designed] to show benefit,” Dr. Quist-Nelson said.

The quality improvement intervention included hands-on training on vaginal cleansing for resident physicians and e-mail reminders for physician staff, and daily reviews for 1 week on intravenous azithromycin for resident physicians and EMR “best practice advisory” reminders for physician staff. “We also wrote a protocol available online, and put reminders in our OR notes, as well as trained the nursing staff and OR staff,” she said.

Catherine Cansino, MD, MPH, of the University of California, Davis, said in an interview that SSI rates are “problematic [in obstetrics], not only because of morbidity but also potential cost because of rehospitalization.” The study shows that vaginal cleansing “is absolutely a good target for quality improvement,” she said. “It’s promising, and very exciting to see something like this have such a dramatic positive result.” Dr. Cansino, who is a member of the Ob.Gyn News editorial advisory board, was not involved in this study.

Thomas Jefferson Hospital has had relatively high SSI rates, Dr. Quist-Nelson noted.

Dr. Quist-Nelson and coinvestigators did not report any potential conflicts of interest. Dr. Cansino also did not report any potential conflicts of interest.
 

SOURCE: Quist-Nelson J et al. Obstet. Gynecol. 2020 May;135:1S. doi: 10.1097/01.AOG.0000662876.23603.13.

Vaginal cleansing before cesarean delivery was successfully implemented – and significantly decreased the rate of surgical site infections (SSI) – in a quality improvement study done at Thomas Jefferson University Hospital in Philadelphia.

“Our goal was not to prove that vaginal preparation [before cesarean section] works, because that’s already been shown in large randomized, controlled trials, but to show that we can implement it and that we can see the same results in real life,” lead investigator Johanna Quist-Nelson, MD, said in an interview.

Dr. Quist-Nelson, a third-year fellow at the hospital and the department of obstetrics and gynecology at Sidney Kimmel Medical College, Philadelphia, was scheduled to present the findings at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.

Resident and staff physicians as well as nursing and operating room staff were educated/reminded through a multipronged intervention about the benefits of vaginal cleansing with a sponge stick preparation of 10% povidone-iodine solution (Betadine) – and later about the potential benefits of intravenous azithromycin – immediately before cesarean delivery for women in labor and women with ruptured membranes.

Dr. Quist-Nelson and coinvestigators compared three periods of time: 12 months preintervention, 14 months with vaginal cleansing promoted for infection prophylaxis, and 16 months of instructions for both vaginal cleansing and intravenous azithromycin. The three periods captured 1,033 patients. The researchers used control charts – a tool “often used in implementation science,” she said – to analyze monthly data and assess trends for SSI rates and for compliance.

The rate of SSI – as defined by the Centers for Disease Control and Prevention – decreased by 33%, they found, from 23% to 15%. The drop occurred mainly 4 months into the vaginal cleansing portion of the study and was sustained during the following 26 months. The addition of intravenous azithromycin education did not result in any further change in the SSI rate, Dr. Quist-Nelson and associates reported in the study – the abstract for which was published in Obstetrics & Gynecology. It won a third-place prize among the papers on current clinical and basic investigation.

Compliance with the vaginal cleansing protocol increased from 60% at the start of the vaginal cleansing phase to 85% 1 year later. Azithromycin compliance rose to 75% over the third phase of the intervention.

Vaginal cleansing has received attention at Thomas Jefferson for several years. In 2017, researchers there collaborated with investigators in Italy on a systemic review and meta-analysis which concluded that women who received vaginal cleansing before cesarean delivery – most commonly with 10% povidine-iodine – had a significantly lower incidence of endometritis (Obstet Gynecol. 2017 Sep;130[3]:527-38).

A subgroup analysis showed that the benefit of vaginal cleansing was limited to “those women who have a cesarean section after their water breaks or when they’re in labor,” Dr. Quist-Nelson said.

Azithromycin similarly was found to reduce the risk of postoperative infection in women undergoing nonelective cesarean deliveries in a randomized trial published in 2016 (N Engl J Med. 2016 Sep 29;375[13]:1231-41). While the new quality improvement study did not suggest any additional benefit to intravenous azithromycin, “we continue to offer it [at our hospital] because it has been shown [in prior research] to be beneficial and because our study wasn’t [designed] to show benefit,” Dr. Quist-Nelson said.

The quality improvement intervention included hands-on training on vaginal cleansing for resident physicians and e-mail reminders for physician staff, and daily reviews for 1 week on intravenous azithromycin for resident physicians and EMR “best practice advisory” reminders for physician staff. “We also wrote a protocol available online, and put reminders in our OR notes, as well as trained the nursing staff and OR staff,” she said.

Catherine Cansino, MD, MPH, of the University of California, Davis, said in an interview that SSI rates are “problematic [in obstetrics], not only because of morbidity but also potential cost because of rehospitalization.” The study shows that vaginal cleansing “is absolutely a good target for quality improvement,” she said. “It’s promising, and very exciting to see something like this have such a dramatic positive result.” Dr. Cansino, who is a member of the Ob.Gyn News editorial advisory board, was not involved in this study.

Thomas Jefferson Hospital has had relatively high SSI rates, Dr. Quist-Nelson noted.

Dr. Quist-Nelson and coinvestigators did not report any potential conflicts of interest. Dr. Cansino also did not report any potential conflicts of interest.
 

SOURCE: Quist-Nelson J et al. Obstet. Gynecol. 2020 May;135:1S. doi: 10.1097/01.AOG.0000662876.23603.13.

Women who use copper IUDs and concurrently use menstrual cups face a higher than expected rate of IUD expulsion, results from a prospective study showed.

Citing menstrual cup use for menstrual hygiene as “increasingly popular,” researchers led by Jill Long, MD, MPH, studied women participating in a prospective contraceptive efficacy trial of two copper IUDs to evaluate the relationship between menstrual cup use and IUD expulsion over a period of 24 months. The findings were released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.

In the ongoing 3-year trial, which also was published in Obstetrics & Gynecology, 1,092 women were randomized to one of two copper IUDs. Dr. Long, project officer for the Contraceptive Clinical Trials Network, a project of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md. and colleagues conducted follow-up visits at 6 weeks after insertion in the first year, and then 3, 6, and 12 months after insertion. At the 9-month mark, the study counseling was amended to advise patients against concurrent use of the menstrual cup because of a higher risk of IUD expulsions noted in women using the cup.

Among the 1,092 women studied, 266 (24%) reported menstrual cup use. At 24 months after initiating enrollment, 43 cup users (17%) and 43 nonusers (5%) experienced expulsion (odds ratio, 3.81). Fourteen menstrual cup users with expulsion (30%) reported that the event occurred during menstrual cup removal. Dr. Long and colleagues found that, at year 1 of the study, expulsion rates among menstrual cup users and nonusers were 14% and 5%, respectively (P < .001). At the end of year 2, these rates rose to 23% and 7% (P < .001). The study won second place among abstracts in the category of current clinical and basic investigation.

“This outstanding abstract reflects an important study with results that should lead to changes in the way providers counsel patients about IUDs, namely that the risk of IUD expulsion is significantly higher in women who use menstrual cups than in those who use other menstrual hygiene products,” Eve Espey, MD, MPH, who was not affiliated with the study, said in an interview.

According to Dr. Espey, who chairs the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, key strengths of the study include its prospective methodology and the relatively large number of patients with concurrent IUD and menstrual cup use.

“A limitation is the nonrandomized design for the current study’s aim, which would require randomizing women using the IUD to menstrual cup use versus nonuse,” said Dr. Espey, who is a member of the Ob.Gyn News editorial advisory board.* “Another limitation is that only copper IUDs were used, but it is plausible that this result would apply to other IUDs as well. The study is innovative and important in being the first prospective study to evaluate the association between menstrual cup use and IUD expulsion.”

Dr. Long and two coauthors reported having no financial disclosures, but the remaining three authors reported having numerous potential conflicts of interest. Dr. Espey reported having no financial disclosures.

SOURCE: Long J et al. Obstet Gynecol. 2020 May;135.1S. doi: 10.1097/01.AOG.0000662872.89062.83.

*The article was updated on 4/28/2020.
 

Women who use copper IUDs and concurrently use menstrual cups face a higher than expected rate of IUD expulsion, results from a prospective study showed.

Citing menstrual cup use for menstrual hygiene as “increasingly popular,” researchers led by Jill Long, MD, MPH, studied women participating in a prospective contraceptive efficacy trial of two copper IUDs to evaluate the relationship between menstrual cup use and IUD expulsion over a period of 24 months. The findings were released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.

In the ongoing 3-year trial, which also was published in Obstetrics & Gynecology, 1,092 women were randomized to one of two copper IUDs. Dr. Long, project officer for the Contraceptive Clinical Trials Network, a project of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md. and colleagues conducted follow-up visits at 6 weeks after insertion in the first year, and then 3, 6, and 12 months after insertion. At the 9-month mark, the study counseling was amended to advise patients against concurrent use of the menstrual cup because of a higher risk of IUD expulsions noted in women using the cup.

Among the 1,092 women studied, 266 (24%) reported menstrual cup use. At 24 months after initiating enrollment, 43 cup users (17%) and 43 nonusers (5%) experienced expulsion (odds ratio, 3.81). Fourteen menstrual cup users with expulsion (30%) reported that the event occurred during menstrual cup removal. Dr. Long and colleagues found that, at year 1 of the study, expulsion rates among menstrual cup users and nonusers were 14% and 5%, respectively (P < .001). At the end of year 2, these rates rose to 23% and 7% (P < .001). The study won second place among abstracts in the category of current clinical and basic investigation.

“This outstanding abstract reflects an important study with results that should lead to changes in the way providers counsel patients about IUDs, namely that the risk of IUD expulsion is significantly higher in women who use menstrual cups than in those who use other menstrual hygiene products,” Eve Espey, MD, MPH, who was not affiliated with the study, said in an interview.

According to Dr. Espey, who chairs the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, key strengths of the study include its prospective methodology and the relatively large number of patients with concurrent IUD and menstrual cup use.

“A limitation is the nonrandomized design for the current study’s aim, which would require randomizing women using the IUD to menstrual cup use versus nonuse,” said Dr. Espey, who is a member of the Ob.Gyn News editorial advisory board.* “Another limitation is that only copper IUDs were used, but it is plausible that this result would apply to other IUDs as well. The study is innovative and important in being the first prospective study to evaluate the association between menstrual cup use and IUD expulsion.”

Dr. Long and two coauthors reported having no financial disclosures, but the remaining three authors reported having numerous potential conflicts of interest. Dr. Espey reported having no financial disclosures.

SOURCE: Long J et al. Obstet Gynecol. 2020 May;135.1S. doi: 10.1097/01.AOG.0000662872.89062.83.

*The article was updated on 4/28/2020.
 

Women who use copper IUDs and concurrently use menstrual cups face a higher than expected rate of IUD expulsion, results from a prospective study showed.

Citing menstrual cup use for menstrual hygiene as “increasingly popular,” researchers led by Jill Long, MD, MPH, studied women participating in a prospective contraceptive efficacy trial of two copper IUDs to evaluate the relationship between menstrual cup use and IUD expulsion over a period of 24 months. The findings were released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.

In the ongoing 3-year trial, which also was published in Obstetrics & Gynecology, 1,092 women were randomized to one of two copper IUDs. Dr. Long, project officer for the Contraceptive Clinical Trials Network, a project of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md. and colleagues conducted follow-up visits at 6 weeks after insertion in the first year, and then 3, 6, and 12 months after insertion. At the 9-month mark, the study counseling was amended to advise patients against concurrent use of the menstrual cup because of a higher risk of IUD expulsions noted in women using the cup.

Among the 1,092 women studied, 266 (24%) reported menstrual cup use. At 24 months after initiating enrollment, 43 cup users (17%) and 43 nonusers (5%) experienced expulsion (odds ratio, 3.81). Fourteen menstrual cup users with expulsion (30%) reported that the event occurred during menstrual cup removal. Dr. Long and colleagues found that, at year 1 of the study, expulsion rates among menstrual cup users and nonusers were 14% and 5%, respectively (P < .001). At the end of year 2, these rates rose to 23% and 7% (P < .001). The study won second place among abstracts in the category of current clinical and basic investigation.

“This outstanding abstract reflects an important study with results that should lead to changes in the way providers counsel patients about IUDs, namely that the risk of IUD expulsion is significantly higher in women who use menstrual cups than in those who use other menstrual hygiene products,” Eve Espey, MD, MPH, who was not affiliated with the study, said in an interview.

According to Dr. Espey, who chairs the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, key strengths of the study include its prospective methodology and the relatively large number of patients with concurrent IUD and menstrual cup use.

“A limitation is the nonrandomized design for the current study’s aim, which would require randomizing women using the IUD to menstrual cup use versus nonuse,” said Dr. Espey, who is a member of the Ob.Gyn News editorial advisory board.* “Another limitation is that only copper IUDs were used, but it is plausible that this result would apply to other IUDs as well. The study is innovative and important in being the first prospective study to evaluate the association between menstrual cup use and IUD expulsion.”

Dr. Long and two coauthors reported having no financial disclosures, but the remaining three authors reported having numerous potential conflicts of interest. Dr. Espey reported having no financial disclosures.

SOURCE: Long J et al. Obstet Gynecol. 2020 May;135.1S. doi: 10.1097/01.AOG.0000662872.89062.83.

*The article was updated on 4/28/2020.
 

The US Food and Drug Administration (FDA) granted accelerated approval to sacituzumab govitecan (Trodelvy, Immunomedics) for the treatment of metastatic triple-negative breast cancer (TNBC).

Eligible patients must have received at least two prior therapies.

TNBC is so-called because it lacks the three cellular targets present in more common forms of breast cancer. It is usually treated with chemotherapy.

Sacituzumab govitecan offers a new approach – and it has a target.

Given intravenously, the new drug is an antibody-drug conjugate in which SN-38, an active metabolite of the chemotherapy drug irinotecan (multiple brands), is coupled to a monoclonal antibody that targets an antigen that has high expression in TNBC and induces cancer cell growth.

“Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options,” observed Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research in a press statement. “There is intense interest in finding new medications” for this patient population, he added.

The new approval is based on safety and efficacy results from a phase 1/2 clinical trial of 108 patients (median age, 56 years) who had received at least two prior treatments for metastatic disease.

The overall response rate was 33% (n = 36), including three complete responses. Median duration of response was 7.7 months. Of responders, 55.6% maintained their response for at least 6 months and 16.7% for at least 12 months.

Median progression-free survival was 5.5 months, and median overall survival was 13.0 months.

The study data were published last year in the New England Journal of Medicine.

“It’s not every day that we see this sort of clinical activity in this aggressive subtype of breast cancer,” said senior study author Kevin Kalinsky, MD, in an interview at that time. He is a medical oncologist at New York–Presbyterian Hospital and Columbia University Medical Center in New York City.

The most common side effects of the new therapy were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash, and abdominal pain.

No peripheral neuropathy of grade 3 or higher was reported.

In the study, patients received sacituzumab govitecan intravenously (10 mg/kg body weight) on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

The 108 participants received a mean 18.7 doses of sacituzumab govitecan, or 9.6 cycles. The median duration of exposure was 5.1 months.

Three patients discontinued treatment because of adverse events, and two patients discontinued because of drug-related events.

The prescribing information includes a boxed warning regarding the risks of severe neutropenia and severe diarrhea. Blood cell counts should be monitored during treatment and granulocyte-colony stimulating factor (G-CSF) therapy should be considered. Anti-infective treatment should be initiated in the event of febrile neutropenia. Patients with reduced uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) activity are at increased risk for neutropenia following initiation of treatment.

The new drug can also cause hypersensitivity reactions including severe anaphylactic reactions.

Women who are pregnant should not take sacituzumab govitecan.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) granted accelerated approval to sacituzumab govitecan (Trodelvy, Immunomedics) for the treatment of metastatic triple-negative breast cancer (TNBC).

Eligible patients must have received at least two prior therapies.

TNBC is so-called because it lacks the three cellular targets present in more common forms of breast cancer. It is usually treated with chemotherapy.

Sacituzumab govitecan offers a new approach – and it has a target.

Given intravenously, the new drug is an antibody-drug conjugate in which SN-38, an active metabolite of the chemotherapy drug irinotecan (multiple brands), is coupled to a monoclonal antibody that targets an antigen that has high expression in TNBC and induces cancer cell growth.

“Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options,” observed Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research in a press statement. “There is intense interest in finding new medications” for this patient population, he added.

The new approval is based on safety and efficacy results from a phase 1/2 clinical trial of 108 patients (median age, 56 years) who had received at least two prior treatments for metastatic disease.

The overall response rate was 33% (n = 36), including three complete responses. Median duration of response was 7.7 months. Of responders, 55.6% maintained their response for at least 6 months and 16.7% for at least 12 months.

Median progression-free survival was 5.5 months, and median overall survival was 13.0 months.

The study data were published last year in the New England Journal of Medicine.

“It’s not every day that we see this sort of clinical activity in this aggressive subtype of breast cancer,” said senior study author Kevin Kalinsky, MD, in an interview at that time. He is a medical oncologist at New York–Presbyterian Hospital and Columbia University Medical Center in New York City.

The most common side effects of the new therapy were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash, and abdominal pain.

No peripheral neuropathy of grade 3 or higher was reported.

In the study, patients received sacituzumab govitecan intravenously (10 mg/kg body weight) on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

The 108 participants received a mean 18.7 doses of sacituzumab govitecan, or 9.6 cycles. The median duration of exposure was 5.1 months.

Three patients discontinued treatment because of adverse events, and two patients discontinued because of drug-related events.

The prescribing information includes a boxed warning regarding the risks of severe neutropenia and severe diarrhea. Blood cell counts should be monitored during treatment and granulocyte-colony stimulating factor (G-CSF) therapy should be considered. Anti-infective treatment should be initiated in the event of febrile neutropenia. Patients with reduced uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) activity are at increased risk for neutropenia following initiation of treatment.

The new drug can also cause hypersensitivity reactions including severe anaphylactic reactions.

Women who are pregnant should not take sacituzumab govitecan.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) granted accelerated approval to sacituzumab govitecan (Trodelvy, Immunomedics) for the treatment of metastatic triple-negative breast cancer (TNBC).

Eligible patients must have received at least two prior therapies.

TNBC is so-called because it lacks the three cellular targets present in more common forms of breast cancer. It is usually treated with chemotherapy.

Sacituzumab govitecan offers a new approach – and it has a target.

Given intravenously, the new drug is an antibody-drug conjugate in which SN-38, an active metabolite of the chemotherapy drug irinotecan (multiple brands), is coupled to a monoclonal antibody that targets an antigen that has high expression in TNBC and induces cancer cell growth.

“Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options,” observed Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research in a press statement. “There is intense interest in finding new medications” for this patient population, he added.

The new approval is based on safety and efficacy results from a phase 1/2 clinical trial of 108 patients (median age, 56 years) who had received at least two prior treatments for metastatic disease.

The overall response rate was 33% (n = 36), including three complete responses. Median duration of response was 7.7 months. Of responders, 55.6% maintained their response for at least 6 months and 16.7% for at least 12 months.

Median progression-free survival was 5.5 months, and median overall survival was 13.0 months.

The study data were published last year in the New England Journal of Medicine.

“It’s not every day that we see this sort of clinical activity in this aggressive subtype of breast cancer,” said senior study author Kevin Kalinsky, MD, in an interview at that time. He is a medical oncologist at New York–Presbyterian Hospital and Columbia University Medical Center in New York City.

The most common side effects of the new therapy were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash, and abdominal pain.

No peripheral neuropathy of grade 3 or higher was reported.

In the study, patients received sacituzumab govitecan intravenously (10 mg/kg body weight) on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

The 108 participants received a mean 18.7 doses of sacituzumab govitecan, or 9.6 cycles. The median duration of exposure was 5.1 months.

Three patients discontinued treatment because of adverse events, and two patients discontinued because of drug-related events.

The prescribing information includes a boxed warning regarding the risks of severe neutropenia and severe diarrhea. Blood cell counts should be monitored during treatment and granulocyte-colony stimulating factor (G-CSF) therapy should be considered. Anti-infective treatment should be initiated in the event of febrile neutropenia. Patients with reduced uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) activity are at increased risk for neutropenia following initiation of treatment.

The new drug can also cause hypersensitivity reactions including severe anaphylactic reactions.

Women who are pregnant should not take sacituzumab govitecan.

This article first appeared on Medscape.com.

A “strikingly high number” of women have bone marrow edema on MRI of the sacroiliac joints postpartum, according to a prospective study of 35 patients published in Annals of the Rheumatic Diseases. Postpartum sacroiliac bone marrow edema decreases over time. Its occurrence may be associated with a shorter duration of labor and a lack of epidural anesthesia, the researchers wrote.

Sacroiliac bone marrow edema in postpartum women “persists mainly in subjects older than 30 years,” noted Thomas Renson, MD, of Ghent (Belgium) University Hospital and colleagues. “When suspecting AxSpA [axial spondyloarthritis], our data indicate the need to wait at least 6 months to perform an MRI [of the sacroiliac joints] in postpartum women and, if positive, repeat the MRI after 12 months.”

Sacroiliac bone marrow edema is a hallmark of axSpA. However, recent studies of young, active people without the disease have found a high prevalence of bone marrow edema meeting the Assessment of SpondyloArthritis International Society (ASAS) definition of a positive MRI for sacroiliitis. Researchers have reported sacroiliac bone marrow edema in women during pregnancy and after childbirth, but prior studies have not assessed the trajectory of sacroiliac bone marrow edema after delivery, Dr. Renson and his colleagues said.

To study this question, the researchers recruited 35 subjects from the department of obstetrics at Ghent University Hospital. All participants were aged 18-45 years and had an uncomplicated, vaginal childbirth. The investigators excluded patients with a diagnosis of spondyloarthritis, inflammatory bowel disease, severe scoliosis, treatment with anti–tumor necrosis factor-alpha agents, any contraindication for MRI, childbirth through cesarean section, or pregnancy with more than one fetus.

Researchers performed a baseline MRI within 10 days of when patients gave birth and another MRI after 6 months. If the second MRI fulfilled the ASAS definition of a positive MRI for sacroiliitis, another MRI was performed at 12 months. Bone marrow edema was scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) method.

In all, 77% of the patients had sacroiliac bone marrow edema on MRI an average of 5 days postpartum, and 60% fulfilled the ASAS definition of a positive MRI. After 6 months, 46% had bone marrow edema on MRI, and 15% had a positive MRI according to the ASAS definition. After 12 months, MRI was positive in 12% of the subjects. There was a high prevalence of bone marrow edema “even in subjects without back pain,” the researchers said.

“Four subjects would have fulfilled the ASAS classification criteria if there was a suspicion of axSpA: Three fulfilled the ASAS definition of a positive MRI for sacroiliitis and had inflammatory back pain, [and] one had chronic back pain, a positive MRI, and skin psoriasis,” the researchers wrote.

Misdiagnosis of axSpA based on MRI findings entails risks, the authors noted. NSAIDs may be less effective in patients who do not have axSpA, and patients may be “subsequently more likely to receive ineffective biological therapy, which has significant potential side effects and encompasses high socioeconomic costs,” the investigators said.

The study was supported by an ASAS research grant. The authors declared having no competing interests.

[email protected]

SOURCE: Renson T et al. Ann Rheum Dis. 2020 Apr 16. doi: 10.1136/annrheumdis-2020-217095.

A “strikingly high number” of women have bone marrow edema on MRI of the sacroiliac joints postpartum, according to a prospective study of 35 patients published in Annals of the Rheumatic Diseases. Postpartum sacroiliac bone marrow edema decreases over time. Its occurrence may be associated with a shorter duration of labor and a lack of epidural anesthesia, the researchers wrote.

Sacroiliac bone marrow edema in postpartum women “persists mainly in subjects older than 30 years,” noted Thomas Renson, MD, of Ghent (Belgium) University Hospital and colleagues. “When suspecting AxSpA [axial spondyloarthritis], our data indicate the need to wait at least 6 months to perform an MRI [of the sacroiliac joints] in postpartum women and, if positive, repeat the MRI after 12 months.”

Sacroiliac bone marrow edema is a hallmark of axSpA. However, recent studies of young, active people without the disease have found a high prevalence of bone marrow edema meeting the Assessment of SpondyloArthritis International Society (ASAS) definition of a positive MRI for sacroiliitis. Researchers have reported sacroiliac bone marrow edema in women during pregnancy and after childbirth, but prior studies have not assessed the trajectory of sacroiliac bone marrow edema after delivery, Dr. Renson and his colleagues said.

To study this question, the researchers recruited 35 subjects from the department of obstetrics at Ghent University Hospital. All participants were aged 18-45 years and had an uncomplicated, vaginal childbirth. The investigators excluded patients with a diagnosis of spondyloarthritis, inflammatory bowel disease, severe scoliosis, treatment with anti–tumor necrosis factor-alpha agents, any contraindication for MRI, childbirth through cesarean section, or pregnancy with more than one fetus.

Researchers performed a baseline MRI within 10 days of when patients gave birth and another MRI after 6 months. If the second MRI fulfilled the ASAS definition of a positive MRI for sacroiliitis, another MRI was performed at 12 months. Bone marrow edema was scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) method.

In all, 77% of the patients had sacroiliac bone marrow edema on MRI an average of 5 days postpartum, and 60% fulfilled the ASAS definition of a positive MRI. After 6 months, 46% had bone marrow edema on MRI, and 15% had a positive MRI according to the ASAS definition. After 12 months, MRI was positive in 12% of the subjects. There was a high prevalence of bone marrow edema “even in subjects without back pain,” the researchers said.

“Four subjects would have fulfilled the ASAS classification criteria if there was a suspicion of axSpA: Three fulfilled the ASAS definition of a positive MRI for sacroiliitis and had inflammatory back pain, [and] one had chronic back pain, a positive MRI, and skin psoriasis,” the researchers wrote.

Misdiagnosis of axSpA based on MRI findings entails risks, the authors noted. NSAIDs may be less effective in patients who do not have axSpA, and patients may be “subsequently more likely to receive ineffective biological therapy, which has significant potential side effects and encompasses high socioeconomic costs,” the investigators said.

The study was supported by an ASAS research grant. The authors declared having no competing interests.

[email protected]

SOURCE: Renson T et al. Ann Rheum Dis. 2020 Apr 16. doi: 10.1136/annrheumdis-2020-217095.

A “strikingly high number” of women have bone marrow edema on MRI of the sacroiliac joints postpartum, according to a prospective study of 35 patients published in Annals of the Rheumatic Diseases. Postpartum sacroiliac bone marrow edema decreases over time. Its occurrence may be associated with a shorter duration of labor and a lack of epidural anesthesia, the researchers wrote.

Sacroiliac bone marrow edema in postpartum women “persists mainly in subjects older than 30 years,” noted Thomas Renson, MD, of Ghent (Belgium) University Hospital and colleagues. “When suspecting AxSpA [axial spondyloarthritis], our data indicate the need to wait at least 6 months to perform an MRI [of the sacroiliac joints] in postpartum women and, if positive, repeat the MRI after 12 months.”

Sacroiliac bone marrow edema is a hallmark of axSpA. However, recent studies of young, active people without the disease have found a high prevalence of bone marrow edema meeting the Assessment of SpondyloArthritis International Society (ASAS) definition of a positive MRI for sacroiliitis. Researchers have reported sacroiliac bone marrow edema in women during pregnancy and after childbirth, but prior studies have not assessed the trajectory of sacroiliac bone marrow edema after delivery, Dr. Renson and his colleagues said.

To study this question, the researchers recruited 35 subjects from the department of obstetrics at Ghent University Hospital. All participants were aged 18-45 years and had an uncomplicated, vaginal childbirth. The investigators excluded patients with a diagnosis of spondyloarthritis, inflammatory bowel disease, severe scoliosis, treatment with anti–tumor necrosis factor-alpha agents, any contraindication for MRI, childbirth through cesarean section, or pregnancy with more than one fetus.

Researchers performed a baseline MRI within 10 days of when patients gave birth and another MRI after 6 months. If the second MRI fulfilled the ASAS definition of a positive MRI for sacroiliitis, another MRI was performed at 12 months. Bone marrow edema was scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) method.

In all, 77% of the patients had sacroiliac bone marrow edema on MRI an average of 5 days postpartum, and 60% fulfilled the ASAS definition of a positive MRI. After 6 months, 46% had bone marrow edema on MRI, and 15% had a positive MRI according to the ASAS definition. After 12 months, MRI was positive in 12% of the subjects. There was a high prevalence of bone marrow edema “even in subjects without back pain,” the researchers said.

“Four subjects would have fulfilled the ASAS classification criteria if there was a suspicion of axSpA: Three fulfilled the ASAS definition of a positive MRI for sacroiliitis and had inflammatory back pain, [and] one had chronic back pain, a positive MRI, and skin psoriasis,” the researchers wrote.

Misdiagnosis of axSpA based on MRI findings entails risks, the authors noted. NSAIDs may be less effective in patients who do not have axSpA, and patients may be “subsequently more likely to receive ineffective biological therapy, which has significant potential side effects and encompasses high socioeconomic costs,” the investigators said.

The study was supported by an ASAS research grant. The authors declared having no competing interests.

[email protected]

SOURCE: Renson T et al. Ann Rheum Dis. 2020 Apr 16. doi: 10.1136/annrheumdis-2020-217095.

Pemphigoid gestationis
 

Pemphigoid gestationis, which is also known as herpes gestationis or gestational pemphigoid, is a rare, autoimmune vesiculobullous eruption that occurs during the third trimester of pregnancy or in the postpartum period.

Holly Hanson MD, Associated Skin Care Specialists, Eden Prairie, Minn.

It typically presents with the abrupt onset of very pruritic urticarial plaques and papules, which start around the umbilicus and then spread to involve the trunk and extremities. The papules and plaques evolve to generalized tense blisters, which typically spare the face, palms, soles, and mucous membranes. Half of affected patients may present in an atypical distribution involving the extremities, palms, or soles. Patients may be at an increased risk for the development of Graves disease.

The cause of pemphigoid gestationis is a factor known as “herpes gestationis factor” that induces C3 deposition along the dermal-epidermal junction. As in bullous pemphigoid, patients with pemphigoid gestationis have antibodies to a transmembrane hemidesmosomal protein called BPAG2/BP180/collagen XVII.

Holly Hanson MD, Associated Skin Care Specialists, Eden Prairie, Minn.

Three-quarters of patients worsen at the time of delivery and up to 10% of newborns will have bullous lesions secondary to placental transfer of antibodies. In most cases, lesions will spontaneously resolve over a few weeks following delivery. Recurrence with future pregnancies is common, with severity increasing with each pregnancy. Recurrence with menstruation and with the use of oral contraceptives can also occur. Although there is no increase in maternal mortality, onset in the first or second trimester and presence of blisters is associated with decreased gestational age of baby at delivery and lower-birth-weight infants. There is no increase in fetal mortality.

Histopathology reveals a subepidermal vesicle and perivascular infiltrate consisting of lymphocytes and eosinophils. Diagnosis can be confirmed with direct immunofluorescence showing C3 in a linear band along the basement membrane zone. IgG may be present as well. Complement added indirect immunofluorescence reveals circulating anti–basement zone IgG, which allows differentiation from pruritic urticarial papules and plaques of pregnancy.

Treatment for localized disease includes class I topical steroids and oral antihistamines. More severe cases require systemic corticosteroid treatment. Systemic steroids may cause lower-birth-weight infants.

This case and the photos were submitted by Dr. Hanson of Associated Skin Care Specialists in Eden Prairie, Minn. The case was edited by Donna Bilu Martin, MD.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

Pemphigoid gestationis
 

Pemphigoid gestationis, which is also known as herpes gestationis or gestational pemphigoid, is a rare, autoimmune vesiculobullous eruption that occurs during the third trimester of pregnancy or in the postpartum period.

Holly Hanson MD, Associated Skin Care Specialists, Eden Prairie, Minn.

It typically presents with the abrupt onset of very pruritic urticarial plaques and papules, which start around the umbilicus and then spread to involve the trunk and extremities. The papules and plaques evolve to generalized tense blisters, which typically spare the face, palms, soles, and mucous membranes. Half of affected patients may present in an atypical distribution involving the extremities, palms, or soles. Patients may be at an increased risk for the development of Graves disease.

The cause of pemphigoid gestationis is a factor known as “herpes gestationis factor” that induces C3 deposition along the dermal-epidermal junction. As in bullous pemphigoid, patients with pemphigoid gestationis have antibodies to a transmembrane hemidesmosomal protein called BPAG2/BP180/collagen XVII.

Holly Hanson MD, Associated Skin Care Specialists, Eden Prairie, Minn.

Three-quarters of patients worsen at the time of delivery and up to 10% of newborns will have bullous lesions secondary to placental transfer of antibodies. In most cases, lesions will spontaneously resolve over a few weeks following delivery. Recurrence with future pregnancies is common, with severity increasing with each pregnancy. Recurrence with menstruation and with the use of oral contraceptives can also occur. Although there is no increase in maternal mortality, onset in the first or second trimester and presence of blisters is associated with decreased gestational age of baby at delivery and lower-birth-weight infants. There is no increase in fetal mortality.

Histopathology reveals a subepidermal vesicle and perivascular infiltrate consisting of lymphocytes and eosinophils. Diagnosis can be confirmed with direct immunofluorescence showing C3 in a linear band along the basement membrane zone. IgG may be present as well. Complement added indirect immunofluorescence reveals circulating anti–basement zone IgG, which allows differentiation from pruritic urticarial papules and plaques of pregnancy.

Treatment for localized disease includes class I topical steroids and oral antihistamines. More severe cases require systemic corticosteroid treatment. Systemic steroids may cause lower-birth-weight infants.

This case and the photos were submitted by Dr. Hanson of Associated Skin Care Specialists in Eden Prairie, Minn. The case was edited by Donna Bilu Martin, MD.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

Pemphigoid gestationis
 

Pemphigoid gestationis, which is also known as herpes gestationis or gestational pemphigoid, is a rare, autoimmune vesiculobullous eruption that occurs during the third trimester of pregnancy or in the postpartum period.

Holly Hanson MD, Associated Skin Care Specialists, Eden Prairie, Minn.

It typically presents with the abrupt onset of very pruritic urticarial plaques and papules, which start around the umbilicus and then spread to involve the trunk and extremities. The papules and plaques evolve to generalized tense blisters, which typically spare the face, palms, soles, and mucous membranes. Half of affected patients may present in an atypical distribution involving the extremities, palms, or soles. Patients may be at an increased risk for the development of Graves disease.

The cause of pemphigoid gestationis is a factor known as “herpes gestationis factor” that induces C3 deposition along the dermal-epidermal junction. As in bullous pemphigoid, patients with pemphigoid gestationis have antibodies to a transmembrane hemidesmosomal protein called BPAG2/BP180/collagen XVII.

Holly Hanson MD, Associated Skin Care Specialists, Eden Prairie, Minn.

Three-quarters of patients worsen at the time of delivery and up to 10% of newborns will have bullous lesions secondary to placental transfer of antibodies. In most cases, lesions will spontaneously resolve over a few weeks following delivery. Recurrence with future pregnancies is common, with severity increasing with each pregnancy. Recurrence with menstruation and with the use of oral contraceptives can also occur. Although there is no increase in maternal mortality, onset in the first or second trimester and presence of blisters is associated with decreased gestational age of baby at delivery and lower-birth-weight infants. There is no increase in fetal mortality.

Histopathology reveals a subepidermal vesicle and perivascular infiltrate consisting of lymphocytes and eosinophils. Diagnosis can be confirmed with direct immunofluorescence showing C3 in a linear band along the basement membrane zone. IgG may be present as well. Complement added indirect immunofluorescence reveals circulating anti–basement zone IgG, which allows differentiation from pruritic urticarial papules and plaques of pregnancy.

Treatment for localized disease includes class I topical steroids and oral antihistamines. More severe cases require systemic corticosteroid treatment. Systemic steroids may cause lower-birth-weight infants.

This case and the photos were submitted by Dr. Hanson of Associated Skin Care Specialists in Eden Prairie, Minn. The case was edited by Donna Bilu Martin, MD.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

The U.S. Food and Drug Administration has approved the oral therapy tucatinib (Tukysa, Seattle Genetics) for the treatment of advanced HER2-positive breast cancer. This is the first new drug approved under Project Orbis, an international collaboration.

Tucatinib, which is a small-molecule tyrosine kinase inhibitor, is approved in combination with trastuzumab and capecitabine to treat patients who have received one or more prior treatments for advanced disease.

The FDA collaborated with the regulatory authorities of Australia, Canada, Singapore, and Switzerland on this review. However, only the FDA has approved tucatinib; the application is still under review at the other agencies.

While working with Project Orbis in 2019, the FDA granted an accelerated, conditional approval to a drug combination that included previously approved agents.

“The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international collaborators,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a statement.

Collaboration among regulators may allow patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions, according to the FDA.

The new drug is a “valuable addition” to the roster of treatments for advanced HER2-positive breast cancer, said study investigator Eric Winer, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, in a company press statement.

“With highly significant and clinically important results for overall and progression-free survival, the addition of [tucatinib] to trastuzumab and capecitabine has the potential to become a standard of care for people with HER2-positive metastatic breast cancer after having received one or more previous anti-HER2 therapies in the metastatic setting,” he said.

The new approval is based on safety and efficacy results from the phase 2 HER2CLIMB trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine.

Nearly half (48%) of patients in the study had brain metastases at the start of the trial. The primary outcome measure was progression-free survival (PFS). All patients received trastuzumab and capecitabine and were randomly assigned to either tucatinib or placebo.

Median PFS in the tucatinib patient group was 7.8 months, compared with 5.6 months in the placebo group. The PFS results in the subgroup of patients with brain metastases were nearly the same.

Median overall survival in the tucatinib patient group was 21.9 months versus 17.4 months in the placebo group.

The new drug is a rare success in the treatment of breast cancer brain metastases, said Jawad Fares, MD, of Northwestern University, Chicago, Illinois, who spoke to Medscape Medical News when the phase 3 trial data were first presented at the 2019 San Antonio Breast Cancer Symposium.

“Outcomes in the field have been pretty dismal,” summarized Fares, who was not involved in the study.

The results of the HER2CLIMB study, which was funded by Seattle Genetics, were published in the New England Journal of Medicine last year.

According to the FDA, common side effects with tucatinib were diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Tucatinib can cause serious side effects, including diarrhea associated with dehydration, acute kidney injury, and death. Health care professionals should start antidiarrheals as clinically indicated if diarrhea occurs and should interrupt treatment or reduce the dosage. Tucatinib can also cause severe hepatotoxicity; patients should be monitored with liver tests.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved the oral therapy tucatinib (Tukysa, Seattle Genetics) for the treatment of advanced HER2-positive breast cancer. This is the first new drug approved under Project Orbis, an international collaboration.

Tucatinib, which is a small-molecule tyrosine kinase inhibitor, is approved in combination with trastuzumab and capecitabine to treat patients who have received one or more prior treatments for advanced disease.

The FDA collaborated with the regulatory authorities of Australia, Canada, Singapore, and Switzerland on this review. However, only the FDA has approved tucatinib; the application is still under review at the other agencies.

While working with Project Orbis in 2019, the FDA granted an accelerated, conditional approval to a drug combination that included previously approved agents.

“The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international collaborators,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a statement.

Collaboration among regulators may allow patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions, according to the FDA.

The new drug is a “valuable addition” to the roster of treatments for advanced HER2-positive breast cancer, said study investigator Eric Winer, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, in a company press statement.

“With highly significant and clinically important results for overall and progression-free survival, the addition of [tucatinib] to trastuzumab and capecitabine has the potential to become a standard of care for people with HER2-positive metastatic breast cancer after having received one or more previous anti-HER2 therapies in the metastatic setting,” he said.

The new approval is based on safety and efficacy results from the phase 2 HER2CLIMB trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine.

Nearly half (48%) of patients in the study had brain metastases at the start of the trial. The primary outcome measure was progression-free survival (PFS). All patients received trastuzumab and capecitabine and were randomly assigned to either tucatinib or placebo.

Median PFS in the tucatinib patient group was 7.8 months, compared with 5.6 months in the placebo group. The PFS results in the subgroup of patients with brain metastases were nearly the same.

Median overall survival in the tucatinib patient group was 21.9 months versus 17.4 months in the placebo group.

The new drug is a rare success in the treatment of breast cancer brain metastases, said Jawad Fares, MD, of Northwestern University, Chicago, Illinois, who spoke to Medscape Medical News when the phase 3 trial data were first presented at the 2019 San Antonio Breast Cancer Symposium.

“Outcomes in the field have been pretty dismal,” summarized Fares, who was not involved in the study.

The results of the HER2CLIMB study, which was funded by Seattle Genetics, were published in the New England Journal of Medicine last year.

According to the FDA, common side effects with tucatinib were diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Tucatinib can cause serious side effects, including diarrhea associated with dehydration, acute kidney injury, and death. Health care professionals should start antidiarrheals as clinically indicated if diarrhea occurs and should interrupt treatment or reduce the dosage. Tucatinib can also cause severe hepatotoxicity; patients should be monitored with liver tests.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved the oral therapy tucatinib (Tukysa, Seattle Genetics) for the treatment of advanced HER2-positive breast cancer. This is the first new drug approved under Project Orbis, an international collaboration.

Tucatinib, which is a small-molecule tyrosine kinase inhibitor, is approved in combination with trastuzumab and capecitabine to treat patients who have received one or more prior treatments for advanced disease.

The FDA collaborated with the regulatory authorities of Australia, Canada, Singapore, and Switzerland on this review. However, only the FDA has approved tucatinib; the application is still under review at the other agencies.

While working with Project Orbis in 2019, the FDA granted an accelerated, conditional approval to a drug combination that included previously approved agents.

“The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international collaborators,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a statement.

Collaboration among regulators may allow patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions, according to the FDA.

The new drug is a “valuable addition” to the roster of treatments for advanced HER2-positive breast cancer, said study investigator Eric Winer, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, in a company press statement.

“With highly significant and clinically important results for overall and progression-free survival, the addition of [tucatinib] to trastuzumab and capecitabine has the potential to become a standard of care for people with HER2-positive metastatic breast cancer after having received one or more previous anti-HER2 therapies in the metastatic setting,” he said.

The new approval is based on safety and efficacy results from the phase 2 HER2CLIMB trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine.

Nearly half (48%) of patients in the study had brain metastases at the start of the trial. The primary outcome measure was progression-free survival (PFS). All patients received trastuzumab and capecitabine and were randomly assigned to either tucatinib or placebo.

Median PFS in the tucatinib patient group was 7.8 months, compared with 5.6 months in the placebo group. The PFS results in the subgroup of patients with brain metastases were nearly the same.

Median overall survival in the tucatinib patient group was 21.9 months versus 17.4 months in the placebo group.

The new drug is a rare success in the treatment of breast cancer brain metastases, said Jawad Fares, MD, of Northwestern University, Chicago, Illinois, who spoke to Medscape Medical News when the phase 3 trial data were first presented at the 2019 San Antonio Breast Cancer Symposium.

“Outcomes in the field have been pretty dismal,” summarized Fares, who was not involved in the study.

The results of the HER2CLIMB study, which was funded by Seattle Genetics, were published in the New England Journal of Medicine last year.

According to the FDA, common side effects with tucatinib were diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Tucatinib can cause serious side effects, including diarrhea associated with dehydration, acute kidney injury, and death. Health care professionals should start antidiarrheals as clinically indicated if diarrhea occurs and should interrupt treatment or reduce the dosage. Tucatinib can also cause severe hepatotoxicity; patients should be monitored with liver tests.

This article first appeared on Medscape.com.