Ob.Gyn. News

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.

Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m²) or are overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity.

Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.

Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.

This weight-loss drug is currently under review by the European Medicines Agency.

Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.


 

‘Game changer’ drug tested in STEP clinical trial program

The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.

The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.

As previously reported by this news organization, all trials were in adults with overweight or obesity:

•  was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
•  was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
•  was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
•  was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).

In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.

The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.

The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.

A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”

“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
 

Welcome Addition, But Will Insurance Coverage, Price Thwart Access?

Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”

The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.

And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.

Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.

However, insurance coverage and price could block uptake.

“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”

“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.

“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”

However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”

“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.

Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.

The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.

And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
 

CVOT and oral format trials for obesity on the horizon

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.

And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.

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

This article was updated 6/7/21.

The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.

Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m²) or are overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity.

Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.

Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.

This weight-loss drug is currently under review by the European Medicines Agency.

Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.


 

‘Game changer’ drug tested in STEP clinical trial program

The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.

The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.

As previously reported by this news organization, all trials were in adults with overweight or obesity:

•  was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
•  was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
•  was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
•  was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).

In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.

The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.

The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.

A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”

“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
 

Welcome Addition, But Will Insurance Coverage, Price Thwart Access?

Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”

The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.

And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.

Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.

However, insurance coverage and price could block uptake.

“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”

“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.

“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”

However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”

“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.

Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.

The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.

And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
 

CVOT and oral format trials for obesity on the horizon

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.

And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.

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

This article was updated 6/7/21.

The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.

Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m²) or are overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity.

Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.

Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.

This weight-loss drug is currently under review by the European Medicines Agency.

Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.


 

‘Game changer’ drug tested in STEP clinical trial program

The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.

The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.

As previously reported by this news organization, all trials were in adults with overweight or obesity:

•  was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
•  was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
•  was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
•  was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).

In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.

The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.

The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.

A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”

“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
 

Welcome Addition, But Will Insurance Coverage, Price Thwart Access?

Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”

The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.

And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.

Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.

However, insurance coverage and price could block uptake.

“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”

“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.

“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”

However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”

“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.

Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.

The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.

And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
 

CVOT and oral format trials for obesity on the horizon

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.

And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.

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

This article was updated 6/7/21.

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

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

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

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

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

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

With the COVID-19 pandemic, already high rates of suicide, depression, and burnout among physicians became even more acute. Yet, 3 years after the Federation of State Medical Boards issued recommendations on what questions about mental health status license applications should – or mostly should not – include, only North Carolina fully complies with all four recommendations, and most states comply with two or fewer, a study of state medical board applications has found (JAMA. 2021 May 18;325[19];2017-8).

Questions about mental health history or “its hypothetical effect on competency,” violate the Americans with Disabilities Act, the study authors stated. In a research letter to JAMA, the authors also reported that five state boards do not comply with any of the FSMB recommendations. Twenty-four states comply with three of the four recommendations.

Overall, the mean consistency score was 2.1, which means state medical licensing applications typically run afoul of the Americans With Disabilities Act when it comes to mental health history of applicants.

“No one should ever wonder, ‘Will I lose my job, or should I get help?’ ” said co–senior author Jessica A. Gold, MD, MS, a psychiatrist at Washington University in St. Louis. “This should absolutely never be a question on someone’s mind. And the fact that it is, in medicine, is a problem that needs to be solved. I hope that people are beginning to see that, and we can make a change to get people the help they need before it is too late.”
 

High rates of depression, suicide

She noted that before COVID-19, physicians already had higher rates of depression, burnout, and suicide than the general population. “Over COVID-19, it has become clear that the mental health of physicians has become additionally compounded,” Dr. Gold said.

One study found that physicians had a 44% higher rate of suicide (PLoS One. 2019 Dec;14[12]:e0226361), but they’re notoriously reluctant to seek out mental health care. A 2017 study reported that 40% of physicians would be reluctant to seek mental health care because of concerns about their licensure (Mayo Clin Proc. 2017;92[10]:1486-93).

As the pandemic went on, Dr. Gold and her colleagues decided to study whether state boards had improved their compliance with the FSMB recommendations issued in 2018. Those recommendations include these four limitations regarding questions about mental health conditions on license applications:

• Include only when they result in impairment.
• Include only when the mental health conditions are current – that is, when they’ve occurred within the past 2 years.
• Provide safe haven nonreporting – that is, allow physicians to not report previously diagnosed and treated mental health conditions if they’re being monitored and are in good standing with a physician health program.
• Include supportive or nonjudgmental language about seeking mental health care.

The study considered board applications that had questions about mental health status as consistent with the first three recommendations. Seventeen states complied.

Thirty-nine state boards complied with the first recommendation regarding impairment; 41 with the second recommendation about near-term history; 25 with safe-haven nonreporting. Only eight states were consistent with the recommendation on supportive language.

The ADA limits inquiries about an applicant’s impairment to only current conditions. In a 2017 study, only 21 state boards had limited questions to current impairment. “This is a significant improvement, but this still means the rest of the states are violating an actual law,” Dr. Gold said. “Another plus is that 17 states asked no questions at all that could require mental health disclosure. This, too is significant because it highlights change in thinking.”

But still, the fact that five states didn’t comply with any recommendation and only one followed all of them is “utterly unacceptable,” Dr. Gold said. “Instead, we should have universal adoption of FSMB recommendations.”
 

Time to remove stigma

Michael F. Myers, MD, a clinical psychiatrist at the State University of New York, Brooklyn, said removing the stigma of seeking help for mental health conditions is especially important for physicians. He’s written several books about physician mental health, including his latest, “Becoming a Doctor’s Doctor: A Memoir.”

“I would say at least 15% of the families that I interviewed who lost a physician loved one to suicide have said the doctor was petrified of going for professional help because of fears of what this could do to their medical license,” he said. “It is extremely important that those licensing questions will be either brought up to speed, or ­– the ones that are clearly violating the ADA – that they be removed.”

Applications for hospital privileges can also run afoul of the same ADA standard, Dr. Myers added. “Physicians have told me that when they go to get medical privileges at a medical center, they get asked all kinds of questions that are outdated, that are intrusive, that violate the ADA,” he said.

Credentialing is another area that Dr. Gold and her colleagues are interested in studying, she said. “Sometimes the licensing applications can be fine, but then the hospital someone is applying to work at can ask the same illegal questions anyway,” she said. “So it doesn’t matter that the state fixed the problem because the hospital asked them anyway. You feel your job is at risk in the same way, so you still don’t get help.”

Dr. Gold and Dr. Myers have no relevant financial relationships to disclose.

With the COVID-19 pandemic, already high rates of suicide, depression, and burnout among physicians became even more acute. Yet, 3 years after the Federation of State Medical Boards issued recommendations on what questions about mental health status license applications should – or mostly should not – include, only North Carolina fully complies with all four recommendations, and most states comply with two or fewer, a study of state medical board applications has found (JAMA. 2021 May 18;325[19];2017-8).

Questions about mental health history or “its hypothetical effect on competency,” violate the Americans with Disabilities Act, the study authors stated. In a research letter to JAMA, the authors also reported that five state boards do not comply with any of the FSMB recommendations. Twenty-four states comply with three of the four recommendations.

Overall, the mean consistency score was 2.1, which means state medical licensing applications typically run afoul of the Americans With Disabilities Act when it comes to mental health history of applicants.

“No one should ever wonder, ‘Will I lose my job, or should I get help?’ ” said co–senior author Jessica A. Gold, MD, MS, a psychiatrist at Washington University in St. Louis. “This should absolutely never be a question on someone’s mind. And the fact that it is, in medicine, is a problem that needs to be solved. I hope that people are beginning to see that, and we can make a change to get people the help they need before it is too late.”
 

High rates of depression, suicide

She noted that before COVID-19, physicians already had higher rates of depression, burnout, and suicide than the general population. “Over COVID-19, it has become clear that the mental health of physicians has become additionally compounded,” Dr. Gold said.

One study found that physicians had a 44% higher rate of suicide (PLoS One. 2019 Dec;14[12]:e0226361), but they’re notoriously reluctant to seek out mental health care. A 2017 study reported that 40% of physicians would be reluctant to seek mental health care because of concerns about their licensure (Mayo Clin Proc. 2017;92[10]:1486-93).

As the pandemic went on, Dr. Gold and her colleagues decided to study whether state boards had improved their compliance with the FSMB recommendations issued in 2018. Those recommendations include these four limitations regarding questions about mental health conditions on license applications:

• Include only when they result in impairment.
• Include only when the mental health conditions are current – that is, when they’ve occurred within the past 2 years.
• Provide safe haven nonreporting – that is, allow physicians to not report previously diagnosed and treated mental health conditions if they’re being monitored and are in good standing with a physician health program.
• Include supportive or nonjudgmental language about seeking mental health care.

The study considered board applications that had questions about mental health status as consistent with the first three recommendations. Seventeen states complied.

Thirty-nine state boards complied with the first recommendation regarding impairment; 41 with the second recommendation about near-term history; 25 with safe-haven nonreporting. Only eight states were consistent with the recommendation on supportive language.

The ADA limits inquiries about an applicant’s impairment to only current conditions. In a 2017 study, only 21 state boards had limited questions to current impairment. “This is a significant improvement, but this still means the rest of the states are violating an actual law,” Dr. Gold said. “Another plus is that 17 states asked no questions at all that could require mental health disclosure. This, too is significant because it highlights change in thinking.”

But still, the fact that five states didn’t comply with any recommendation and only one followed all of them is “utterly unacceptable,” Dr. Gold said. “Instead, we should have universal adoption of FSMB recommendations.”
 

Time to remove stigma

Michael F. Myers, MD, a clinical psychiatrist at the State University of New York, Brooklyn, said removing the stigma of seeking help for mental health conditions is especially important for physicians. He’s written several books about physician mental health, including his latest, “Becoming a Doctor’s Doctor: A Memoir.”

“I would say at least 15% of the families that I interviewed who lost a physician loved one to suicide have said the doctor was petrified of going for professional help because of fears of what this could do to their medical license,” he said. “It is extremely important that those licensing questions will be either brought up to speed, or ­– the ones that are clearly violating the ADA – that they be removed.”

Applications for hospital privileges can also run afoul of the same ADA standard, Dr. Myers added. “Physicians have told me that when they go to get medical privileges at a medical center, they get asked all kinds of questions that are outdated, that are intrusive, that violate the ADA,” he said.

Credentialing is another area that Dr. Gold and her colleagues are interested in studying, she said. “Sometimes the licensing applications can be fine, but then the hospital someone is applying to work at can ask the same illegal questions anyway,” she said. “So it doesn’t matter that the state fixed the problem because the hospital asked them anyway. You feel your job is at risk in the same way, so you still don’t get help.”

Dr. Gold and Dr. Myers have no relevant financial relationships to disclose.

With the COVID-19 pandemic, already high rates of suicide, depression, and burnout among physicians became even more acute. Yet, 3 years after the Federation of State Medical Boards issued recommendations on what questions about mental health status license applications should – or mostly should not – include, only North Carolina fully complies with all four recommendations, and most states comply with two or fewer, a study of state medical board applications has found (JAMA. 2021 May 18;325[19];2017-8).

Questions about mental health history or “its hypothetical effect on competency,” violate the Americans with Disabilities Act, the study authors stated. In a research letter to JAMA, the authors also reported that five state boards do not comply with any of the FSMB recommendations. Twenty-four states comply with three of the four recommendations.

Overall, the mean consistency score was 2.1, which means state medical licensing applications typically run afoul of the Americans With Disabilities Act when it comes to mental health history of applicants.

“No one should ever wonder, ‘Will I lose my job, or should I get help?’ ” said co–senior author Jessica A. Gold, MD, MS, a psychiatrist at Washington University in St. Louis. “This should absolutely never be a question on someone’s mind. And the fact that it is, in medicine, is a problem that needs to be solved. I hope that people are beginning to see that, and we can make a change to get people the help they need before it is too late.”
 

High rates of depression, suicide

She noted that before COVID-19, physicians already had higher rates of depression, burnout, and suicide than the general population. “Over COVID-19, it has become clear that the mental health of physicians has become additionally compounded,” Dr. Gold said.

One study found that physicians had a 44% higher rate of suicide (PLoS One. 2019 Dec;14[12]:e0226361), but they’re notoriously reluctant to seek out mental health care. A 2017 study reported that 40% of physicians would be reluctant to seek mental health care because of concerns about their licensure (Mayo Clin Proc. 2017;92[10]:1486-93).

As the pandemic went on, Dr. Gold and her colleagues decided to study whether state boards had improved their compliance with the FSMB recommendations issued in 2018. Those recommendations include these four limitations regarding questions about mental health conditions on license applications:

• Include only when they result in impairment.
• Include only when the mental health conditions are current – that is, when they’ve occurred within the past 2 years.
• Provide safe haven nonreporting – that is, allow physicians to not report previously diagnosed and treated mental health conditions if they’re being monitored and are in good standing with a physician health program.
• Include supportive or nonjudgmental language about seeking mental health care.

The study considered board applications that had questions about mental health status as consistent with the first three recommendations. Seventeen states complied.

Thirty-nine state boards complied with the first recommendation regarding impairment; 41 with the second recommendation about near-term history; 25 with safe-haven nonreporting. Only eight states were consistent with the recommendation on supportive language.

The ADA limits inquiries about an applicant’s impairment to only current conditions. In a 2017 study, only 21 state boards had limited questions to current impairment. “This is a significant improvement, but this still means the rest of the states are violating an actual law,” Dr. Gold said. “Another plus is that 17 states asked no questions at all that could require mental health disclosure. This, too is significant because it highlights change in thinking.”

But still, the fact that five states didn’t comply with any recommendation and only one followed all of them is “utterly unacceptable,” Dr. Gold said. “Instead, we should have universal adoption of FSMB recommendations.”
 

Time to remove stigma

Michael F. Myers, MD, a clinical psychiatrist at the State University of New York, Brooklyn, said removing the stigma of seeking help for mental health conditions is especially important for physicians. He’s written several books about physician mental health, including his latest, “Becoming a Doctor’s Doctor: A Memoir.”

“I would say at least 15% of the families that I interviewed who lost a physician loved one to suicide have said the doctor was petrified of going for professional help because of fears of what this could do to their medical license,” he said. “It is extremely important that those licensing questions will be either brought up to speed, or ­– the ones that are clearly violating the ADA – that they be removed.”

Applications for hospital privileges can also run afoul of the same ADA standard, Dr. Myers added. “Physicians have told me that when they go to get medical privileges at a medical center, they get asked all kinds of questions that are outdated, that are intrusive, that violate the ADA,” he said.

Credentialing is another area that Dr. Gold and her colleagues are interested in studying, she said. “Sometimes the licensing applications can be fine, but then the hospital someone is applying to work at can ask the same illegal questions anyway,” she said. “So it doesn’t matter that the state fixed the problem because the hospital asked them anyway. You feel your job is at risk in the same way, so you still don’t get help.”

Dr. Gold and Dr. Myers have no relevant financial relationships to disclose.

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

Black patients experienced more moderate to severe violent trauma during pregnancy than did non-Black patients at a single Baltimore institution, according to a small retrospective cohort study presented in a poster at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

“Trauma is the leading nonobstetric cause of death in pregnant women,” and Black communities are at a disproportionately greater risk of trauma, Rebecca H. Jessel, MD, of Icahn School of Medicine at Mount Sinai in New York, and associates wrote in their poster.

The study’s findings raise research questions that need more exploration, according to Neel Shah, MD, assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, and founding director of the Delivery Decisions Initiative at Harvard’s Ariadne Labs.

“This is an interesting study that opens a line of inquiry into how trauma may impact the pregnancies of those who are Black differently,” Dr. Shah, who was not involved in the research, said in an interview. “The observed disparity is consistent with the racial inequities in outcomes we see across obstetric outcomes and requires further research into the causes and solutions.”

The researchers retrospectively reviewed all pregnant patients treated between 2015 and 2018 at the University of Maryland’s R Adams Cowley Shock Trauma Center in Baltimore. In addition to maternal demographics, details about the delivery, and perinatal outcomes, the researchers noted whether the trauma was violent, such as assault, or nonviolent, such as motor vehicle accidents. Moderate to severe trauma was defined as an injury severity score of at least 9.

Among 3,536 women aged 15-49 treated at the shock trauma center, 62 were pregnant, and 71% of these women were Black. Nineteen percent were White patients, 5% were Asian patients, and 5% were of a different race/ethnicity. Black patients were, on average, 27 years old at the time of the trauma. Non-Black patients were, on average, 25 years old. The average gestational age at the time of trauma was 25 weeks, 3 days in Black women and 23 weeks, 4 days in non-Black women.

The most common cause of trauma was a car accident, implicated in 56% of the trauma cases. Assault was the next most common cause of trauma, making up nearly a quarter (23%) of cases. The other injuries came from accidents (16%) or inhalation (5%). The average injury severity score was 4.7, with a mild injury for 76% of patients and a moderate to severe injury in 24%.

The researchers then compared the mechanisms and severity of injuries between Black and non-Black patients. The severity of trauma was similar between the two groups: Seventy-five percent of Black patients and 78% of non-Black patients had mild trauma with injury severity scores below 9. However, assault or another violent form of trauma was more likely to occur to Black patients than to non-Black patients. More than a quarter (27%) of Black patients experienced violent trauma, compared to 11% of non-Black patients.

“It is very notable that among pregnant people who experience trauma, obstetric complications leading to preterm delivery were observed much more often for those who are Black,” Dr. Shah said. “A case series to understand the underlying causes could be very valuable.”

Black patients delivered an average 59 days (8 weeks, 3 days) after the trauma compared to an average 83 days (11 weeks, 6 days) for non-Black patients, but the difference was not statistically significant. However, preterm birth was more likely in non-Black patients (83%) than in Black patients (78%). A similar proportion of deliveries were preterm in Black (57%) and non-Black (56%) patients.

Though the poster did not show the data, the researchers wrote that Black women who experienced moderate to severe trauma after 24 weeks’ gestational age either had a preterm birth or a fetal demise.

Though the study findings warrant deeper investigation, the study has substantial limitations.

“It is challenging to generalize from this study because the sample size is small and it is from a single institution,” Dr. Shah said. “It does not appear to be adequately powered to draw statistically significant conclusions. In particular, the data are not adequate to support the authors’ statement that Black people are more likely to experience the forms of described trauma generally.”

The authors and Dr. Shah reported no disclosures.

Black patients experienced more moderate to severe violent trauma during pregnancy than did non-Black patients at a single Baltimore institution, according to a small retrospective cohort study presented in a poster at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

“Trauma is the leading nonobstetric cause of death in pregnant women,” and Black communities are at a disproportionately greater risk of trauma, Rebecca H. Jessel, MD, of Icahn School of Medicine at Mount Sinai in New York, and associates wrote in their poster.

The study’s findings raise research questions that need more exploration, according to Neel Shah, MD, assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, and founding director of the Delivery Decisions Initiative at Harvard’s Ariadne Labs.

“This is an interesting study that opens a line of inquiry into how trauma may impact the pregnancies of those who are Black differently,” Dr. Shah, who was not involved in the research, said in an interview. “The observed disparity is consistent with the racial inequities in outcomes we see across obstetric outcomes and requires further research into the causes and solutions.”

The researchers retrospectively reviewed all pregnant patients treated between 2015 and 2018 at the University of Maryland’s R Adams Cowley Shock Trauma Center in Baltimore. In addition to maternal demographics, details about the delivery, and perinatal outcomes, the researchers noted whether the trauma was violent, such as assault, or nonviolent, such as motor vehicle accidents. Moderate to severe trauma was defined as an injury severity score of at least 9.

Among 3,536 women aged 15-49 treated at the shock trauma center, 62 were pregnant, and 71% of these women were Black. Nineteen percent were White patients, 5% were Asian patients, and 5% were of a different race/ethnicity. Black patients were, on average, 27 years old at the time of the trauma. Non-Black patients were, on average, 25 years old. The average gestational age at the time of trauma was 25 weeks, 3 days in Black women and 23 weeks, 4 days in non-Black women.

The most common cause of trauma was a car accident, implicated in 56% of the trauma cases. Assault was the next most common cause of trauma, making up nearly a quarter (23%) of cases. The other injuries came from accidents (16%) or inhalation (5%). The average injury severity score was 4.7, with a mild injury for 76% of patients and a moderate to severe injury in 24%.

The researchers then compared the mechanisms and severity of injuries between Black and non-Black patients. The severity of trauma was similar between the two groups: Seventy-five percent of Black patients and 78% of non-Black patients had mild trauma with injury severity scores below 9. However, assault or another violent form of trauma was more likely to occur to Black patients than to non-Black patients. More than a quarter (27%) of Black patients experienced violent trauma, compared to 11% of non-Black patients.

“It is very notable that among pregnant people who experience trauma, obstetric complications leading to preterm delivery were observed much more often for those who are Black,” Dr. Shah said. “A case series to understand the underlying causes could be very valuable.”

Black patients delivered an average 59 days (8 weeks, 3 days) after the trauma compared to an average 83 days (11 weeks, 6 days) for non-Black patients, but the difference was not statistically significant. However, preterm birth was more likely in non-Black patients (83%) than in Black patients (78%). A similar proportion of deliveries were preterm in Black (57%) and non-Black (56%) patients.

Though the poster did not show the data, the researchers wrote that Black women who experienced moderate to severe trauma after 24 weeks’ gestational age either had a preterm birth or a fetal demise.

Though the study findings warrant deeper investigation, the study has substantial limitations.

“It is challenging to generalize from this study because the sample size is small and it is from a single institution,” Dr. Shah said. “It does not appear to be adequately powered to draw statistically significant conclusions. In particular, the data are not adequate to support the authors’ statement that Black people are more likely to experience the forms of described trauma generally.”

The authors and Dr. Shah reported no disclosures.

Black patients experienced more moderate to severe violent trauma during pregnancy than did non-Black patients at a single Baltimore institution, according to a small retrospective cohort study presented in a poster at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

“Trauma is the leading nonobstetric cause of death in pregnant women,” and Black communities are at a disproportionately greater risk of trauma, Rebecca H. Jessel, MD, of Icahn School of Medicine at Mount Sinai in New York, and associates wrote in their poster.

The study’s findings raise research questions that need more exploration, according to Neel Shah, MD, assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, and founding director of the Delivery Decisions Initiative at Harvard’s Ariadne Labs.

“This is an interesting study that opens a line of inquiry into how trauma may impact the pregnancies of those who are Black differently,” Dr. Shah, who was not involved in the research, said in an interview. “The observed disparity is consistent with the racial inequities in outcomes we see across obstetric outcomes and requires further research into the causes and solutions.”

The researchers retrospectively reviewed all pregnant patients treated between 2015 and 2018 at the University of Maryland’s R Adams Cowley Shock Trauma Center in Baltimore. In addition to maternal demographics, details about the delivery, and perinatal outcomes, the researchers noted whether the trauma was violent, such as assault, or nonviolent, such as motor vehicle accidents. Moderate to severe trauma was defined as an injury severity score of at least 9.

Among 3,536 women aged 15-49 treated at the shock trauma center, 62 were pregnant, and 71% of these women were Black. Nineteen percent were White patients, 5% were Asian patients, and 5% were of a different race/ethnicity. Black patients were, on average, 27 years old at the time of the trauma. Non-Black patients were, on average, 25 years old. The average gestational age at the time of trauma was 25 weeks, 3 days in Black women and 23 weeks, 4 days in non-Black women.

The most common cause of trauma was a car accident, implicated in 56% of the trauma cases. Assault was the next most common cause of trauma, making up nearly a quarter (23%) of cases. The other injuries came from accidents (16%) or inhalation (5%). The average injury severity score was 4.7, with a mild injury for 76% of patients and a moderate to severe injury in 24%.

The researchers then compared the mechanisms and severity of injuries between Black and non-Black patients. The severity of trauma was similar between the two groups: Seventy-five percent of Black patients and 78% of non-Black patients had mild trauma with injury severity scores below 9. However, assault or another violent form of trauma was more likely to occur to Black patients than to non-Black patients. More than a quarter (27%) of Black patients experienced violent trauma, compared to 11% of non-Black patients.

“It is very notable that among pregnant people who experience trauma, obstetric complications leading to preterm delivery were observed much more often for those who are Black,” Dr. Shah said. “A case series to understand the underlying causes could be very valuable.”

Black patients delivered an average 59 days (8 weeks, 3 days) after the trauma compared to an average 83 days (11 weeks, 6 days) for non-Black patients, but the difference was not statistically significant. However, preterm birth was more likely in non-Black patients (83%) than in Black patients (78%). A similar proportion of deliveries were preterm in Black (57%) and non-Black (56%) patients.

Though the poster did not show the data, the researchers wrote that Black women who experienced moderate to severe trauma after 24 weeks’ gestational age either had a preterm birth or a fetal demise.

Though the study findings warrant deeper investigation, the study has substantial limitations.

“It is challenging to generalize from this study because the sample size is small and it is from a single institution,” Dr. Shah said. “It does not appear to be adequately powered to draw statistically significant conclusions. In particular, the data are not adequate to support the authors’ statement that Black people are more likely to experience the forms of described trauma generally.”

The authors and Dr. Shah reported no disclosures.

There has been a steady decline in the proportion of Black ob.gyn. residents from 2014 to 2019, according to new research published in JAMA Network Open.

Researchers found that Black residents made up 10.2% of ob.gyn. residents during the 2014-2015 academic year, compared with 7.9% in 2018-2019. Meanwhile, Native American or Alaskan Native and Native Hawaiian or Pacific Islander residents were the least represented in the field, making up just 0.2% of residents in 2014 and 0.1% in 2015.

“When we look at the trend [of Black residents] across several years, it’s surprising that not only is the proportion of [ob.gyn.] Black residents [decreasing], but it was going down at a faster rate than other specialties,” study author Claudia Lopez, MD, said in an interview.

The ob.gyn. specialty tends to have the highest proportion of underrepresented physicians, especially Black and Latino physicians, compared with other specialties, according to a 2016 study published in Obstetrics & Gynecology. This study also found that underrepresented minority ob.gyns. were more likely than White or Asian physicians to practice in underserved areas. However, researchers of the current study found that the decline in Black residents in this field is surprising.

“I do think that ob.gyn. is very unique in that it’s surgical but also has a lot of primary care elements,” Dr. Lopez said. “I think that’s probably why initially our specialty historically has more underrepresented minorities because it combines all those things and [physicians are] so intimate with their patient population.”

Dr. Lopez, resident physician at the University of California, Davis, and colleagues analyzed deidentified data on the race and ethnicity of more than 520,000 residents in ob.gyn., surgical, and nonsurgical specialties from JAMA Medical Education reports from 2014 to 2019.

They found that ob.gyn., surgical, and nonsurgical residents most commonly identified as White, followed by Asian. In addition to the decline in Black ob.gyn. residents, researchers noticed that the proportion of Latino residents remained relatively unchanged. Furthermore, while the racial and ethnic composition of residents varied each year, higher proportions of ob.gyn. residents identified as Black or Latino, compared with those in surgical and nonsurgical specialties. 

Researchers noted that, although their findings suggest ob.gyn. residencies have higher proportions of Black and Latino residents, compared with surgical and nonsurgical specialties, the diversity of the ob.gyn. programs lag behind the United States’ changing demographics.

“Medicine in general has a lot to do to match the [U.S. demographic] population,” Dr. Lopez said. “But at least the trend should hopefully be matching, showing some type of progression toward matching our population.”

Gnankang Sarah Napoe, MD, who was not involved in the study, said in an interview that she was saddened by the new findings and believes that if the decline in Black residents continues it would exacerbate racial disparities in obstetric and gynecological care.

“I think recruitment should focus more on specifically recruiting [underrepresented] populations of students into our field, because we know that they are a crucial part of narrowing the health disparities,” said Dr. Napoe, assistant professor* in the department of obstetrics and gynecology and reproductive sciences at the University of Pittsburgh.

Significant health disparities exist within women’s health and ob.gyn. care, with Black, American Indian, and Alaska Native women being two to three times more likely to have a pregnancy-related death than White women, according to the Centers for Disease Control and Prevention.

In an solicited commentary on the study, ob.gyns. from the University of Southern California, Los Angeles, referred to the declining population of Black ob.gyn. residents as “a failure of the medical education system to adapt to the changing demographic needs of its patients and cultivate diversity within the academic pipeline.”

One approach to addressing these health disparities is by increasing the diversity among health care practitioners. A 2020 study published in JAMA Network Open found that a shared identity between the physician and patient is linked to increased patient satisfaction and higher levels of trust.

“We know that, within ob.gyn., there are higher proportions of minority physicians, but just because we know that doesn’t mean that we’re doing everything right,” Dr. Lopez said. “When we look at the bigger picture,we’re not actually seeing the change we want to see. We need to not be complacent and keep evaluating ourselves, because I think that’s how you change.”

The authors and editorialists disclosed no relevant financial relationships.

*This article has been updated to reflect the correct title for Dr. Sarah Napoe.

There has been a steady decline in the proportion of Black ob.gyn. residents from 2014 to 2019, according to new research published in JAMA Network Open.

Researchers found that Black residents made up 10.2% of ob.gyn. residents during the 2014-2015 academic year, compared with 7.9% in 2018-2019. Meanwhile, Native American or Alaskan Native and Native Hawaiian or Pacific Islander residents were the least represented in the field, making up just 0.2% of residents in 2014 and 0.1% in 2015.

“When we look at the trend [of Black residents] across several years, it’s surprising that not only is the proportion of [ob.gyn.] Black residents [decreasing], but it was going down at a faster rate than other specialties,” study author Claudia Lopez, MD, said in an interview.

The ob.gyn. specialty tends to have the highest proportion of underrepresented physicians, especially Black and Latino physicians, compared with other specialties, according to a 2016 study published in Obstetrics & Gynecology. This study also found that underrepresented minority ob.gyns. were more likely than White or Asian physicians to practice in underserved areas. However, researchers of the current study found that the decline in Black residents in this field is surprising.

“I do think that ob.gyn. is very unique in that it’s surgical but also has a lot of primary care elements,” Dr. Lopez said. “I think that’s probably why initially our specialty historically has more underrepresented minorities because it combines all those things and [physicians are] so intimate with their patient population.”

Dr. Lopez, resident physician at the University of California, Davis, and colleagues analyzed deidentified data on the race and ethnicity of more than 520,000 residents in ob.gyn., surgical, and nonsurgical specialties from JAMA Medical Education reports from 2014 to 2019.

They found that ob.gyn., surgical, and nonsurgical residents most commonly identified as White, followed by Asian. In addition to the decline in Black ob.gyn. residents, researchers noticed that the proportion of Latino residents remained relatively unchanged. Furthermore, while the racial and ethnic composition of residents varied each year, higher proportions of ob.gyn. residents identified as Black or Latino, compared with those in surgical and nonsurgical specialties. 

Researchers noted that, although their findings suggest ob.gyn. residencies have higher proportions of Black and Latino residents, compared with surgical and nonsurgical specialties, the diversity of the ob.gyn. programs lag behind the United States’ changing demographics.

“Medicine in general has a lot to do to match the [U.S. demographic] population,” Dr. Lopez said. “But at least the trend should hopefully be matching, showing some type of progression toward matching our population.”

Gnankang Sarah Napoe, MD, who was not involved in the study, said in an interview that she was saddened by the new findings and believes that if the decline in Black residents continues it would exacerbate racial disparities in obstetric and gynecological care.

“I think recruitment should focus more on specifically recruiting [underrepresented] populations of students into our field, because we know that they are a crucial part of narrowing the health disparities,” said Dr. Napoe, assistant professor* in the department of obstetrics and gynecology and reproductive sciences at the University of Pittsburgh.

Significant health disparities exist within women’s health and ob.gyn. care, with Black, American Indian, and Alaska Native women being two to three times more likely to have a pregnancy-related death than White women, according to the Centers for Disease Control and Prevention.

In an solicited commentary on the study, ob.gyns. from the University of Southern California, Los Angeles, referred to the declining population of Black ob.gyn. residents as “a failure of the medical education system to adapt to the changing demographic needs of its patients and cultivate diversity within the academic pipeline.”

One approach to addressing these health disparities is by increasing the diversity among health care practitioners. A 2020 study published in JAMA Network Open found that a shared identity between the physician and patient is linked to increased patient satisfaction and higher levels of trust.

“We know that, within ob.gyn., there are higher proportions of minority physicians, but just because we know that doesn’t mean that we’re doing everything right,” Dr. Lopez said. “When we look at the bigger picture,we’re not actually seeing the change we want to see. We need to not be complacent and keep evaluating ourselves, because I think that’s how you change.”

The authors and editorialists disclosed no relevant financial relationships.

*This article has been updated to reflect the correct title for Dr. Sarah Napoe.

There has been a steady decline in the proportion of Black ob.gyn. residents from 2014 to 2019, according to new research published in JAMA Network Open.

Researchers found that Black residents made up 10.2% of ob.gyn. residents during the 2014-2015 academic year, compared with 7.9% in 2018-2019. Meanwhile, Native American or Alaskan Native and Native Hawaiian or Pacific Islander residents were the least represented in the field, making up just 0.2% of residents in 2014 and 0.1% in 2015.

“When we look at the trend [of Black residents] across several years, it’s surprising that not only is the proportion of [ob.gyn.] Black residents [decreasing], but it was going down at a faster rate than other specialties,” study author Claudia Lopez, MD, said in an interview.

The ob.gyn. specialty tends to have the highest proportion of underrepresented physicians, especially Black and Latino physicians, compared with other specialties, according to a 2016 study published in Obstetrics & Gynecology. This study also found that underrepresented minority ob.gyns. were more likely than White or Asian physicians to practice in underserved areas. However, researchers of the current study found that the decline in Black residents in this field is surprising.

“I do think that ob.gyn. is very unique in that it’s surgical but also has a lot of primary care elements,” Dr. Lopez said. “I think that’s probably why initially our specialty historically has more underrepresented minorities because it combines all those things and [physicians are] so intimate with their patient population.”

Dr. Lopez, resident physician at the University of California, Davis, and colleagues analyzed deidentified data on the race and ethnicity of more than 520,000 residents in ob.gyn., surgical, and nonsurgical specialties from JAMA Medical Education reports from 2014 to 2019.

They found that ob.gyn., surgical, and nonsurgical residents most commonly identified as White, followed by Asian. In addition to the decline in Black ob.gyn. residents, researchers noticed that the proportion of Latino residents remained relatively unchanged. Furthermore, while the racial and ethnic composition of residents varied each year, higher proportions of ob.gyn. residents identified as Black or Latino, compared with those in surgical and nonsurgical specialties. 

Researchers noted that, although their findings suggest ob.gyn. residencies have higher proportions of Black and Latino residents, compared with surgical and nonsurgical specialties, the diversity of the ob.gyn. programs lag behind the United States’ changing demographics.

“Medicine in general has a lot to do to match the [U.S. demographic] population,” Dr. Lopez said. “But at least the trend should hopefully be matching, showing some type of progression toward matching our population.”

Gnankang Sarah Napoe, MD, who was not involved in the study, said in an interview that she was saddened by the new findings and believes that if the decline in Black residents continues it would exacerbate racial disparities in obstetric and gynecological care.

“I think recruitment should focus more on specifically recruiting [underrepresented] populations of students into our field, because we know that they are a crucial part of narrowing the health disparities,” said Dr. Napoe, assistant professor* in the department of obstetrics and gynecology and reproductive sciences at the University of Pittsburgh.

Significant health disparities exist within women’s health and ob.gyn. care, with Black, American Indian, and Alaska Native women being two to three times more likely to have a pregnancy-related death than White women, according to the Centers for Disease Control and Prevention.

In an solicited commentary on the study, ob.gyns. from the University of Southern California, Los Angeles, referred to the declining population of Black ob.gyn. residents as “a failure of the medical education system to adapt to the changing demographic needs of its patients and cultivate diversity within the academic pipeline.”

One approach to addressing these health disparities is by increasing the diversity among health care practitioners. A 2020 study published in JAMA Network Open found that a shared identity between the physician and patient is linked to increased patient satisfaction and higher levels of trust.

“We know that, within ob.gyn., there are higher proportions of minority physicians, but just because we know that doesn’t mean that we’re doing everything right,” Dr. Lopez said. “When we look at the bigger picture,we’re not actually seeing the change we want to see. We need to not be complacent and keep evaluating ourselves, because I think that’s how you change.”

The authors and editorialists disclosed no relevant financial relationships.

*This article has been updated to reflect the correct title for Dr. Sarah Napoe.