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Sharon Worcester is an award-winning medical journalist for MDedge News. She has been with the company since 1996, first as the Southeast Bureau Chief (1996-2009) when the company was known as International Medical News Group, then as a freelance writer (2010-2015) before returning as a reporter in 2015. She previously worked as a daily newspaper reporter covering health and local government. Sharon currently reports primarily on oncology and hematology. She has a BA from Eckerd College and an MA in Mass Communication/Print Journalism from the University of Florida. Connect with her via LinkedIn and follow her on twitter @SW_MedReporter.
IL-6, CRP are prognostic for checkpoint inhibition in melanoma
CHICAGO – according to post hoc analyses of data from three randomized CheckMate studies.
In 70 treatment-naive patients from the randomized phase 2 CheckMate 064 study who received sequential treatment with the programmed death-1 (PD-1) checkpoint inhibitor nivolumab (NIVO) followed by the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) checkpoint inhibitor ipilimumab (IPI), best overall response was modestly associated with lower baseline serum IL-6 (P = .087) and significantly associated with on-treatment IL-6 (P = .006). In 70 patients who received IPI then NIVO, best overall response was associated only with on-treatment IL-6 (P = .043), Jeffrey S. Weber, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
“This stimulated us to look at associations with survival ... and there apparently was a significant association with high IL-6 levels in the serum both pretreatment and on treatment in both arms, whether they got NIVO then IPI followed by NIVO maintenance, or IPI then NIVO, also followed by NIVO maintenance,” he said.
After adjusting for covariates, the hazard ratios for survival for baseline IL-6 below versus above the median were 7.81 and 1.07, in the groups, respectively. No deaths occurred in the NIVO-IPI group (thus, no HR), but the HR for survival based on on-treatment IL-6 below versus above the median in the IPI-NIVO group was 1.92.
“So initial conclusions: High baseline and on-treatment IL-6 levels in the serum were associated with poor survival,” said Dr. Weber, deputy director of the Perlmutter Cancer Center, New York University Langone Medical Center.
This finding prompted evaluation of additional samples from the randomized CheckMate 066 study, which compared dacarbazine chemotherapy (the standard of care at the time) and NIVO in 400 treatment-naive patients with BRAF wild-type disease.
Again, baseline IL-6 levels (nondetectable vs. detectable) were associated with better overall survival (OS) in both groups (adjusted HRs, 1.79 and 1.54).
“So this is not a predictive marker, this is a baseline prognostic marker,” he said.
In the international, three-arm, randomized phase 3 CheckMate 067 study, which compared IPI, NIVO, and IPI+NIVO in 945 treatment-naive patients with either BRAF wild-type or BRAF mutated disease, baseline IL-6 levels (nondetectable vs. detectable) again were associated with better OS in all 3 arms (adjusted HRs, 3.13 for NIVO, 2.67 for NIVO+IPI, and 4.06 for IPI alone).
A multivariate analysis of data from the CheckMate 066 and 067 studies, with controlling for lactic acid deydrogenase, performance status, and disease stage, provided additional “impressive evidence” of IL-6 as a potent prognostic factor, Dr. Weber said.
“We then looked at CRP. I’ve always been interested in CRP because in a recent publication CRP was found to be associated with outcomes in patients who got PD-1, and the higher the CRP, the worse they did,” he said.
In CheckMate 064 there was modest association between lower baseline CRP and best overall response in both the NIVO-IPI and IPI-NIVO groups (P = .069 and 0.009, respectively), and on treatment, the association was really only seen in the IPI-NIVO group (P = .210 for NIVO-IPI and 0.015 for IPI-NIVO), in which the higher CRP levels were associated with progression or stability.
For survival, however, both baseline and on-treatment CRP levels were associated with OS; baseline serum CRP above the median was associated with shorter OS (HRs, 7.25 for NIVO-IPI and 1.53 for IPI-NIVO), and a similar trend was seen for on-treatment CRP (HRs, 1.60 and 2.0, respectively).
In CheckMate 066, the association between CRP and OS was also apparent, but not as impressive for NIVO alone (HR, 0.996) as it was for dacarbazine (HR, 1.90), and similar to CheckMate 064, higher baseline CRP levels were associated with shorter survival and were prognostic, he said.
In CheckMate 067, similar trends were seen across the treatment arms, and they were similar to those seen for IL-6, with higher baseline CRP levels (at or above median versus below) associated with shorter OS (HRs, 1.46 for NIVO, 1.26 for NIVO+IPI, and 1.48 for IPI alone).
To better understand how CRP might inhibit the effects of PD-1 and how it could have an immune effect – as also indicated by some prior data – Dr. Weber and colleagues conducted additional in vitro studies to examine the impact of exogenous CRP on T-cell function; they found that CRP affected the earliest steps in T-cell signaling and activation, thereby dampening antitumor immune responses.
Acute phase reactants such as CRP and chronic inflammatory proteins including IL-6 (which induces production of CRP from the liver) have been associated with poor prognosis in a variety of cancers, as well as with poor outcomes after anti–PD-1 or programmed death-ligand 1 (PD-L1) therapy in melanoma and other cancers, Dr. Weber said.
“In murine models of melanoma and pancreatic cancer, combined treatment with anti-IL-6 blockade and anti–PD-1/PD-L1 antibodies enhances antitumor immune responses and efficacy,” he explained, noting that the current analyses were undertaken based on those findings and on “a significant body of data” from other groups and from his own lab.
The current findings suggest that IL-6 and CRP may be prognostic for immune checkpoint inhibitor therapies in patients with melanoma, he said, adding that “blockade of IL-6 and CRP synthesis and/or activity in combination with immune checkpoint therapies may enhance responses and survival rates in patients with different cancers, including melanomas.”
To that end, an investigator-sponsored trial looking at IPI-NIVO with the IL-6–blocking antibody tocilizumab has been approved and will start accruing patients in the next few months, he said.
During a discussion of the findings at the meeting, Charles G. Drake, MD, PhD, associate director for clinical research at the Herbert Irving Comprehensive Cancer Center at Columbia University, New York, said that “Dr. Weber and his colleagues should be commended for really trying to show what CRP does to T-cell activation, and in the studies he showed us, it’s clearly negative.”
“But IL-6 is a pleiotropic cytokine. It will be very interesting to see what happens in the prospective clinical trial that he mentioned, in terms of all the other effects on CD-4 cells, neutrophils, and macrophages,” said Dr. Drake, who also is codirector of Columbia’s Cancer Immunotherapy Program. “Nevertheless, I think the data were clear that IL-6 and CRP are negative prognostic biomarkers in melanoma.”
Of note, the development of a biomarker identified in a trial typically takes many steps, but in the case of IL-6 – and perhaps even more so for CRP – the pathway is relatively short, Dr. Drake said.
“That’s because CRP is a validated and [Food and Drug Administration]–approved test; you can order it to assess cardiovascular risk in almost any hospital in the United States, and so the analyte – this part of the qualification – is done,” he explained. “I think if this was validated prospectively we could have CRP as a negative prognostic – not predictive – biomarker in melanoma, actually.”
Dr. Weber and Dr. Drake each reported relationships with numerous companies, including stock and other ownership interests and patents, consulting or advisory roles and/or receipt of honoraria, research funding to their respective institutions, and payment for travel, accommodations, and expenses
SOURCE: Weber J et al. ASCO 2019, Abstract 100.
CHICAGO – according to post hoc analyses of data from three randomized CheckMate studies.
In 70 treatment-naive patients from the randomized phase 2 CheckMate 064 study who received sequential treatment with the programmed death-1 (PD-1) checkpoint inhibitor nivolumab (NIVO) followed by the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) checkpoint inhibitor ipilimumab (IPI), best overall response was modestly associated with lower baseline serum IL-6 (P = .087) and significantly associated with on-treatment IL-6 (P = .006). In 70 patients who received IPI then NIVO, best overall response was associated only with on-treatment IL-6 (P = .043), Jeffrey S. Weber, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
“This stimulated us to look at associations with survival ... and there apparently was a significant association with high IL-6 levels in the serum both pretreatment and on treatment in both arms, whether they got NIVO then IPI followed by NIVO maintenance, or IPI then NIVO, also followed by NIVO maintenance,” he said.
After adjusting for covariates, the hazard ratios for survival for baseline IL-6 below versus above the median were 7.81 and 1.07, in the groups, respectively. No deaths occurred in the NIVO-IPI group (thus, no HR), but the HR for survival based on on-treatment IL-6 below versus above the median in the IPI-NIVO group was 1.92.
“So initial conclusions: High baseline and on-treatment IL-6 levels in the serum were associated with poor survival,” said Dr. Weber, deputy director of the Perlmutter Cancer Center, New York University Langone Medical Center.
This finding prompted evaluation of additional samples from the randomized CheckMate 066 study, which compared dacarbazine chemotherapy (the standard of care at the time) and NIVO in 400 treatment-naive patients with BRAF wild-type disease.
Again, baseline IL-6 levels (nondetectable vs. detectable) were associated with better overall survival (OS) in both groups (adjusted HRs, 1.79 and 1.54).
“So this is not a predictive marker, this is a baseline prognostic marker,” he said.
In the international, three-arm, randomized phase 3 CheckMate 067 study, which compared IPI, NIVO, and IPI+NIVO in 945 treatment-naive patients with either BRAF wild-type or BRAF mutated disease, baseline IL-6 levels (nondetectable vs. detectable) again were associated with better OS in all 3 arms (adjusted HRs, 3.13 for NIVO, 2.67 for NIVO+IPI, and 4.06 for IPI alone).
A multivariate analysis of data from the CheckMate 066 and 067 studies, with controlling for lactic acid deydrogenase, performance status, and disease stage, provided additional “impressive evidence” of IL-6 as a potent prognostic factor, Dr. Weber said.
“We then looked at CRP. I’ve always been interested in CRP because in a recent publication CRP was found to be associated with outcomes in patients who got PD-1, and the higher the CRP, the worse they did,” he said.
In CheckMate 064 there was modest association between lower baseline CRP and best overall response in both the NIVO-IPI and IPI-NIVO groups (P = .069 and 0.009, respectively), and on treatment, the association was really only seen in the IPI-NIVO group (P = .210 for NIVO-IPI and 0.015 for IPI-NIVO), in which the higher CRP levels were associated with progression or stability.
For survival, however, both baseline and on-treatment CRP levels were associated with OS; baseline serum CRP above the median was associated with shorter OS (HRs, 7.25 for NIVO-IPI and 1.53 for IPI-NIVO), and a similar trend was seen for on-treatment CRP (HRs, 1.60 and 2.0, respectively).
In CheckMate 066, the association between CRP and OS was also apparent, but not as impressive for NIVO alone (HR, 0.996) as it was for dacarbazine (HR, 1.90), and similar to CheckMate 064, higher baseline CRP levels were associated with shorter survival and were prognostic, he said.
In CheckMate 067, similar trends were seen across the treatment arms, and they were similar to those seen for IL-6, with higher baseline CRP levels (at or above median versus below) associated with shorter OS (HRs, 1.46 for NIVO, 1.26 for NIVO+IPI, and 1.48 for IPI alone).
To better understand how CRP might inhibit the effects of PD-1 and how it could have an immune effect – as also indicated by some prior data – Dr. Weber and colleagues conducted additional in vitro studies to examine the impact of exogenous CRP on T-cell function; they found that CRP affected the earliest steps in T-cell signaling and activation, thereby dampening antitumor immune responses.
Acute phase reactants such as CRP and chronic inflammatory proteins including IL-6 (which induces production of CRP from the liver) have been associated with poor prognosis in a variety of cancers, as well as with poor outcomes after anti–PD-1 or programmed death-ligand 1 (PD-L1) therapy in melanoma and other cancers, Dr. Weber said.
“In murine models of melanoma and pancreatic cancer, combined treatment with anti-IL-6 blockade and anti–PD-1/PD-L1 antibodies enhances antitumor immune responses and efficacy,” he explained, noting that the current analyses were undertaken based on those findings and on “a significant body of data” from other groups and from his own lab.
The current findings suggest that IL-6 and CRP may be prognostic for immune checkpoint inhibitor therapies in patients with melanoma, he said, adding that “blockade of IL-6 and CRP synthesis and/or activity in combination with immune checkpoint therapies may enhance responses and survival rates in patients with different cancers, including melanomas.”
To that end, an investigator-sponsored trial looking at IPI-NIVO with the IL-6–blocking antibody tocilizumab has been approved and will start accruing patients in the next few months, he said.
During a discussion of the findings at the meeting, Charles G. Drake, MD, PhD, associate director for clinical research at the Herbert Irving Comprehensive Cancer Center at Columbia University, New York, said that “Dr. Weber and his colleagues should be commended for really trying to show what CRP does to T-cell activation, and in the studies he showed us, it’s clearly negative.”
“But IL-6 is a pleiotropic cytokine. It will be very interesting to see what happens in the prospective clinical trial that he mentioned, in terms of all the other effects on CD-4 cells, neutrophils, and macrophages,” said Dr. Drake, who also is codirector of Columbia’s Cancer Immunotherapy Program. “Nevertheless, I think the data were clear that IL-6 and CRP are negative prognostic biomarkers in melanoma.”
Of note, the development of a biomarker identified in a trial typically takes many steps, but in the case of IL-6 – and perhaps even more so for CRP – the pathway is relatively short, Dr. Drake said.
“That’s because CRP is a validated and [Food and Drug Administration]–approved test; you can order it to assess cardiovascular risk in almost any hospital in the United States, and so the analyte – this part of the qualification – is done,” he explained. “I think if this was validated prospectively we could have CRP as a negative prognostic – not predictive – biomarker in melanoma, actually.”
Dr. Weber and Dr. Drake each reported relationships with numerous companies, including stock and other ownership interests and patents, consulting or advisory roles and/or receipt of honoraria, research funding to their respective institutions, and payment for travel, accommodations, and expenses
SOURCE: Weber J et al. ASCO 2019, Abstract 100.
CHICAGO – according to post hoc analyses of data from three randomized CheckMate studies.
In 70 treatment-naive patients from the randomized phase 2 CheckMate 064 study who received sequential treatment with the programmed death-1 (PD-1) checkpoint inhibitor nivolumab (NIVO) followed by the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) checkpoint inhibitor ipilimumab (IPI), best overall response was modestly associated with lower baseline serum IL-6 (P = .087) and significantly associated with on-treatment IL-6 (P = .006). In 70 patients who received IPI then NIVO, best overall response was associated only with on-treatment IL-6 (P = .043), Jeffrey S. Weber, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
“This stimulated us to look at associations with survival ... and there apparently was a significant association with high IL-6 levels in the serum both pretreatment and on treatment in both arms, whether they got NIVO then IPI followed by NIVO maintenance, or IPI then NIVO, also followed by NIVO maintenance,” he said.
After adjusting for covariates, the hazard ratios for survival for baseline IL-6 below versus above the median were 7.81 and 1.07, in the groups, respectively. No deaths occurred in the NIVO-IPI group (thus, no HR), but the HR for survival based on on-treatment IL-6 below versus above the median in the IPI-NIVO group was 1.92.
“So initial conclusions: High baseline and on-treatment IL-6 levels in the serum were associated with poor survival,” said Dr. Weber, deputy director of the Perlmutter Cancer Center, New York University Langone Medical Center.
This finding prompted evaluation of additional samples from the randomized CheckMate 066 study, which compared dacarbazine chemotherapy (the standard of care at the time) and NIVO in 400 treatment-naive patients with BRAF wild-type disease.
Again, baseline IL-6 levels (nondetectable vs. detectable) were associated with better overall survival (OS) in both groups (adjusted HRs, 1.79 and 1.54).
“So this is not a predictive marker, this is a baseline prognostic marker,” he said.
In the international, three-arm, randomized phase 3 CheckMate 067 study, which compared IPI, NIVO, and IPI+NIVO in 945 treatment-naive patients with either BRAF wild-type or BRAF mutated disease, baseline IL-6 levels (nondetectable vs. detectable) again were associated with better OS in all 3 arms (adjusted HRs, 3.13 for NIVO, 2.67 for NIVO+IPI, and 4.06 for IPI alone).
A multivariate analysis of data from the CheckMate 066 and 067 studies, with controlling for lactic acid deydrogenase, performance status, and disease stage, provided additional “impressive evidence” of IL-6 as a potent prognostic factor, Dr. Weber said.
“We then looked at CRP. I’ve always been interested in CRP because in a recent publication CRP was found to be associated with outcomes in patients who got PD-1, and the higher the CRP, the worse they did,” he said.
In CheckMate 064 there was modest association between lower baseline CRP and best overall response in both the NIVO-IPI and IPI-NIVO groups (P = .069 and 0.009, respectively), and on treatment, the association was really only seen in the IPI-NIVO group (P = .210 for NIVO-IPI and 0.015 for IPI-NIVO), in which the higher CRP levels were associated with progression or stability.
For survival, however, both baseline and on-treatment CRP levels were associated with OS; baseline serum CRP above the median was associated with shorter OS (HRs, 7.25 for NIVO-IPI and 1.53 for IPI-NIVO), and a similar trend was seen for on-treatment CRP (HRs, 1.60 and 2.0, respectively).
In CheckMate 066, the association between CRP and OS was also apparent, but not as impressive for NIVO alone (HR, 0.996) as it was for dacarbazine (HR, 1.90), and similar to CheckMate 064, higher baseline CRP levels were associated with shorter survival and were prognostic, he said.
In CheckMate 067, similar trends were seen across the treatment arms, and they were similar to those seen for IL-6, with higher baseline CRP levels (at or above median versus below) associated with shorter OS (HRs, 1.46 for NIVO, 1.26 for NIVO+IPI, and 1.48 for IPI alone).
To better understand how CRP might inhibit the effects of PD-1 and how it could have an immune effect – as also indicated by some prior data – Dr. Weber and colleagues conducted additional in vitro studies to examine the impact of exogenous CRP on T-cell function; they found that CRP affected the earliest steps in T-cell signaling and activation, thereby dampening antitumor immune responses.
Acute phase reactants such as CRP and chronic inflammatory proteins including IL-6 (which induces production of CRP from the liver) have been associated with poor prognosis in a variety of cancers, as well as with poor outcomes after anti–PD-1 or programmed death-ligand 1 (PD-L1) therapy in melanoma and other cancers, Dr. Weber said.
“In murine models of melanoma and pancreatic cancer, combined treatment with anti-IL-6 blockade and anti–PD-1/PD-L1 antibodies enhances antitumor immune responses and efficacy,” he explained, noting that the current analyses were undertaken based on those findings and on “a significant body of data” from other groups and from his own lab.
The current findings suggest that IL-6 and CRP may be prognostic for immune checkpoint inhibitor therapies in patients with melanoma, he said, adding that “blockade of IL-6 and CRP synthesis and/or activity in combination with immune checkpoint therapies may enhance responses and survival rates in patients with different cancers, including melanomas.”
To that end, an investigator-sponsored trial looking at IPI-NIVO with the IL-6–blocking antibody tocilizumab has been approved and will start accruing patients in the next few months, he said.
During a discussion of the findings at the meeting, Charles G. Drake, MD, PhD, associate director for clinical research at the Herbert Irving Comprehensive Cancer Center at Columbia University, New York, said that “Dr. Weber and his colleagues should be commended for really trying to show what CRP does to T-cell activation, and in the studies he showed us, it’s clearly negative.”
“But IL-6 is a pleiotropic cytokine. It will be very interesting to see what happens in the prospective clinical trial that he mentioned, in terms of all the other effects on CD-4 cells, neutrophils, and macrophages,” said Dr. Drake, who also is codirector of Columbia’s Cancer Immunotherapy Program. “Nevertheless, I think the data were clear that IL-6 and CRP are negative prognostic biomarkers in melanoma.”
Of note, the development of a biomarker identified in a trial typically takes many steps, but in the case of IL-6 – and perhaps even more so for CRP – the pathway is relatively short, Dr. Drake said.
“That’s because CRP is a validated and [Food and Drug Administration]–approved test; you can order it to assess cardiovascular risk in almost any hospital in the United States, and so the analyte – this part of the qualification – is done,” he explained. “I think if this was validated prospectively we could have CRP as a negative prognostic – not predictive – biomarker in melanoma, actually.”
Dr. Weber and Dr. Drake each reported relationships with numerous companies, including stock and other ownership interests and patents, consulting or advisory roles and/or receipt of honoraria, research funding to their respective institutions, and payment for travel, accommodations, and expenses
SOURCE: Weber J et al. ASCO 2019, Abstract 100.
REPORTING FROM ASCO 2019
Ovarian cancer diagnosed and treated earlier under ACA
CHICAGO – , according to a comparison of National Cancer Database surveys from 2006-2009 and 2011-2014.
During the post-Affordable Care Act (ACA) years of 2011-2014, compared with the pre-ACA years of 2004-2009, a treatment group of women aged 21-64 years with ovarian cancer was more likely to be diagnosed at an early stage, compared with a control group of women aged 65 years and older (difference-in-differences [DD]=1.7%), Anna Jo Smith, MD, reported at the annual meeting of the American Society of Clinical Oncology.
Also, the ACA was associated with more women aged 21-64 receiving treatment within 30 days of diagnosis (DD = 1.6%), said Dr. Smith, a 4th-year resident at Johns Hopkins University, Baltimore.
Among women with public insurance, the ACA was associated with even greater improvement in early-stage diagnosis and treatment within 30 days in the treatment group vs. the controls (DD = 2.5% for each), she said, noting that the improvements were seen across race, income, and education groups.
The findings are based on pre-ACA surveys from 35,842 women aged 21-64 years and 28,895 women aged 65 years, and from post-ACA surveys from 37,145 women and 30,604 women in those age groups, respectively, and were adjusted for patient race, living in a rural area, area-level household income and education level, Charlson comorbidity score, distance traveled for care, Census region, and care at an academic center.
The 2010 ACA expanded access to insurance and care for many Americans, and the objective of this study was to evaluate the impact of that access on women with ovarian cancer, Dr. Smith explained.
“Under the 2010 Affordable Care Act, women with ovarian cancer were more likely to be diagnosed at an early stage and receive treatment within 30 days of diagnosis,” she said. “As stage and treatment are the major determinants of survival advantage, these gains under the ACA may have long-term impacts on the survival, health, and well-being of women with ovarian cancer.”
Dr. Smith reported having no disclosures.
SOURCE: Smith A et al., ASCO 2019. Abstract LBA5563.
CHICAGO – , according to a comparison of National Cancer Database surveys from 2006-2009 and 2011-2014.
During the post-Affordable Care Act (ACA) years of 2011-2014, compared with the pre-ACA years of 2004-2009, a treatment group of women aged 21-64 years with ovarian cancer was more likely to be diagnosed at an early stage, compared with a control group of women aged 65 years and older (difference-in-differences [DD]=1.7%), Anna Jo Smith, MD, reported at the annual meeting of the American Society of Clinical Oncology.
Also, the ACA was associated with more women aged 21-64 receiving treatment within 30 days of diagnosis (DD = 1.6%), said Dr. Smith, a 4th-year resident at Johns Hopkins University, Baltimore.
Among women with public insurance, the ACA was associated with even greater improvement in early-stage diagnosis and treatment within 30 days in the treatment group vs. the controls (DD = 2.5% for each), she said, noting that the improvements were seen across race, income, and education groups.
The findings are based on pre-ACA surveys from 35,842 women aged 21-64 years and 28,895 women aged 65 years, and from post-ACA surveys from 37,145 women and 30,604 women in those age groups, respectively, and were adjusted for patient race, living in a rural area, area-level household income and education level, Charlson comorbidity score, distance traveled for care, Census region, and care at an academic center.
The 2010 ACA expanded access to insurance and care for many Americans, and the objective of this study was to evaluate the impact of that access on women with ovarian cancer, Dr. Smith explained.
“Under the 2010 Affordable Care Act, women with ovarian cancer were more likely to be diagnosed at an early stage and receive treatment within 30 days of diagnosis,” she said. “As stage and treatment are the major determinants of survival advantage, these gains under the ACA may have long-term impacts on the survival, health, and well-being of women with ovarian cancer.”
Dr. Smith reported having no disclosures.
SOURCE: Smith A et al., ASCO 2019. Abstract LBA5563.
CHICAGO – , according to a comparison of National Cancer Database surveys from 2006-2009 and 2011-2014.
During the post-Affordable Care Act (ACA) years of 2011-2014, compared with the pre-ACA years of 2004-2009, a treatment group of women aged 21-64 years with ovarian cancer was more likely to be diagnosed at an early stage, compared with a control group of women aged 65 years and older (difference-in-differences [DD]=1.7%), Anna Jo Smith, MD, reported at the annual meeting of the American Society of Clinical Oncology.
Also, the ACA was associated with more women aged 21-64 receiving treatment within 30 days of diagnosis (DD = 1.6%), said Dr. Smith, a 4th-year resident at Johns Hopkins University, Baltimore.
Among women with public insurance, the ACA was associated with even greater improvement in early-stage diagnosis and treatment within 30 days in the treatment group vs. the controls (DD = 2.5% for each), she said, noting that the improvements were seen across race, income, and education groups.
The findings are based on pre-ACA surveys from 35,842 women aged 21-64 years and 28,895 women aged 65 years, and from post-ACA surveys from 37,145 women and 30,604 women in those age groups, respectively, and were adjusted for patient race, living in a rural area, area-level household income and education level, Charlson comorbidity score, distance traveled for care, Census region, and care at an academic center.
The 2010 ACA expanded access to insurance and care for many Americans, and the objective of this study was to evaluate the impact of that access on women with ovarian cancer, Dr. Smith explained.
“Under the 2010 Affordable Care Act, women with ovarian cancer were more likely to be diagnosed at an early stage and receive treatment within 30 days of diagnosis,” she said. “As stage and treatment are the major determinants of survival advantage, these gains under the ACA may have long-term impacts on the survival, health, and well-being of women with ovarian cancer.”
Dr. Smith reported having no disclosures.
SOURCE: Smith A et al., ASCO 2019. Abstract LBA5563.
REPORTING FROM ASCO 2019
Abnormal uterine bleeding: When can you forgo biopsy?
NASHVILLE, TENN. – Ultrasound is a reasonable first step for the evaluation of postmenopausal women with abnormal uterine bleeding and endometrial thickness up to 5 mm, according to James Shwayder, MD, JD.
About a third of such patients presenting with abnormal uterine bleeding (AUB) will have an endometrial polyp or submucous myoma, Dr. Shwayder explained during a presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
However, recurrent bleeding warrants further work-up, he said.
The 5-mm value is based on a number of studies, which, in sum, show that the negative predictive value for cancer for endometrial thickness less than 4 mm is greater than 99%, said Dr. Shwayder, chief of the division of gynecology and director of the fellowship in advanced endoscopy obstetrics, gynecology, and women’s health at the University of Louisville (Ky.).
“In fact ... the risk of cancer is 1 in 917,” he added. “That’s pretty good ... that’s a great screening tool.”
The question is whether one can feel comfortable foregoing biopsy in such cases, he said, describing a 61-year-old patient with a 3.9-mm endometrium and AUB for 3 days, 3 weeks prior to her visit.
There are two possibilities: The patient will either have no further bleeding, or she will continue to bleed, he said, noting that a 2003 Swedish study provides some guidance in the case of continued bleeding (Am J Obstet Gynecol. 2003;188:401-8).
The investigators initially looked at histology associated with endometrial thickness in 394 postmenopausal women referred for AUB between 1987 and 1990. Both transvaginal ultrasound and dilatation and curettage were performed, and the findings were correlated.
“But they had the rare opportunity to take patients who had benign evaluations and bring them back 10 years later,” Dr. Shwayder said. “What they found was that, regardless of the endometrial thickness, if it was benign initially and they did not bleed over that 10-year period, no one had cancer.”
However, among the patients followed for 10 years who had recurrent bleeding, 10% had cancer and 12% had hyperplasia. Thus, deciding against a biopsy in this case is supported by good data; if the patient doesn’t bleed, she has an “incredibly low risk of cancer,” he said.
“If they bleed again, you’ve gotta work ‘em up,” he stressed. “Don’t continue to say, ‘Well, let me repeat the ultrasound and see if it’s thinner or thicker.’ No. They need to be evaluated.”
Keep in mind that if a biopsy is performed as the first step, the chances of the results coming back as tissue insufficient for diagnosis (TIFD) are increased, and a repeat biopsy will be necessary because of the inconclusive findings, Dr. Shwayder said. It helps to warn a patient in advance that their thin endometrium makes it highly likely that a repeat biopsy will be necessary, as 90% come back as TIFD or atrophy.
Importantly, though, ACOG says endometrial sampling should be performed first line in patients over age 45 years with AUB.
“I’ll be honest – I use ultrasound in these patients because of the fact that a third will have some sort of structural defect, and the focal abnormalities are things we’re not going to be able to pick up with a straight biopsy, but we have to be cognizant that the college recommends biopsy in this population,” Dr. Shwayder said.
Asymptomatic endometrial thickening
Postmenopausal women are increasingly being referred for asymptomatic endometrial thickening that is found incidentally during an unrelated evaluation, Dr. Shwayder said, noting that evidence to date on how to approach such cases is conflicting.
Although ACOG is working on a recommendation, none is currently available, he said.
However, a 2001 study comparing 123 asymptomatic patients with 90 symptomatic patients, all with an endometrial thickness of greater than 10 mm, found no prognostic advantage to screening versus waiting until bleeding occurred, he noted (Euro J Cancer. 2001;37:64-71).
Overall, 13% of the patients had cancer, 50% had polyps, and 17% had hyperplasia.
“But what they emphasized was ... the length [of time] the patients complained of abnormal uterine bleeding. If it was less than 8 weeks ... there was no statistical difference in outcome, but if it was over 8 weeks there was a statistically significant difference in the grade of disease – a prognostic advantage for those patients who were screened versus symptomatic.”
The overall 5-year disease-free survival was 86% for asymptomatic versus 77% for symptomatic patients; for those with bleeding for less than 8 weeks, it was 98% versus 83%, respectively. The differences were not statistically different. However, for those with bleeding for 8-16 weeks it was 90% versus 74%, and for those with bleeding for more than 16 weeks it was 69% versus 62%, respectively, and those differences were statistically significant.
The problem is that many patients put off coming in for a long time, which means they are in a category with a worse prognosis when they do come in, Dr. Shwayder said. That’s not to say everyone should be screened, but there is no prognostic advantage to screening asymptomatic patients versus symptomatic patients who had bleeding for less than 8 weeks.
“It’s a little clarification, but I think an important one,” he noted.
Another study of 1,607 patients with endometrial thickening, including 233 who were asymptomatic and 1,374 who were symptomatic, found a lower rate of deep invasion with stage 1 disease, but no difference in the rate of more advanced disease, and no association with a more favorable outcome between the groups. (Am J Obstet Gynecol. 2018;219[2]:183e1-6).
Additionally, a study of 42 asymptomatic patients, 95 symptomatic patients with bleeding for less than 3 months, and 83 symptomatic patients with bleeding for more than 3 months showed a nonsignificant trend toward poorer 5-year survival in patients with a longer history of bleeding prior to surgery (Arch Gynecol Obstet 2013;288:1361-4).
“So now the question becomes how thick is too thick [and whether there is] some threshold where we ought to be evaluating patients and some threshold where we’re not,” he said.
The risk of malignancy among symptomatic postmenopausal women with an endometrial thickness greater than 5 mm is 7.3%, and the risk is similar at 6.7% in asymptomatic patients with an endometrial thickness of 11 mm or greater, according to a 2004 study by Smith-Bindman et al. (Ultrasound Obstet Gynecol. 2004;24:558-65).
“So the thought process here is that if a patient is asymptomatic, but the endometrium is over 11 mm, maybe we ought to evaluate that patient, because her risk of cancer is equivalent to that of someone who presents with postmenopausal bleeding and has an endometrium greater than 5 mm,” he explained.
In fact, a practice guideline from the Society of Obstetricians and Gynecologists of Canada recommends that women with endometrial thickness over 11 mm and other risk factors for cancer – such as obesity, hypertension, or late menopause – should be referred to a gynecologist for investigation, Dr. Shwayder said, adding that he also considers increased vascularity, heterogeneity in the endometrium, and fluid seen on a scan as cause for further evaluation.
“But endometrial sampling without bleeding should not be routinely performed,” he said. “So don’t routinely [sample] but based on risk factors and ultrasound findings, you may want to consider evaluating these patients further.”
Dr. Shwayder is a consultant for GE Ultrasound.
NASHVILLE, TENN. – Ultrasound is a reasonable first step for the evaluation of postmenopausal women with abnormal uterine bleeding and endometrial thickness up to 5 mm, according to James Shwayder, MD, JD.
About a third of such patients presenting with abnormal uterine bleeding (AUB) will have an endometrial polyp or submucous myoma, Dr. Shwayder explained during a presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
However, recurrent bleeding warrants further work-up, he said.
The 5-mm value is based on a number of studies, which, in sum, show that the negative predictive value for cancer for endometrial thickness less than 4 mm is greater than 99%, said Dr. Shwayder, chief of the division of gynecology and director of the fellowship in advanced endoscopy obstetrics, gynecology, and women’s health at the University of Louisville (Ky.).
“In fact ... the risk of cancer is 1 in 917,” he added. “That’s pretty good ... that’s a great screening tool.”
The question is whether one can feel comfortable foregoing biopsy in such cases, he said, describing a 61-year-old patient with a 3.9-mm endometrium and AUB for 3 days, 3 weeks prior to her visit.
There are two possibilities: The patient will either have no further bleeding, or she will continue to bleed, he said, noting that a 2003 Swedish study provides some guidance in the case of continued bleeding (Am J Obstet Gynecol. 2003;188:401-8).
The investigators initially looked at histology associated with endometrial thickness in 394 postmenopausal women referred for AUB between 1987 and 1990. Both transvaginal ultrasound and dilatation and curettage were performed, and the findings were correlated.
“But they had the rare opportunity to take patients who had benign evaluations and bring them back 10 years later,” Dr. Shwayder said. “What they found was that, regardless of the endometrial thickness, if it was benign initially and they did not bleed over that 10-year period, no one had cancer.”
However, among the patients followed for 10 years who had recurrent bleeding, 10% had cancer and 12% had hyperplasia. Thus, deciding against a biopsy in this case is supported by good data; if the patient doesn’t bleed, she has an “incredibly low risk of cancer,” he said.
“If they bleed again, you’ve gotta work ‘em up,” he stressed. “Don’t continue to say, ‘Well, let me repeat the ultrasound and see if it’s thinner or thicker.’ No. They need to be evaluated.”
Keep in mind that if a biopsy is performed as the first step, the chances of the results coming back as tissue insufficient for diagnosis (TIFD) are increased, and a repeat biopsy will be necessary because of the inconclusive findings, Dr. Shwayder said. It helps to warn a patient in advance that their thin endometrium makes it highly likely that a repeat biopsy will be necessary, as 90% come back as TIFD or atrophy.
Importantly, though, ACOG says endometrial sampling should be performed first line in patients over age 45 years with AUB.
“I’ll be honest – I use ultrasound in these patients because of the fact that a third will have some sort of structural defect, and the focal abnormalities are things we’re not going to be able to pick up with a straight biopsy, but we have to be cognizant that the college recommends biopsy in this population,” Dr. Shwayder said.
Asymptomatic endometrial thickening
Postmenopausal women are increasingly being referred for asymptomatic endometrial thickening that is found incidentally during an unrelated evaluation, Dr. Shwayder said, noting that evidence to date on how to approach such cases is conflicting.
Although ACOG is working on a recommendation, none is currently available, he said.
However, a 2001 study comparing 123 asymptomatic patients with 90 symptomatic patients, all with an endometrial thickness of greater than 10 mm, found no prognostic advantage to screening versus waiting until bleeding occurred, he noted (Euro J Cancer. 2001;37:64-71).
Overall, 13% of the patients had cancer, 50% had polyps, and 17% had hyperplasia.
“But what they emphasized was ... the length [of time] the patients complained of abnormal uterine bleeding. If it was less than 8 weeks ... there was no statistical difference in outcome, but if it was over 8 weeks there was a statistically significant difference in the grade of disease – a prognostic advantage for those patients who were screened versus symptomatic.”
The overall 5-year disease-free survival was 86% for asymptomatic versus 77% for symptomatic patients; for those with bleeding for less than 8 weeks, it was 98% versus 83%, respectively. The differences were not statistically different. However, for those with bleeding for 8-16 weeks it was 90% versus 74%, and for those with bleeding for more than 16 weeks it was 69% versus 62%, respectively, and those differences were statistically significant.
The problem is that many patients put off coming in for a long time, which means they are in a category with a worse prognosis when they do come in, Dr. Shwayder said. That’s not to say everyone should be screened, but there is no prognostic advantage to screening asymptomatic patients versus symptomatic patients who had bleeding for less than 8 weeks.
“It’s a little clarification, but I think an important one,” he noted.
Another study of 1,607 patients with endometrial thickening, including 233 who were asymptomatic and 1,374 who were symptomatic, found a lower rate of deep invasion with stage 1 disease, but no difference in the rate of more advanced disease, and no association with a more favorable outcome between the groups. (Am J Obstet Gynecol. 2018;219[2]:183e1-6).
Additionally, a study of 42 asymptomatic patients, 95 symptomatic patients with bleeding for less than 3 months, and 83 symptomatic patients with bleeding for more than 3 months showed a nonsignificant trend toward poorer 5-year survival in patients with a longer history of bleeding prior to surgery (Arch Gynecol Obstet 2013;288:1361-4).
“So now the question becomes how thick is too thick [and whether there is] some threshold where we ought to be evaluating patients and some threshold where we’re not,” he said.
The risk of malignancy among symptomatic postmenopausal women with an endometrial thickness greater than 5 mm is 7.3%, and the risk is similar at 6.7% in asymptomatic patients with an endometrial thickness of 11 mm or greater, according to a 2004 study by Smith-Bindman et al. (Ultrasound Obstet Gynecol. 2004;24:558-65).
“So the thought process here is that if a patient is asymptomatic, but the endometrium is over 11 mm, maybe we ought to evaluate that patient, because her risk of cancer is equivalent to that of someone who presents with postmenopausal bleeding and has an endometrium greater than 5 mm,” he explained.
In fact, a practice guideline from the Society of Obstetricians and Gynecologists of Canada recommends that women with endometrial thickness over 11 mm and other risk factors for cancer – such as obesity, hypertension, or late menopause – should be referred to a gynecologist for investigation, Dr. Shwayder said, adding that he also considers increased vascularity, heterogeneity in the endometrium, and fluid seen on a scan as cause for further evaluation.
“But endometrial sampling without bleeding should not be routinely performed,” he said. “So don’t routinely [sample] but based on risk factors and ultrasound findings, you may want to consider evaluating these patients further.”
Dr. Shwayder is a consultant for GE Ultrasound.
NASHVILLE, TENN. – Ultrasound is a reasonable first step for the evaluation of postmenopausal women with abnormal uterine bleeding and endometrial thickness up to 5 mm, according to James Shwayder, MD, JD.
About a third of such patients presenting with abnormal uterine bleeding (AUB) will have an endometrial polyp or submucous myoma, Dr. Shwayder explained during a presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
However, recurrent bleeding warrants further work-up, he said.
The 5-mm value is based on a number of studies, which, in sum, show that the negative predictive value for cancer for endometrial thickness less than 4 mm is greater than 99%, said Dr. Shwayder, chief of the division of gynecology and director of the fellowship in advanced endoscopy obstetrics, gynecology, and women’s health at the University of Louisville (Ky.).
“In fact ... the risk of cancer is 1 in 917,” he added. “That’s pretty good ... that’s a great screening tool.”
The question is whether one can feel comfortable foregoing biopsy in such cases, he said, describing a 61-year-old patient with a 3.9-mm endometrium and AUB for 3 days, 3 weeks prior to her visit.
There are two possibilities: The patient will either have no further bleeding, or she will continue to bleed, he said, noting that a 2003 Swedish study provides some guidance in the case of continued bleeding (Am J Obstet Gynecol. 2003;188:401-8).
The investigators initially looked at histology associated with endometrial thickness in 394 postmenopausal women referred for AUB between 1987 and 1990. Both transvaginal ultrasound and dilatation and curettage were performed, and the findings were correlated.
“But they had the rare opportunity to take patients who had benign evaluations and bring them back 10 years later,” Dr. Shwayder said. “What they found was that, regardless of the endometrial thickness, if it was benign initially and they did not bleed over that 10-year period, no one had cancer.”
However, among the patients followed for 10 years who had recurrent bleeding, 10% had cancer and 12% had hyperplasia. Thus, deciding against a biopsy in this case is supported by good data; if the patient doesn’t bleed, she has an “incredibly low risk of cancer,” he said.
“If they bleed again, you’ve gotta work ‘em up,” he stressed. “Don’t continue to say, ‘Well, let me repeat the ultrasound and see if it’s thinner or thicker.’ No. They need to be evaluated.”
Keep in mind that if a biopsy is performed as the first step, the chances of the results coming back as tissue insufficient for diagnosis (TIFD) are increased, and a repeat biopsy will be necessary because of the inconclusive findings, Dr. Shwayder said. It helps to warn a patient in advance that their thin endometrium makes it highly likely that a repeat biopsy will be necessary, as 90% come back as TIFD or atrophy.
Importantly, though, ACOG says endometrial sampling should be performed first line in patients over age 45 years with AUB.
“I’ll be honest – I use ultrasound in these patients because of the fact that a third will have some sort of structural defect, and the focal abnormalities are things we’re not going to be able to pick up with a straight biopsy, but we have to be cognizant that the college recommends biopsy in this population,” Dr. Shwayder said.
Asymptomatic endometrial thickening
Postmenopausal women are increasingly being referred for asymptomatic endometrial thickening that is found incidentally during an unrelated evaluation, Dr. Shwayder said, noting that evidence to date on how to approach such cases is conflicting.
Although ACOG is working on a recommendation, none is currently available, he said.
However, a 2001 study comparing 123 asymptomatic patients with 90 symptomatic patients, all with an endometrial thickness of greater than 10 mm, found no prognostic advantage to screening versus waiting until bleeding occurred, he noted (Euro J Cancer. 2001;37:64-71).
Overall, 13% of the patients had cancer, 50% had polyps, and 17% had hyperplasia.
“But what they emphasized was ... the length [of time] the patients complained of abnormal uterine bleeding. If it was less than 8 weeks ... there was no statistical difference in outcome, but if it was over 8 weeks there was a statistically significant difference in the grade of disease – a prognostic advantage for those patients who were screened versus symptomatic.”
The overall 5-year disease-free survival was 86% for asymptomatic versus 77% for symptomatic patients; for those with bleeding for less than 8 weeks, it was 98% versus 83%, respectively. The differences were not statistically different. However, for those with bleeding for 8-16 weeks it was 90% versus 74%, and for those with bleeding for more than 16 weeks it was 69% versus 62%, respectively, and those differences were statistically significant.
The problem is that many patients put off coming in for a long time, which means they are in a category with a worse prognosis when they do come in, Dr. Shwayder said. That’s not to say everyone should be screened, but there is no prognostic advantage to screening asymptomatic patients versus symptomatic patients who had bleeding for less than 8 weeks.
“It’s a little clarification, but I think an important one,” he noted.
Another study of 1,607 patients with endometrial thickening, including 233 who were asymptomatic and 1,374 who were symptomatic, found a lower rate of deep invasion with stage 1 disease, but no difference in the rate of more advanced disease, and no association with a more favorable outcome between the groups. (Am J Obstet Gynecol. 2018;219[2]:183e1-6).
Additionally, a study of 42 asymptomatic patients, 95 symptomatic patients with bleeding for less than 3 months, and 83 symptomatic patients with bleeding for more than 3 months showed a nonsignificant trend toward poorer 5-year survival in patients with a longer history of bleeding prior to surgery (Arch Gynecol Obstet 2013;288:1361-4).
“So now the question becomes how thick is too thick [and whether there is] some threshold where we ought to be evaluating patients and some threshold where we’re not,” he said.
The risk of malignancy among symptomatic postmenopausal women with an endometrial thickness greater than 5 mm is 7.3%, and the risk is similar at 6.7% in asymptomatic patients with an endometrial thickness of 11 mm or greater, according to a 2004 study by Smith-Bindman et al. (Ultrasound Obstet Gynecol. 2004;24:558-65).
“So the thought process here is that if a patient is asymptomatic, but the endometrium is over 11 mm, maybe we ought to evaluate that patient, because her risk of cancer is equivalent to that of someone who presents with postmenopausal bleeding and has an endometrium greater than 5 mm,” he explained.
In fact, a practice guideline from the Society of Obstetricians and Gynecologists of Canada recommends that women with endometrial thickness over 11 mm and other risk factors for cancer – such as obesity, hypertension, or late menopause – should be referred to a gynecologist for investigation, Dr. Shwayder said, adding that he also considers increased vascularity, heterogeneity in the endometrium, and fluid seen on a scan as cause for further evaluation.
“But endometrial sampling without bleeding should not be routinely performed,” he said. “So don’t routinely [sample] but based on risk factors and ultrasound findings, you may want to consider evaluating these patients further.”
Dr. Shwayder is a consultant for GE Ultrasound.
EXPERT ANALYSIS FROM ACOG 2019
Bilateral salpingectomy gains favor for sterilization
NASHVILLE, TENN. –
“[It is] probably the newest thing on the block ... this is becoming super widespread,” Eve Espey, MD, said of the procedure during a contraceptive update at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
Although evidence directly supporting bilateral salpingectomy for sterilization is lacking, there are good reasons to consider it, she said.
For example, the procedure is likely more effective than tubal ligation with no increased risk for complications, and is probably more likely to cut ovarian cancer risk than is tubal ligation, explained Dr. Espey, professor and chair of the department of obstetrics and gynecology and director of the family planning fellowship at the University of New Mexico, Albuquerque.
“So we don’t actually have good [randomized controlled trials] on effectiveness for [bilateral] salpingectomy, but it is most like a partial salpingectomy, which is highly effective, so there is reason to believe that it might be more effective,” she added. The downsides are that the procedure may take longer, it may impair ovarian blood supply, and long-term population-level data on outcomes are lacking.
ACOG said in a 2015 committee opinion that when counseling women, bilateral salpingectomy can be discussed and considered “a method that provides effective contraception,” but also stressed the need for randomized controlled trials to support any related reduction in ovarian cancer risk. That opinion (#620) was replaced in April 2019 by Committee Opinion #774, which addresses opportunistic salpingectomy for epithelial ovarian cancer prevention, and which states that “the risks and benefits of salpingectomy should be discussed with patients who desire permanent sterilization.”
“[The Society of Gynecologic Oncology] is much, much more emphatic,” Dr. Espey said, citing a 2013 Clinical Practice Statement calling for discussion and consideration of risk-reducing salpingectomy in lieu of tubal ligation for women at average risk of ovarian cancer (after childbearing).
Dr. Espey also noted that during a recent grand rounds on sterilization, about 90% of participants said they were doing bilateral salpingectomy in the setting of vaginal delivery. “So I think we’re going to see this coming not just with C-section, but also with vaginal delivery.”
Dr. Espey reported having no relevant financial disclosures.
NASHVILLE, TENN. –
“[It is] probably the newest thing on the block ... this is becoming super widespread,” Eve Espey, MD, said of the procedure during a contraceptive update at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
Although evidence directly supporting bilateral salpingectomy for sterilization is lacking, there are good reasons to consider it, she said.
For example, the procedure is likely more effective than tubal ligation with no increased risk for complications, and is probably more likely to cut ovarian cancer risk than is tubal ligation, explained Dr. Espey, professor and chair of the department of obstetrics and gynecology and director of the family planning fellowship at the University of New Mexico, Albuquerque.
“So we don’t actually have good [randomized controlled trials] on effectiveness for [bilateral] salpingectomy, but it is most like a partial salpingectomy, which is highly effective, so there is reason to believe that it might be more effective,” she added. The downsides are that the procedure may take longer, it may impair ovarian blood supply, and long-term population-level data on outcomes are lacking.
ACOG said in a 2015 committee opinion that when counseling women, bilateral salpingectomy can be discussed and considered “a method that provides effective contraception,” but also stressed the need for randomized controlled trials to support any related reduction in ovarian cancer risk. That opinion (#620) was replaced in April 2019 by Committee Opinion #774, which addresses opportunistic salpingectomy for epithelial ovarian cancer prevention, and which states that “the risks and benefits of salpingectomy should be discussed with patients who desire permanent sterilization.”
“[The Society of Gynecologic Oncology] is much, much more emphatic,” Dr. Espey said, citing a 2013 Clinical Practice Statement calling for discussion and consideration of risk-reducing salpingectomy in lieu of tubal ligation for women at average risk of ovarian cancer (after childbearing).
Dr. Espey also noted that during a recent grand rounds on sterilization, about 90% of participants said they were doing bilateral salpingectomy in the setting of vaginal delivery. “So I think we’re going to see this coming not just with C-section, but also with vaginal delivery.”
Dr. Espey reported having no relevant financial disclosures.
NASHVILLE, TENN. –
“[It is] probably the newest thing on the block ... this is becoming super widespread,” Eve Espey, MD, said of the procedure during a contraceptive update at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
Although evidence directly supporting bilateral salpingectomy for sterilization is lacking, there are good reasons to consider it, she said.
For example, the procedure is likely more effective than tubal ligation with no increased risk for complications, and is probably more likely to cut ovarian cancer risk than is tubal ligation, explained Dr. Espey, professor and chair of the department of obstetrics and gynecology and director of the family planning fellowship at the University of New Mexico, Albuquerque.
“So we don’t actually have good [randomized controlled trials] on effectiveness for [bilateral] salpingectomy, but it is most like a partial salpingectomy, which is highly effective, so there is reason to believe that it might be more effective,” she added. The downsides are that the procedure may take longer, it may impair ovarian blood supply, and long-term population-level data on outcomes are lacking.
ACOG said in a 2015 committee opinion that when counseling women, bilateral salpingectomy can be discussed and considered “a method that provides effective contraception,” but also stressed the need for randomized controlled trials to support any related reduction in ovarian cancer risk. That opinion (#620) was replaced in April 2019 by Committee Opinion #774, which addresses opportunistic salpingectomy for epithelial ovarian cancer prevention, and which states that “the risks and benefits of salpingectomy should be discussed with patients who desire permanent sterilization.”
“[The Society of Gynecologic Oncology] is much, much more emphatic,” Dr. Espey said, citing a 2013 Clinical Practice Statement calling for discussion and consideration of risk-reducing salpingectomy in lieu of tubal ligation for women at average risk of ovarian cancer (after childbearing).
Dr. Espey also noted that during a recent grand rounds on sterilization, about 90% of participants said they were doing bilateral salpingectomy in the setting of vaginal delivery. “So I think we’re going to see this coming not just with C-section, but also with vaginal delivery.”
Dr. Espey reported having no relevant financial disclosures.
EXPERT COMMENTARY FROM ACOG 2019
The FDA has revised its guidance on fish consumption
The revision touts the health benefits of fish and shellfish and promotes safer fish choices for those who should limit mercury exposure – including women who are or might become pregnant, women who are breastfeeding, and young children.
Those individuals should avoid commercial fish with the highest levels of mercury and should instead choose from “the many types of fish that are lower in mercury – including ones commonly found in grocery stores, such as salmon, shrimp, pollock, canned light tuna, tilapia, catfish, and cod,” according to an FDA press statement.
The potential health benefits of eating fish were highlighted in the U.S. Department of Health and Human Services/Department of Agriculture 2015-2020 Dietary Guidelines for Americans, and in 2017 the FDA and the Environmental Protection Agency released advice on fish consumption, including a user-friendly reference chart regarding mercury levels in various types of fish.
Although the information in the chart has not changed, the FDA revised its advice to expand on the “information about the benefits of fish as part of healthy eating patterns by promoting the science-based recommendations of the 2015-2020 Dietary Guidelines for Americans.”
The advice calls for consumption of at least 8 ounces of seafood per week for adults (less for children) based on a 2,000 calorie diet, and for women who are pregnant or breastfeeding, 8-12 ounces of a variety of seafood per week selected from choices lower in mercury.
“The FDA’s revised advice highlights the many nutrients found in fish, several of which have important roles in growth and development during pregnancy and early childhood. It also highlights the potential health benefits of eating fish as part of a healthy eating pattern, particularly for improving heart health and lowering the risk of obesity,” the press release states.
Despite these benefits – and the recommendations for intake – concerns about mercury in fish have led many pregnant women in the United States to consume far less than the recommended amount of seafood, according to Susan Mayne, PhD, director of the FDA’s Center for Food Safety and Applied Nutrition.
“Our goal is to make sure Americans are equipped with this knowledge so that they can reap the benefits of eating fish, while choosing types of fish that are safe for them and their families to eat,” Dr. Mayne said in the FDA statement.
In response to the revised guidance, John S. Cullen, MD, president of the American Academy of Family Physicians, said that all women should be counseled to eat a well-balanced and varied diet including meats, dairy products, fruits, vegetables, and grains, and pregnant women should limit their intake of fish and seafood products to 8-12 ounces, or about 2-3 fish meals, per week.
Pregnant women may eat salmon in moderation, but should avoid raw seafood of any type because of possible contamination with parasites and Norwalk-like viruses, he said, adding that seafood like shark, swordfish, king mackerel, tilefish, Bigeye (Ahi) tuna steaks, and other long-lived fish high on the food chain should be avoided completely because of high mercury levels.
“While the AAFP did not review the revised advice to the dietary guidelines, family physicians are on the front lines encouraging healthy nutrition for pregnant and breastfeeding women and young children. It’s an ongoing, important part of the patient-physician conversation that begins with the initial prenatal visit,” Dr. Cullen said in a statement.
Similarly, Christopher M. Zahn, MD, vice president of practice activities for the American College of Obstetricians and Gynecologists, said the FDA/EPA updated guidance is in line with ACOG recommendations.
“The guidance continues to underscore the value of eating seafood 2-3 times per week during pregnancy and the importance of avoiding fish products that are high in mercury. The additional emphasis on healthy eating patterns mirrors ACOG’s long-standing guidance on the importance of a well-balanced, varied, nutritional diet that is consistent with a woman’s access to food and food preferences,” he said in a statement, noting that “seafood is a nutrient-rich food that has proven beneficial to women and in aiding the development of a fetus throughout pregnancy.”
The revision touts the health benefits of fish and shellfish and promotes safer fish choices for those who should limit mercury exposure – including women who are or might become pregnant, women who are breastfeeding, and young children.
Those individuals should avoid commercial fish with the highest levels of mercury and should instead choose from “the many types of fish that are lower in mercury – including ones commonly found in grocery stores, such as salmon, shrimp, pollock, canned light tuna, tilapia, catfish, and cod,” according to an FDA press statement.
The potential health benefits of eating fish were highlighted in the U.S. Department of Health and Human Services/Department of Agriculture 2015-2020 Dietary Guidelines for Americans, and in 2017 the FDA and the Environmental Protection Agency released advice on fish consumption, including a user-friendly reference chart regarding mercury levels in various types of fish.
Although the information in the chart has not changed, the FDA revised its advice to expand on the “information about the benefits of fish as part of healthy eating patterns by promoting the science-based recommendations of the 2015-2020 Dietary Guidelines for Americans.”
The advice calls for consumption of at least 8 ounces of seafood per week for adults (less for children) based on a 2,000 calorie diet, and for women who are pregnant or breastfeeding, 8-12 ounces of a variety of seafood per week selected from choices lower in mercury.
“The FDA’s revised advice highlights the many nutrients found in fish, several of which have important roles in growth and development during pregnancy and early childhood. It also highlights the potential health benefits of eating fish as part of a healthy eating pattern, particularly for improving heart health and lowering the risk of obesity,” the press release states.
Despite these benefits – and the recommendations for intake – concerns about mercury in fish have led many pregnant women in the United States to consume far less than the recommended amount of seafood, according to Susan Mayne, PhD, director of the FDA’s Center for Food Safety and Applied Nutrition.
“Our goal is to make sure Americans are equipped with this knowledge so that they can reap the benefits of eating fish, while choosing types of fish that are safe for them and their families to eat,” Dr. Mayne said in the FDA statement.
In response to the revised guidance, John S. Cullen, MD, president of the American Academy of Family Physicians, said that all women should be counseled to eat a well-balanced and varied diet including meats, dairy products, fruits, vegetables, and grains, and pregnant women should limit their intake of fish and seafood products to 8-12 ounces, or about 2-3 fish meals, per week.
Pregnant women may eat salmon in moderation, but should avoid raw seafood of any type because of possible contamination with parasites and Norwalk-like viruses, he said, adding that seafood like shark, swordfish, king mackerel, tilefish, Bigeye (Ahi) tuna steaks, and other long-lived fish high on the food chain should be avoided completely because of high mercury levels.
“While the AAFP did not review the revised advice to the dietary guidelines, family physicians are on the front lines encouraging healthy nutrition for pregnant and breastfeeding women and young children. It’s an ongoing, important part of the patient-physician conversation that begins with the initial prenatal visit,” Dr. Cullen said in a statement.
Similarly, Christopher M. Zahn, MD, vice president of practice activities for the American College of Obstetricians and Gynecologists, said the FDA/EPA updated guidance is in line with ACOG recommendations.
“The guidance continues to underscore the value of eating seafood 2-3 times per week during pregnancy and the importance of avoiding fish products that are high in mercury. The additional emphasis on healthy eating patterns mirrors ACOG’s long-standing guidance on the importance of a well-balanced, varied, nutritional diet that is consistent with a woman’s access to food and food preferences,” he said in a statement, noting that “seafood is a nutrient-rich food that has proven beneficial to women and in aiding the development of a fetus throughout pregnancy.”
The revision touts the health benefits of fish and shellfish and promotes safer fish choices for those who should limit mercury exposure – including women who are or might become pregnant, women who are breastfeeding, and young children.
Those individuals should avoid commercial fish with the highest levels of mercury and should instead choose from “the many types of fish that are lower in mercury – including ones commonly found in grocery stores, such as salmon, shrimp, pollock, canned light tuna, tilapia, catfish, and cod,” according to an FDA press statement.
The potential health benefits of eating fish were highlighted in the U.S. Department of Health and Human Services/Department of Agriculture 2015-2020 Dietary Guidelines for Americans, and in 2017 the FDA and the Environmental Protection Agency released advice on fish consumption, including a user-friendly reference chart regarding mercury levels in various types of fish.
Although the information in the chart has not changed, the FDA revised its advice to expand on the “information about the benefits of fish as part of healthy eating patterns by promoting the science-based recommendations of the 2015-2020 Dietary Guidelines for Americans.”
The advice calls for consumption of at least 8 ounces of seafood per week for adults (less for children) based on a 2,000 calorie diet, and for women who are pregnant or breastfeeding, 8-12 ounces of a variety of seafood per week selected from choices lower in mercury.
“The FDA’s revised advice highlights the many nutrients found in fish, several of which have important roles in growth and development during pregnancy and early childhood. It also highlights the potential health benefits of eating fish as part of a healthy eating pattern, particularly for improving heart health and lowering the risk of obesity,” the press release states.
Despite these benefits – and the recommendations for intake – concerns about mercury in fish have led many pregnant women in the United States to consume far less than the recommended amount of seafood, according to Susan Mayne, PhD, director of the FDA’s Center for Food Safety and Applied Nutrition.
“Our goal is to make sure Americans are equipped with this knowledge so that they can reap the benefits of eating fish, while choosing types of fish that are safe for them and their families to eat,” Dr. Mayne said in the FDA statement.
In response to the revised guidance, John S. Cullen, MD, president of the American Academy of Family Physicians, said that all women should be counseled to eat a well-balanced and varied diet including meats, dairy products, fruits, vegetables, and grains, and pregnant women should limit their intake of fish and seafood products to 8-12 ounces, or about 2-3 fish meals, per week.
Pregnant women may eat salmon in moderation, but should avoid raw seafood of any type because of possible contamination with parasites and Norwalk-like viruses, he said, adding that seafood like shark, swordfish, king mackerel, tilefish, Bigeye (Ahi) tuna steaks, and other long-lived fish high on the food chain should be avoided completely because of high mercury levels.
“While the AAFP did not review the revised advice to the dietary guidelines, family physicians are on the front lines encouraging healthy nutrition for pregnant and breastfeeding women and young children. It’s an ongoing, important part of the patient-physician conversation that begins with the initial prenatal visit,” Dr. Cullen said in a statement.
Similarly, Christopher M. Zahn, MD, vice president of practice activities for the American College of Obstetricians and Gynecologists, said the FDA/EPA updated guidance is in line with ACOG recommendations.
“The guidance continues to underscore the value of eating seafood 2-3 times per week during pregnancy and the importance of avoiding fish products that are high in mercury. The additional emphasis on healthy eating patterns mirrors ACOG’s long-standing guidance on the importance of a well-balanced, varied, nutritional diet that is consistent with a woman’s access to food and food preferences,” he said in a statement, noting that “seafood is a nutrient-rich food that has proven beneficial to women and in aiding the development of a fetus throughout pregnancy.”
Claims data suggest endometriosis ups risk of chronic opioid use
NASHVILLE, TENN. – Women with endometriosis are at increased risk of chronic opioid use, compared with those without endometriosis, based on an analysis of claims data.
The 2-year rate of chronic opioid use was 4.4% among 36,373 women with endometriosis, compared with 1.1% among 2,172,936 women without endometriosis (odds ratio, 3.94) – a finding with important implications for physician prescribing considerations, Stephanie E. Chiuve, ScD, reported at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
The OR was 3.76 after adjusting for age, race, and geographic region, said Dr. Chiuve of AbbVie, North Chicago.
Notably, the prevalence of other pain conditions, depression, anxiety, abuse of substances other than opioids, immunologic disorders, and use of opioids and other medications at baseline was higher in women with endometriosis versus those without. In any year, women with endometriosis were twice as likely to fill at least one opioid prescription, and were 3.5-4 times more likely to be a chronic opioid user than were women without endometriosis, she and her colleagues wrote in a poster presented at the meeting.
“Up to 60% of women with endometriosis experience significant chronic pain, including dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia,” they explained, adding that opioids may be prescribed for chronic pain management or for acute pain in the context of surgical procedures for endometriosis.
“This was due in part to various comorbidities that are also risk factors for chronic opioid use,” Dr. Chiuve said.
Women included in the study were aged 18-50 years (mean, 35 years), and were identified from a U.S. commercial insurance claims database and followed for 2 years after enrolling between January 2006 and December 2017. Chronic opioid use was defined as at least 120 days covered by an opioid dispensing or at least 10 fills of an opioid over a 1-year period during the 2-year follow-up study.
“With a less restrictive definition of chronic opioid use [of at least 6 fills] in any given year, the OR for chronic use comparing women with endometriosis to [the referent group] was similar [OR, 3.77],” the investigators wrote. “The OR for chronic use was attenuated to 2.88 after further adjustment for comorbidities and other medication use.”
Women with endometriosis in this study also experienced higher rates of opioid-associated clinical sequelae, they noted. For example, the adjusted ORs were 17.71 for an opioid dependence diagnosis, 12.52 for opioid overdose, and 10.39 for opioid use disorder treatment in chronic versus nonchronic users of opioids.
Additionally, chronic users were more likely to be prescribed high dose opioids (aOR, 6.45) and to be coprescribed benzodiazepines and sedatives (aORs, 5.87 and 3.78, respectively).
In fact, the findings of this study – though limited by factors such as the use of prescription fills rather than intake to measure exposure, and possible misclassification of endometriosis because of a lack of billing claims or undiagnosed disease – raise concerns about harmful opioid-related outcomes and dangerous prescribing patterns, they said.
In a separate poster presentation at the meeting, the researchers reported that independent risk factors for chronic opioid use in this study population were younger age (ORs, 0.90 and 0.72 for those aged 25-35 and 35-40 years, respectively, vs. those under age 25 years); concomitant chronic pain conditions, including fibromyalgia (OR, 1.49), chronic back pain (OR, 1.55), headaches/migraines (OR, 1.49), irritable bowel syndrome (OR, 1.61), and rheumatoid arthritis (OR, 2.52); the use of antipsychiatric drugs, including antidepressants (OR, 2.0), antipsychotics (OR, 1.66), and benzodiazepines (OR, 1.87); and baseline opioid use (OR, 3.95).
Hispanic ethnicity and Asian race predicted lower risk of chronic opioid use (ORs, 0.56 and 0.39, respectively), they found.
“These data contribute to the knowledge of potential risks of opioid use and may inform benefit-risk decision making of opioid use among women with endometriosis for management of endometriosis and its associated pain,” they concluded.
This study was funded by AbbVie. Dr. Chiuve is an employee of AbbVie, and she reported receiving stock/stock options.
NASHVILLE, TENN. – Women with endometriosis are at increased risk of chronic opioid use, compared with those without endometriosis, based on an analysis of claims data.
The 2-year rate of chronic opioid use was 4.4% among 36,373 women with endometriosis, compared with 1.1% among 2,172,936 women without endometriosis (odds ratio, 3.94) – a finding with important implications for physician prescribing considerations, Stephanie E. Chiuve, ScD, reported at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
The OR was 3.76 after adjusting for age, race, and geographic region, said Dr. Chiuve of AbbVie, North Chicago.
Notably, the prevalence of other pain conditions, depression, anxiety, abuse of substances other than opioids, immunologic disorders, and use of opioids and other medications at baseline was higher in women with endometriosis versus those without. In any year, women with endometriosis were twice as likely to fill at least one opioid prescription, and were 3.5-4 times more likely to be a chronic opioid user than were women without endometriosis, she and her colleagues wrote in a poster presented at the meeting.
“Up to 60% of women with endometriosis experience significant chronic pain, including dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia,” they explained, adding that opioids may be prescribed for chronic pain management or for acute pain in the context of surgical procedures for endometriosis.
“This was due in part to various comorbidities that are also risk factors for chronic opioid use,” Dr. Chiuve said.
Women included in the study were aged 18-50 years (mean, 35 years), and were identified from a U.S. commercial insurance claims database and followed for 2 years after enrolling between January 2006 and December 2017. Chronic opioid use was defined as at least 120 days covered by an opioid dispensing or at least 10 fills of an opioid over a 1-year period during the 2-year follow-up study.
“With a less restrictive definition of chronic opioid use [of at least 6 fills] in any given year, the OR for chronic use comparing women with endometriosis to [the referent group] was similar [OR, 3.77],” the investigators wrote. “The OR for chronic use was attenuated to 2.88 after further adjustment for comorbidities and other medication use.”
Women with endometriosis in this study also experienced higher rates of opioid-associated clinical sequelae, they noted. For example, the adjusted ORs were 17.71 for an opioid dependence diagnosis, 12.52 for opioid overdose, and 10.39 for opioid use disorder treatment in chronic versus nonchronic users of opioids.
Additionally, chronic users were more likely to be prescribed high dose opioids (aOR, 6.45) and to be coprescribed benzodiazepines and sedatives (aORs, 5.87 and 3.78, respectively).
In fact, the findings of this study – though limited by factors such as the use of prescription fills rather than intake to measure exposure, and possible misclassification of endometriosis because of a lack of billing claims or undiagnosed disease – raise concerns about harmful opioid-related outcomes and dangerous prescribing patterns, they said.
In a separate poster presentation at the meeting, the researchers reported that independent risk factors for chronic opioid use in this study population were younger age (ORs, 0.90 and 0.72 for those aged 25-35 and 35-40 years, respectively, vs. those under age 25 years); concomitant chronic pain conditions, including fibromyalgia (OR, 1.49), chronic back pain (OR, 1.55), headaches/migraines (OR, 1.49), irritable bowel syndrome (OR, 1.61), and rheumatoid arthritis (OR, 2.52); the use of antipsychiatric drugs, including antidepressants (OR, 2.0), antipsychotics (OR, 1.66), and benzodiazepines (OR, 1.87); and baseline opioid use (OR, 3.95).
Hispanic ethnicity and Asian race predicted lower risk of chronic opioid use (ORs, 0.56 and 0.39, respectively), they found.
“These data contribute to the knowledge of potential risks of opioid use and may inform benefit-risk decision making of opioid use among women with endometriosis for management of endometriosis and its associated pain,” they concluded.
This study was funded by AbbVie. Dr. Chiuve is an employee of AbbVie, and she reported receiving stock/stock options.
NASHVILLE, TENN. – Women with endometriosis are at increased risk of chronic opioid use, compared with those without endometriosis, based on an analysis of claims data.
The 2-year rate of chronic opioid use was 4.4% among 36,373 women with endometriosis, compared with 1.1% among 2,172,936 women without endometriosis (odds ratio, 3.94) – a finding with important implications for physician prescribing considerations, Stephanie E. Chiuve, ScD, reported at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
The OR was 3.76 after adjusting for age, race, and geographic region, said Dr. Chiuve of AbbVie, North Chicago.
Notably, the prevalence of other pain conditions, depression, anxiety, abuse of substances other than opioids, immunologic disorders, and use of opioids and other medications at baseline was higher in women with endometriosis versus those without. In any year, women with endometriosis were twice as likely to fill at least one opioid prescription, and were 3.5-4 times more likely to be a chronic opioid user than were women without endometriosis, she and her colleagues wrote in a poster presented at the meeting.
“Up to 60% of women with endometriosis experience significant chronic pain, including dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia,” they explained, adding that opioids may be prescribed for chronic pain management or for acute pain in the context of surgical procedures for endometriosis.
“This was due in part to various comorbidities that are also risk factors for chronic opioid use,” Dr. Chiuve said.
Women included in the study were aged 18-50 years (mean, 35 years), and were identified from a U.S. commercial insurance claims database and followed for 2 years after enrolling between January 2006 and December 2017. Chronic opioid use was defined as at least 120 days covered by an opioid dispensing or at least 10 fills of an opioid over a 1-year period during the 2-year follow-up study.
“With a less restrictive definition of chronic opioid use [of at least 6 fills] in any given year, the OR for chronic use comparing women with endometriosis to [the referent group] was similar [OR, 3.77],” the investigators wrote. “The OR for chronic use was attenuated to 2.88 after further adjustment for comorbidities and other medication use.”
Women with endometriosis in this study also experienced higher rates of opioid-associated clinical sequelae, they noted. For example, the adjusted ORs were 17.71 for an opioid dependence diagnosis, 12.52 for opioid overdose, and 10.39 for opioid use disorder treatment in chronic versus nonchronic users of opioids.
Additionally, chronic users were more likely to be prescribed high dose opioids (aOR, 6.45) and to be coprescribed benzodiazepines and sedatives (aORs, 5.87 and 3.78, respectively).
In fact, the findings of this study – though limited by factors such as the use of prescription fills rather than intake to measure exposure, and possible misclassification of endometriosis because of a lack of billing claims or undiagnosed disease – raise concerns about harmful opioid-related outcomes and dangerous prescribing patterns, they said.
In a separate poster presentation at the meeting, the researchers reported that independent risk factors for chronic opioid use in this study population were younger age (ORs, 0.90 and 0.72 for those aged 25-35 and 35-40 years, respectively, vs. those under age 25 years); concomitant chronic pain conditions, including fibromyalgia (OR, 1.49), chronic back pain (OR, 1.55), headaches/migraines (OR, 1.49), irritable bowel syndrome (OR, 1.61), and rheumatoid arthritis (OR, 2.52); the use of antipsychiatric drugs, including antidepressants (OR, 2.0), antipsychotics (OR, 1.66), and benzodiazepines (OR, 1.87); and baseline opioid use (OR, 3.95).
Hispanic ethnicity and Asian race predicted lower risk of chronic opioid use (ORs, 0.56 and 0.39, respectively), they found.
“These data contribute to the knowledge of potential risks of opioid use and may inform benefit-risk decision making of opioid use among women with endometriosis for management of endometriosis and its associated pain,” they concluded.
This study was funded by AbbVie. Dr. Chiuve is an employee of AbbVie, and she reported receiving stock/stock options.
REPORTING FROM ACOG 2019
Dr. Eve Espey: Some good news in her 2019 contraceptive update
NASHVILLE, TENN. – There’s some good news on the contraception and reproductive health front, according to a recent update from Eve Espey, MD.
The unintended pregnancy rate in the United States, including among adolescents and young women, is declining, and the U.S. abortion rate is at its lowest level since Roe v. Wade, she said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
A 2016 article based on 2008-2011 data showed that after hovering around 50% for nearly 3 decades, the unintended pregnancy rate dropped “for the first time in a very long period of time,” said Dr. Espey, professor and chair of the department of obstetrics & gynecology, division of family planning at the University of New Mexico, Albuquerque (N Engl J Med. 2016; 374[9]:843-52).
“It doesn’t look that impressive – it basically went down to 45%, but considering the scope and the number of women who are affected by unplanned pregnancy, this is actually a huge public health achievement,” she said. “And I think ... in the next cycles of the [Center for Disease Control and Prevention’s] National Survey of Family Growth ... we’ll hopefully continue to see this and potentially more [decline].”
As for abortion rates, an increase occurred following Roe v. Wade, but rates are now down to pre-Roe levels.
“One of the things that we know about the abortion rate is that the most important determinant ... is access to contraceptives,” Dr. Espey said, noting that both the abortion and unintended pregnancy rate declines are attributable to better and more consistent use of contraceptives, increased abstinence as teens are waiting longer to have sex, and the “meteoric rise in long-acting reversible contraceptive (LARC) use.”
Importantly, while improvements in public health have traditionally only impacted upper-class white women, a reduction is finally occurring in disparities with women of color, but those disparities still remain,” she added. “Just like we’re focusing so much on this relative to maternal mortality, the same kinds of disparities occur in access to reproductive health.”
Dr. Espey also provided updates on other aspects of contraception.
IUDs and other LARC methods
The use of LARCs increased from 2% of contraceptive types used by reproductive-aged women in 2002 to 12% in 2012. The majority of that change was in IUD use, with a small increase in implant use, she said, noting that the latest data from the 2015-2017 cycle of the National Survey of Family Growth shows that the rate is now up to 16%.
“The rise has been nothing that I ever imagined that I would see, certainly in my professional career,” she said.
The huge impact of LARCs on the unintended pregnancy rate is attributable to consistent effectiveness over time, compared with an increasing failure rate over time with short-acting contraceptive methods, she said, explaining that while the failure rate with oral contraceptives is about 8%-9% over the first 3 years, it increases to 53% at 8 years.
It’s a matter of looking at both “typical use” effectiveness and continuation rates: LARCs have continuation rates of about 75%-85%; Depot-Provera, for example, has a 25%-30% continuation rate at 1 year, she noted.
Dr. Espey also attributed the gains to improved access via the Affordable Care Act’s contraceptive mandate, which has been shown in numerous studies to have improved access and consistency of contraceptive use, but which is “currently being chipped away,” and to the federal Title X program that covers family planning care for low income women, including undocumented women.
“These two programs have made a huge impact for us, and I hope that we as ob.gyns. will continue to support them,” she said.
Reproductive justice
Despite their effectiveness, it is important to remember that LARC methods are not right for everyone, Dr. Espey said.
“It’s not all about effectiveness. Women have many reasons for accessing contraception, and our job is not to reduce unintended pregnancy. ... The idea really is that we empower women. ... We should really give choices and trust women to make the best choices for them,” she explained.
Barriers to IUD removal also should be eliminated, she noted, explaining that a woman who wants her IUD removed a month after insertion should have that option.
She said she has “changed her language,” from asking why a woman wants an $800 IUD removed after a month to asking whether she would like to hear about ways to make it better or if she is “just ready to have it removed.”
For those not interested in a discussion about birth control, she suggested providing information about the bedsider.org site.
“This is a great resource for patients,” she said, noting that it is available in both English and Spanish.
U.S. Medical Eligibility Criteria and Selected Practice Recommendations on contraceptive use
The MEC contraceptive guidance, a regularly updated, evidence-based project of the CDC, provides “best practices” information on candidate selection, or the “who” of contraceptive selection (who is a candidate for a particular method), Dr. Espy said, noting that it’s a “handy resource” for in-office use.
The SPR is more of a “how-to” guide that provides specifics on contraceptive use, such as when a woman can rely on the pill for contraception after she starts taking it, or how a woman should be followed after IUD placement, she said.
A free CDC app provides access to both.
Emergency contraception
The best overall emergency contraceptive method is the copper IUD, but often it is less accessible than oral methods, of which ulipristal acetate (ella), is the best choice, Dr. Espy said.
“Ulipristal is kind of a best-kept secret. It’s a selective estrogen-receptor modulator – it actually works better and longer than Plan B (levonorgestrel). What’s great about Plan B is that you can get it over the counter, but ulipristal delays ovulation longer,” she explained.
Contraceptives and obesity
Oral contraceptive efficacy is “so much more about adherence,” than about weight, she said.
With respect to the contraceptive patch, limited evidence suggests that obesity may reduce effectiveness, but “it’s still way better than barrier methods,” and for the contraceptive ring, no evidence suggests that obesity affects efficacy, she said.
For emergency contraception, evidence suggests that ulipristal is more effective than Plan B in women with high body mass index.
OTC contraceptive access
Pharmacy and OTC access are a good idea, Dr. Espy said.
“ACOG now supports both, which is great, and there are now a number of states where women can access contraception through the pharmacy. There are a lot of barriers there as well, and really the answer is OTC access,” she said. “There is a pill right now that is seeking [Food and Drug Administration] approval; it will be a progestin-only pill – the first one to be available over the counter, so I think this is something that we’ll see in the next 5-10 years.”
Additional future directions
One technology in development is a longer-acting injectable, such as a 6- or 9-month Depot-type shot.
Biodegradable implants also are in development. “What a cool idea – it just disappears in your arm, no need to remove it,” Dr. Espey said, adding that nonsurgical permanent sterilization is another possible advance, which would be “a holy grail.”
As for male contraception?
“I’ve been saying for about 25 years that in 5 years we’ll have a male contraceptive, so I’m not going to say it anymore with any kind of time frame, but it’s possible,” she said.
Dr. Espey reported having no financial disclosures.
NASHVILLE, TENN. – There’s some good news on the contraception and reproductive health front, according to a recent update from Eve Espey, MD.
The unintended pregnancy rate in the United States, including among adolescents and young women, is declining, and the U.S. abortion rate is at its lowest level since Roe v. Wade, she said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
A 2016 article based on 2008-2011 data showed that after hovering around 50% for nearly 3 decades, the unintended pregnancy rate dropped “for the first time in a very long period of time,” said Dr. Espey, professor and chair of the department of obstetrics & gynecology, division of family planning at the University of New Mexico, Albuquerque (N Engl J Med. 2016; 374[9]:843-52).
“It doesn’t look that impressive – it basically went down to 45%, but considering the scope and the number of women who are affected by unplanned pregnancy, this is actually a huge public health achievement,” she said. “And I think ... in the next cycles of the [Center for Disease Control and Prevention’s] National Survey of Family Growth ... we’ll hopefully continue to see this and potentially more [decline].”
As for abortion rates, an increase occurred following Roe v. Wade, but rates are now down to pre-Roe levels.
“One of the things that we know about the abortion rate is that the most important determinant ... is access to contraceptives,” Dr. Espey said, noting that both the abortion and unintended pregnancy rate declines are attributable to better and more consistent use of contraceptives, increased abstinence as teens are waiting longer to have sex, and the “meteoric rise in long-acting reversible contraceptive (LARC) use.”
Importantly, while improvements in public health have traditionally only impacted upper-class white women, a reduction is finally occurring in disparities with women of color, but those disparities still remain,” she added. “Just like we’re focusing so much on this relative to maternal mortality, the same kinds of disparities occur in access to reproductive health.”
Dr. Espey also provided updates on other aspects of contraception.
IUDs and other LARC methods
The use of LARCs increased from 2% of contraceptive types used by reproductive-aged women in 2002 to 12% in 2012. The majority of that change was in IUD use, with a small increase in implant use, she said, noting that the latest data from the 2015-2017 cycle of the National Survey of Family Growth shows that the rate is now up to 16%.
“The rise has been nothing that I ever imagined that I would see, certainly in my professional career,” she said.
The huge impact of LARCs on the unintended pregnancy rate is attributable to consistent effectiveness over time, compared with an increasing failure rate over time with short-acting contraceptive methods, she said, explaining that while the failure rate with oral contraceptives is about 8%-9% over the first 3 years, it increases to 53% at 8 years.
It’s a matter of looking at both “typical use” effectiveness and continuation rates: LARCs have continuation rates of about 75%-85%; Depot-Provera, for example, has a 25%-30% continuation rate at 1 year, she noted.
Dr. Espey also attributed the gains to improved access via the Affordable Care Act’s contraceptive mandate, which has been shown in numerous studies to have improved access and consistency of contraceptive use, but which is “currently being chipped away,” and to the federal Title X program that covers family planning care for low income women, including undocumented women.
“These two programs have made a huge impact for us, and I hope that we as ob.gyns. will continue to support them,” she said.
Reproductive justice
Despite their effectiveness, it is important to remember that LARC methods are not right for everyone, Dr. Espey said.
“It’s not all about effectiveness. Women have many reasons for accessing contraception, and our job is not to reduce unintended pregnancy. ... The idea really is that we empower women. ... We should really give choices and trust women to make the best choices for them,” she explained.
Barriers to IUD removal also should be eliminated, she noted, explaining that a woman who wants her IUD removed a month after insertion should have that option.
She said she has “changed her language,” from asking why a woman wants an $800 IUD removed after a month to asking whether she would like to hear about ways to make it better or if she is “just ready to have it removed.”
For those not interested in a discussion about birth control, she suggested providing information about the bedsider.org site.
“This is a great resource for patients,” she said, noting that it is available in both English and Spanish.
U.S. Medical Eligibility Criteria and Selected Practice Recommendations on contraceptive use
The MEC contraceptive guidance, a regularly updated, evidence-based project of the CDC, provides “best practices” information on candidate selection, or the “who” of contraceptive selection (who is a candidate for a particular method), Dr. Espy said, noting that it’s a “handy resource” for in-office use.
The SPR is more of a “how-to” guide that provides specifics on contraceptive use, such as when a woman can rely on the pill for contraception after she starts taking it, or how a woman should be followed after IUD placement, she said.
A free CDC app provides access to both.
Emergency contraception
The best overall emergency contraceptive method is the copper IUD, but often it is less accessible than oral methods, of which ulipristal acetate (ella), is the best choice, Dr. Espy said.
“Ulipristal is kind of a best-kept secret. It’s a selective estrogen-receptor modulator – it actually works better and longer than Plan B (levonorgestrel). What’s great about Plan B is that you can get it over the counter, but ulipristal delays ovulation longer,” she explained.
Contraceptives and obesity
Oral contraceptive efficacy is “so much more about adherence,” than about weight, she said.
With respect to the contraceptive patch, limited evidence suggests that obesity may reduce effectiveness, but “it’s still way better than barrier methods,” and for the contraceptive ring, no evidence suggests that obesity affects efficacy, she said.
For emergency contraception, evidence suggests that ulipristal is more effective than Plan B in women with high body mass index.
OTC contraceptive access
Pharmacy and OTC access are a good idea, Dr. Espy said.
“ACOG now supports both, which is great, and there are now a number of states where women can access contraception through the pharmacy. There are a lot of barriers there as well, and really the answer is OTC access,” she said. “There is a pill right now that is seeking [Food and Drug Administration] approval; it will be a progestin-only pill – the first one to be available over the counter, so I think this is something that we’ll see in the next 5-10 years.”
Additional future directions
One technology in development is a longer-acting injectable, such as a 6- or 9-month Depot-type shot.
Biodegradable implants also are in development. “What a cool idea – it just disappears in your arm, no need to remove it,” Dr. Espey said, adding that nonsurgical permanent sterilization is another possible advance, which would be “a holy grail.”
As for male contraception?
“I’ve been saying for about 25 years that in 5 years we’ll have a male contraceptive, so I’m not going to say it anymore with any kind of time frame, but it’s possible,” she said.
Dr. Espey reported having no financial disclosures.
NASHVILLE, TENN. – There’s some good news on the contraception and reproductive health front, according to a recent update from Eve Espey, MD.
The unintended pregnancy rate in the United States, including among adolescents and young women, is declining, and the U.S. abortion rate is at its lowest level since Roe v. Wade, she said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
A 2016 article based on 2008-2011 data showed that after hovering around 50% for nearly 3 decades, the unintended pregnancy rate dropped “for the first time in a very long period of time,” said Dr. Espey, professor and chair of the department of obstetrics & gynecology, division of family planning at the University of New Mexico, Albuquerque (N Engl J Med. 2016; 374[9]:843-52).
“It doesn’t look that impressive – it basically went down to 45%, but considering the scope and the number of women who are affected by unplanned pregnancy, this is actually a huge public health achievement,” she said. “And I think ... in the next cycles of the [Center for Disease Control and Prevention’s] National Survey of Family Growth ... we’ll hopefully continue to see this and potentially more [decline].”
As for abortion rates, an increase occurred following Roe v. Wade, but rates are now down to pre-Roe levels.
“One of the things that we know about the abortion rate is that the most important determinant ... is access to contraceptives,” Dr. Espey said, noting that both the abortion and unintended pregnancy rate declines are attributable to better and more consistent use of contraceptives, increased abstinence as teens are waiting longer to have sex, and the “meteoric rise in long-acting reversible contraceptive (LARC) use.”
Importantly, while improvements in public health have traditionally only impacted upper-class white women, a reduction is finally occurring in disparities with women of color, but those disparities still remain,” she added. “Just like we’re focusing so much on this relative to maternal mortality, the same kinds of disparities occur in access to reproductive health.”
Dr. Espey also provided updates on other aspects of contraception.
IUDs and other LARC methods
The use of LARCs increased from 2% of contraceptive types used by reproductive-aged women in 2002 to 12% in 2012. The majority of that change was in IUD use, with a small increase in implant use, she said, noting that the latest data from the 2015-2017 cycle of the National Survey of Family Growth shows that the rate is now up to 16%.
“The rise has been nothing that I ever imagined that I would see, certainly in my professional career,” she said.
The huge impact of LARCs on the unintended pregnancy rate is attributable to consistent effectiveness over time, compared with an increasing failure rate over time with short-acting contraceptive methods, she said, explaining that while the failure rate with oral contraceptives is about 8%-9% over the first 3 years, it increases to 53% at 8 years.
It’s a matter of looking at both “typical use” effectiveness and continuation rates: LARCs have continuation rates of about 75%-85%; Depot-Provera, for example, has a 25%-30% continuation rate at 1 year, she noted.
Dr. Espey also attributed the gains to improved access via the Affordable Care Act’s contraceptive mandate, which has been shown in numerous studies to have improved access and consistency of contraceptive use, but which is “currently being chipped away,” and to the federal Title X program that covers family planning care for low income women, including undocumented women.
“These two programs have made a huge impact for us, and I hope that we as ob.gyns. will continue to support them,” she said.
Reproductive justice
Despite their effectiveness, it is important to remember that LARC methods are not right for everyone, Dr. Espey said.
“It’s not all about effectiveness. Women have many reasons for accessing contraception, and our job is not to reduce unintended pregnancy. ... The idea really is that we empower women. ... We should really give choices and trust women to make the best choices for them,” she explained.
Barriers to IUD removal also should be eliminated, she noted, explaining that a woman who wants her IUD removed a month after insertion should have that option.
She said she has “changed her language,” from asking why a woman wants an $800 IUD removed after a month to asking whether she would like to hear about ways to make it better or if she is “just ready to have it removed.”
For those not interested in a discussion about birth control, she suggested providing information about the bedsider.org site.
“This is a great resource for patients,” she said, noting that it is available in both English and Spanish.
U.S. Medical Eligibility Criteria and Selected Practice Recommendations on contraceptive use
The MEC contraceptive guidance, a regularly updated, evidence-based project of the CDC, provides “best practices” information on candidate selection, or the “who” of contraceptive selection (who is a candidate for a particular method), Dr. Espy said, noting that it’s a “handy resource” for in-office use.
The SPR is more of a “how-to” guide that provides specifics on contraceptive use, such as when a woman can rely on the pill for contraception after she starts taking it, or how a woman should be followed after IUD placement, she said.
A free CDC app provides access to both.
Emergency contraception
The best overall emergency contraceptive method is the copper IUD, but often it is less accessible than oral methods, of which ulipristal acetate (ella), is the best choice, Dr. Espy said.
“Ulipristal is kind of a best-kept secret. It’s a selective estrogen-receptor modulator – it actually works better and longer than Plan B (levonorgestrel). What’s great about Plan B is that you can get it over the counter, but ulipristal delays ovulation longer,” she explained.
Contraceptives and obesity
Oral contraceptive efficacy is “so much more about adherence,” than about weight, she said.
With respect to the contraceptive patch, limited evidence suggests that obesity may reduce effectiveness, but “it’s still way better than barrier methods,” and for the contraceptive ring, no evidence suggests that obesity affects efficacy, she said.
For emergency contraception, evidence suggests that ulipristal is more effective than Plan B in women with high body mass index.
OTC contraceptive access
Pharmacy and OTC access are a good idea, Dr. Espy said.
“ACOG now supports both, which is great, and there are now a number of states where women can access contraception through the pharmacy. There are a lot of barriers there as well, and really the answer is OTC access,” she said. “There is a pill right now that is seeking [Food and Drug Administration] approval; it will be a progestin-only pill – the first one to be available over the counter, so I think this is something that we’ll see in the next 5-10 years.”
Additional future directions
One technology in development is a longer-acting injectable, such as a 6- or 9-month Depot-type shot.
Biodegradable implants also are in development. “What a cool idea – it just disappears in your arm, no need to remove it,” Dr. Espey said, adding that nonsurgical permanent sterilization is another possible advance, which would be “a holy grail.”
As for male contraception?
“I’ve been saying for about 25 years that in 5 years we’ll have a male contraceptive, so I’m not going to say it anymore with any kind of time frame, but it’s possible,” she said.
Dr. Espey reported having no financial disclosures.
EXPERT ANALYSIS FROM ACOG 2019
LARC prolongs interpregnancy intervals but doesn’t cut preterm birth risk
NASHVILLE, TENN. – when used between a first and second pregnancy, results of a retrospective cohort study suggest.
Of 35,754 women who had a first and second live birth between 2005 and 2015 and who received non-emergent care within 10 years of the first birth, 3,083 (9%) had evidence of interpregnancy LARC exposure and were significantly less likely to have short interpregnancy intervals than were 32,671 with either non-LARC contraceptive use or no record of contraceptive-related care (P less than .0001), Sara E. Simonsen, PhD, reported in a poster at the annual meeting of the American College of Obstetricians and Gynecologists.
Intervals in those with intrapartum LARC use were 12 months or less in 4% of women, 13-18 months in 8%, 19-24 months in 11%, and greater than 24 months in 13%.
However, preterm birth, which occurred in 7% of first births and 6% of second births, was not lower among those with LARC exposure vs. those with no contraceptive encounters after adjustment for interpregnancy interval and a number of demographic factors, including education, presence of father, mother’s age, Hispanic ethnicity, fetal anomalies, and preterm birth history (adjusted odds ratio, 1.13), said Dr. Simonsen, a certified nurse midwife at the University of Utah Hospital, Salt Lake City.
“Preterm birth, a live birth at less than 37 weeks’ gestation, is a major determinant of poor neonatal outcomes,” she and her colleagues wrote. “Short interpregnancy interval, defined as less than 18 months, is an important risk factor for preterm birth.”
Given the increasing number of U.S. women who use highly effective LARCs to space pregnancies, she and her colleagues performed a retrospective cohort study of electronic medical records from two large health systems and linked them with birth and fetal death records to explore the relationship between interpregnancy LARC and both interpregnancy interval and preterm birth in the subsequent pregnancy.
“We did find that women who used LARC between their pregnancies were less likely to have a short interpregnancy interval, but in adjusted models ... we found no association with intrapartum LARC use and preterm birth in the second birth,” Dr. Simonsen said during an e-poster presentation at the meeting.
In fact, preterm birth in the second birth was most strongly associated with a prior preterm birth – a finding consistent with the literature, she and her colleagues noted.
Although the findings are limited by the use of retrospective data not designed for research, the data came from a large population-based sample representing about 85% of Utah births, they said.
The findings suggest that while LARC use may not reduce preterm birth risk, it “may contribute favorably to outcomes to the extent that having optimal interpregnancy interval does,” they wrote.
“‘We feel that these findings support providers counseling women on the full range of contraception options in the postpartum and not pushing [intrauterine devices,]” Dr. Simonsen added.
The related topic of immediate postpartum LARC use was addressed by Eve Espey, MD, in a separate presentation at the meeting.
Dr .Espey, professor and chair of the department of obstetrics and gynecology and director of the family planning fellowship at the University of New Mexico, Albuquerque, reported that immediate postpartum insertion of an intrauterine device (IUD) is highly cost-effective despite an expulsion rate of between 10% and 30%. She also addressed the value of postpartum LARC for reducing rapid-repeat pregnancy rates.
Payment models for immediate postpartum LARC are “very cumbersome,” but at the university, a persistent effort over 4 years has led to success. Immediate postpartum LARC is offered to women with Medicaid coverage, and payment is received in about 97% of cases, she said, adding that efforts are underway to help other hospitals “troubleshoot the issues.”
The lack of private insurance coverage for immediate postpartum LARC remains a challenge, but Dr. Espey said she remains “super enthusiastic” about its use.
“I think it’s going to take another 5 years or so [for better coverage], and honestly I think what we really need is an inpatient LARC CPT code to make this happen,” she said, urging colleagues to advocate for that within their American College of Obstetricians and Gynecologists sections when possible.
Dr. Simonsen and Dr. Espey reported having no relevant disclosures.
NASHVILLE, TENN. – when used between a first and second pregnancy, results of a retrospective cohort study suggest.
Of 35,754 women who had a first and second live birth between 2005 and 2015 and who received non-emergent care within 10 years of the first birth, 3,083 (9%) had evidence of interpregnancy LARC exposure and were significantly less likely to have short interpregnancy intervals than were 32,671 with either non-LARC contraceptive use or no record of contraceptive-related care (P less than .0001), Sara E. Simonsen, PhD, reported in a poster at the annual meeting of the American College of Obstetricians and Gynecologists.
Intervals in those with intrapartum LARC use were 12 months or less in 4% of women, 13-18 months in 8%, 19-24 months in 11%, and greater than 24 months in 13%.
However, preterm birth, which occurred in 7% of first births and 6% of second births, was not lower among those with LARC exposure vs. those with no contraceptive encounters after adjustment for interpregnancy interval and a number of demographic factors, including education, presence of father, mother’s age, Hispanic ethnicity, fetal anomalies, and preterm birth history (adjusted odds ratio, 1.13), said Dr. Simonsen, a certified nurse midwife at the University of Utah Hospital, Salt Lake City.
“Preterm birth, a live birth at less than 37 weeks’ gestation, is a major determinant of poor neonatal outcomes,” she and her colleagues wrote. “Short interpregnancy interval, defined as less than 18 months, is an important risk factor for preterm birth.”
Given the increasing number of U.S. women who use highly effective LARCs to space pregnancies, she and her colleagues performed a retrospective cohort study of electronic medical records from two large health systems and linked them with birth and fetal death records to explore the relationship between interpregnancy LARC and both interpregnancy interval and preterm birth in the subsequent pregnancy.
“We did find that women who used LARC between their pregnancies were less likely to have a short interpregnancy interval, but in adjusted models ... we found no association with intrapartum LARC use and preterm birth in the second birth,” Dr. Simonsen said during an e-poster presentation at the meeting.
In fact, preterm birth in the second birth was most strongly associated with a prior preterm birth – a finding consistent with the literature, she and her colleagues noted.
Although the findings are limited by the use of retrospective data not designed for research, the data came from a large population-based sample representing about 85% of Utah births, they said.
The findings suggest that while LARC use may not reduce preterm birth risk, it “may contribute favorably to outcomes to the extent that having optimal interpregnancy interval does,” they wrote.
“‘We feel that these findings support providers counseling women on the full range of contraception options in the postpartum and not pushing [intrauterine devices,]” Dr. Simonsen added.
The related topic of immediate postpartum LARC use was addressed by Eve Espey, MD, in a separate presentation at the meeting.
Dr .Espey, professor and chair of the department of obstetrics and gynecology and director of the family planning fellowship at the University of New Mexico, Albuquerque, reported that immediate postpartum insertion of an intrauterine device (IUD) is highly cost-effective despite an expulsion rate of between 10% and 30%. She also addressed the value of postpartum LARC for reducing rapid-repeat pregnancy rates.
Payment models for immediate postpartum LARC are “very cumbersome,” but at the university, a persistent effort over 4 years has led to success. Immediate postpartum LARC is offered to women with Medicaid coverage, and payment is received in about 97% of cases, she said, adding that efforts are underway to help other hospitals “troubleshoot the issues.”
The lack of private insurance coverage for immediate postpartum LARC remains a challenge, but Dr. Espey said she remains “super enthusiastic” about its use.
“I think it’s going to take another 5 years or so [for better coverage], and honestly I think what we really need is an inpatient LARC CPT code to make this happen,” she said, urging colleagues to advocate for that within their American College of Obstetricians and Gynecologists sections when possible.
Dr. Simonsen and Dr. Espey reported having no relevant disclosures.
NASHVILLE, TENN. – when used between a first and second pregnancy, results of a retrospective cohort study suggest.
Of 35,754 women who had a first and second live birth between 2005 and 2015 and who received non-emergent care within 10 years of the first birth, 3,083 (9%) had evidence of interpregnancy LARC exposure and were significantly less likely to have short interpregnancy intervals than were 32,671 with either non-LARC contraceptive use or no record of contraceptive-related care (P less than .0001), Sara E. Simonsen, PhD, reported in a poster at the annual meeting of the American College of Obstetricians and Gynecologists.
Intervals in those with intrapartum LARC use were 12 months or less in 4% of women, 13-18 months in 8%, 19-24 months in 11%, and greater than 24 months in 13%.
However, preterm birth, which occurred in 7% of first births and 6% of second births, was not lower among those with LARC exposure vs. those with no contraceptive encounters after adjustment for interpregnancy interval and a number of demographic factors, including education, presence of father, mother’s age, Hispanic ethnicity, fetal anomalies, and preterm birth history (adjusted odds ratio, 1.13), said Dr. Simonsen, a certified nurse midwife at the University of Utah Hospital, Salt Lake City.
“Preterm birth, a live birth at less than 37 weeks’ gestation, is a major determinant of poor neonatal outcomes,” she and her colleagues wrote. “Short interpregnancy interval, defined as less than 18 months, is an important risk factor for preterm birth.”
Given the increasing number of U.S. women who use highly effective LARCs to space pregnancies, she and her colleagues performed a retrospective cohort study of electronic medical records from two large health systems and linked them with birth and fetal death records to explore the relationship between interpregnancy LARC and both interpregnancy interval and preterm birth in the subsequent pregnancy.
“We did find that women who used LARC between their pregnancies were less likely to have a short interpregnancy interval, but in adjusted models ... we found no association with intrapartum LARC use and preterm birth in the second birth,” Dr. Simonsen said during an e-poster presentation at the meeting.
In fact, preterm birth in the second birth was most strongly associated with a prior preterm birth – a finding consistent with the literature, she and her colleagues noted.
Although the findings are limited by the use of retrospective data not designed for research, the data came from a large population-based sample representing about 85% of Utah births, they said.
The findings suggest that while LARC use may not reduce preterm birth risk, it “may contribute favorably to outcomes to the extent that having optimal interpregnancy interval does,” they wrote.
“‘We feel that these findings support providers counseling women on the full range of contraception options in the postpartum and not pushing [intrauterine devices,]” Dr. Simonsen added.
The related topic of immediate postpartum LARC use was addressed by Eve Espey, MD, in a separate presentation at the meeting.
Dr .Espey, professor and chair of the department of obstetrics and gynecology and director of the family planning fellowship at the University of New Mexico, Albuquerque, reported that immediate postpartum insertion of an intrauterine device (IUD) is highly cost-effective despite an expulsion rate of between 10% and 30%. She also addressed the value of postpartum LARC for reducing rapid-repeat pregnancy rates.
Payment models for immediate postpartum LARC are “very cumbersome,” but at the university, a persistent effort over 4 years has led to success. Immediate postpartum LARC is offered to women with Medicaid coverage, and payment is received in about 97% of cases, she said, adding that efforts are underway to help other hospitals “troubleshoot the issues.”
The lack of private insurance coverage for immediate postpartum LARC remains a challenge, but Dr. Espey said she remains “super enthusiastic” about its use.
“I think it’s going to take another 5 years or so [for better coverage], and honestly I think what we really need is an inpatient LARC CPT code to make this happen,” she said, urging colleagues to advocate for that within their American College of Obstetricians and Gynecologists sections when possible.
Dr. Simonsen and Dr. Espey reported having no relevant disclosures.
REPORTING FROM ACOG 2019
Survey: Patient-provider communication regarding dyspareunia disappoints
NASHVILLE, TENN. – Many women with endometriosis experience dyspareunia, but they are largely unsatisfied when it comes to discussions with health care providers about their symptoms, the results of an online survey suggest.
Of 638 women with self-reported endometriosis who responded to the survey, 81% said they always or usually experience pain during intercourse, 51% described their pain as severe, and 49% said they experience pain lasting more than 24 hours, Roberta Renzelli-Cain, DO, reported during a poster session at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“The results of our survey suggest that said Dr. Renzelli-Cain, director of the West Virginia National Center of Excellence in Women’s Health and an ob.gyn. at West Virginia University, Morgantown.
In fact, survey responses suggested that dyspareunia has a marked impact on quality of life; 69% of respondents said they find sexual intercourse unpleasant, 31% said they always or usually avoid intercourse, 44% strongly agreed that dyspareunia has affected their relationship with their spouse or partner, 63% said they worry that their spouse or partner will leave, and 63% said they feel depressed because of their dyspareunia, she and her colleagues found.
Most respondents (88%) discussed their symptoms with health care providers (HCPs), and 85% did so with their ob.gyn. Among the other HCPs who respondents spoke with about their dyspareunia were primary care physicians, nurse practitioners, emergency department doctors, fertility specialists, and pain specialists.
Among the reasons given for avoiding discussions with HCPs about painful intercourse were embarrassment (34% of respondents), thinking nothing would help (26%), the physician was a man (5%), and a feeling that the provider was not understanding (3%).
Overall, 18% of respondents said they received no advice from their HCPs regarding how to deal with their dyspareunia, and 39% found nothing that their HCPs suggested to be effective.
Advice given by HCPs included surgery, lubricant use, over-the-counter pain medication, and trying different sexual positions. The percentages of respondents receiving this advice, and the percentages who considered the advice effective, respectively, were 46%, 25% for surgery; 32%, 21% for lubricant use; 36%, 18% for OTC medication; and 21%, 14% for trying different sexual positions, the investigators said.
Importantly, 42% of respondent said they felt it would be easier to discuss dyspareunia if their HCP initiated the subject.
The findings are notable given that 6%-10% of women of childbearing age are affected by endometriosis, and about 30% of those women have related dyspareunia – a “challenging symptom associated with lower sexual functioning, as well as lower self-esteem, and body image,” the investigators wrote.
The 24-question English-language survey was conducted online among women aged 19 years or older who reported having endometriosis and dyspareunia. Participants were recruited via a social network for women with endometriosis (MyEndometriosisTeam.com) and invited by e-mail to participate.
Of the 32,865 invited participants, 361 U.S.-based women and 277 women from outside the United States completed the survey. Most (83%) were aged 19-29 years.
In this online survey, the majority of women reported suboptimal communication with HCPs when seeking help for dyspareunia, the investigators said, concluding that “these results were similar between the U.S.- and non-U.S.–based women, highlighting the need for better medical communication between patients and HCPs, and better advice for patients regarding dyspareunia.”
Dr. Renzelli-Cain reported having no relevant financial disclosures.
NASHVILLE, TENN. – Many women with endometriosis experience dyspareunia, but they are largely unsatisfied when it comes to discussions with health care providers about their symptoms, the results of an online survey suggest.
Of 638 women with self-reported endometriosis who responded to the survey, 81% said they always or usually experience pain during intercourse, 51% described their pain as severe, and 49% said they experience pain lasting more than 24 hours, Roberta Renzelli-Cain, DO, reported during a poster session at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“The results of our survey suggest that said Dr. Renzelli-Cain, director of the West Virginia National Center of Excellence in Women’s Health and an ob.gyn. at West Virginia University, Morgantown.
In fact, survey responses suggested that dyspareunia has a marked impact on quality of life; 69% of respondents said they find sexual intercourse unpleasant, 31% said they always or usually avoid intercourse, 44% strongly agreed that dyspareunia has affected their relationship with their spouse or partner, 63% said they worry that their spouse or partner will leave, and 63% said they feel depressed because of their dyspareunia, she and her colleagues found.
Most respondents (88%) discussed their symptoms with health care providers (HCPs), and 85% did so with their ob.gyn. Among the other HCPs who respondents spoke with about their dyspareunia were primary care physicians, nurse practitioners, emergency department doctors, fertility specialists, and pain specialists.
Among the reasons given for avoiding discussions with HCPs about painful intercourse were embarrassment (34% of respondents), thinking nothing would help (26%), the physician was a man (5%), and a feeling that the provider was not understanding (3%).
Overall, 18% of respondents said they received no advice from their HCPs regarding how to deal with their dyspareunia, and 39% found nothing that their HCPs suggested to be effective.
Advice given by HCPs included surgery, lubricant use, over-the-counter pain medication, and trying different sexual positions. The percentages of respondents receiving this advice, and the percentages who considered the advice effective, respectively, were 46%, 25% for surgery; 32%, 21% for lubricant use; 36%, 18% for OTC medication; and 21%, 14% for trying different sexual positions, the investigators said.
Importantly, 42% of respondent said they felt it would be easier to discuss dyspareunia if their HCP initiated the subject.
The findings are notable given that 6%-10% of women of childbearing age are affected by endometriosis, and about 30% of those women have related dyspareunia – a “challenging symptom associated with lower sexual functioning, as well as lower self-esteem, and body image,” the investigators wrote.
The 24-question English-language survey was conducted online among women aged 19 years or older who reported having endometriosis and dyspareunia. Participants were recruited via a social network for women with endometriosis (MyEndometriosisTeam.com) and invited by e-mail to participate.
Of the 32,865 invited participants, 361 U.S.-based women and 277 women from outside the United States completed the survey. Most (83%) were aged 19-29 years.
In this online survey, the majority of women reported suboptimal communication with HCPs when seeking help for dyspareunia, the investigators said, concluding that “these results were similar between the U.S.- and non-U.S.–based women, highlighting the need for better medical communication between patients and HCPs, and better advice for patients regarding dyspareunia.”
Dr. Renzelli-Cain reported having no relevant financial disclosures.
NASHVILLE, TENN. – Many women with endometriosis experience dyspareunia, but they are largely unsatisfied when it comes to discussions with health care providers about their symptoms, the results of an online survey suggest.
Of 638 women with self-reported endometriosis who responded to the survey, 81% said they always or usually experience pain during intercourse, 51% described their pain as severe, and 49% said they experience pain lasting more than 24 hours, Roberta Renzelli-Cain, DO, reported during a poster session at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“The results of our survey suggest that said Dr. Renzelli-Cain, director of the West Virginia National Center of Excellence in Women’s Health and an ob.gyn. at West Virginia University, Morgantown.
In fact, survey responses suggested that dyspareunia has a marked impact on quality of life; 69% of respondents said they find sexual intercourse unpleasant, 31% said they always or usually avoid intercourse, 44% strongly agreed that dyspareunia has affected their relationship with their spouse or partner, 63% said they worry that their spouse or partner will leave, and 63% said they feel depressed because of their dyspareunia, she and her colleagues found.
Most respondents (88%) discussed their symptoms with health care providers (HCPs), and 85% did so with their ob.gyn. Among the other HCPs who respondents spoke with about their dyspareunia were primary care physicians, nurse practitioners, emergency department doctors, fertility specialists, and pain specialists.
Among the reasons given for avoiding discussions with HCPs about painful intercourse were embarrassment (34% of respondents), thinking nothing would help (26%), the physician was a man (5%), and a feeling that the provider was not understanding (3%).
Overall, 18% of respondents said they received no advice from their HCPs regarding how to deal with their dyspareunia, and 39% found nothing that their HCPs suggested to be effective.
Advice given by HCPs included surgery, lubricant use, over-the-counter pain medication, and trying different sexual positions. The percentages of respondents receiving this advice, and the percentages who considered the advice effective, respectively, were 46%, 25% for surgery; 32%, 21% for lubricant use; 36%, 18% for OTC medication; and 21%, 14% for trying different sexual positions, the investigators said.
Importantly, 42% of respondent said they felt it would be easier to discuss dyspareunia if their HCP initiated the subject.
The findings are notable given that 6%-10% of women of childbearing age are affected by endometriosis, and about 30% of those women have related dyspareunia – a “challenging symptom associated with lower sexual functioning, as well as lower self-esteem, and body image,” the investigators wrote.
The 24-question English-language survey was conducted online among women aged 19 years or older who reported having endometriosis and dyspareunia. Participants were recruited via a social network for women with endometriosis (MyEndometriosisTeam.com) and invited by e-mail to participate.
Of the 32,865 invited participants, 361 U.S.-based women and 277 women from outside the United States completed the survey. Most (83%) were aged 19-29 years.
In this online survey, the majority of women reported suboptimal communication with HCPs when seeking help for dyspareunia, the investigators said, concluding that “these results were similar between the U.S.- and non-U.S.–based women, highlighting the need for better medical communication between patients and HCPs, and better advice for patients regarding dyspareunia.”
Dr. Renzelli-Cain reported having no relevant financial disclosures.
REPORTING FROM ACOG 2019
APHINITY trial: Biomarker analysis IDs predictive, prognostic factors
CHICAGO – Higher levels of several immune markers confer better response and outcomes in patients with HER2-positive breast cancer treated with trastuzumab and pertuzumab, according to a comprehensive biomarker analysis of data from the randomized, phase 3 APHINITY trial.
APHINITY randomized 4,805 patients with HER2-positive breast cancer to adjuvant chemotherapy with trastuzumab plus either pertuzumab or placebo and demonstrated a small improvement of just 1.7% in invasive disease–free survival at 4 years with the addition of adjuvant pertuzumab. The current analysis involved a nested case-control assessment of 1,023 patient samples from the trial to identify “biomarkers beyond clinical parameters” that could identify subgroups of patients who might benefit more from the addition of pertuzumab, Ian E. Krop, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
The genomic and immune marker-based analysis included DNA, whole transcriptome, tumor-infiltrating lymphocytes (TILs), and HER2 analyses, and after adjustment for treatment, hormone receptor status, nodal status, age, and chemotherapy type. Topoisomerase II-alpha amplification and higher messenger RNA expression of an immune signature consisting of interferon-gamma (IFNG), programmed death-ligand 1 (PD-L1), and chemokine (C-X-C motif) ligand 9 (CXCL9) were associated with better prognosis (hazard ratios, 0.68 and 0.91, respectively), said Dr. Krop, associate chief of the division of breast oncology at the Susan F. Smith Center for Women’s Cancers and clinical research director of the breast oncology center at Dana-Farber Cancer Institute, both in Boston.
TILs also suggested better outcomes (HR, 0.91), and HER2 copy number of six or greater versus lower levels of HER2 copy number was also associated with better prognosis (HR, 0.68), he noted.
Conversely, PI3K/PTEN/AKT gene alterations and MYC and ZNF703 amplification each were associated with worse outcomes (HRs, 1.35, 1.61, and 1.62, respectively).
As for predictive value, no significant association was seen between any of the amplification events and benefit of pertuzumab, nor was an interaction seen between the three-gene signature and pertuzumab benefit, Dr. Krop said.
“But if you look at the individual genes and ... the highest quartiles of expression of these genes – particularly interferon gamma and CXCL9 – it did appear that there was a statistically significant improvement in the benefit of pertuzumab if you had the highest levels of these genes, compared to lower levels of these genes,” he added.
The hazard ratios for CXCL9 of 0%-75% and greater than 75%, for example, were 0.95 and 0.49, respectively.
The interaction P values for IFNG and CXCL9 were statistically significant, but a trend toward benefit with PD-L1 did not reach statistical significance, Dr. Krop noted.
As with IFNG and CXCL9, the highest quartiles of TILs also predicted greater pertuzumab benefit (HRs for TILs at 0-75% and greater than 75%, 0.95 and 0.35, respectively), and the association was highly significant (P = .003).
HER2 copy number of six or greater was also associated with significantly greater benefit with pertuzumab (HRs for copy number of six or greater vs. less than six, 0.75 and 1.41, respectively).
A trend was seen toward decreased benefit of pertuzumab in patients with P13K/PTEN/AKT alteration, but this was not statistically significant, he noted.
However, the trend, coupled with the poor prognosis found to be associated with P13K-altered cancers, “would suggest that we need to identify new therapies – alternative approaches – to maximize treatment benefit in this cancer subtype,” he said.
“This biomarker analysis is possibly the largest and most comprehensive to date in HER2-positive breast cancer,” Dr. Krop said, noting that the findings provide support for an immune-mediated mechanism of action for pertuzumab, and suggest a need for alternative therapies for patients with low levels of TILs or immune gene markers in order to maximize their outcomes.
“We hope these data will be useful to refine future trials of early-stage HER2-positive breast cancer,” he said.
Dr. Krop reported relationships – including employment, leadership, and stock ownership – with AMAG, as well as honoraria from Genentech/Roche; consulting or advisory roles with Context Therapeutics, Daiichi Sankyo, Genentech/Roche, MacroGenics, Seattle Genetics, and Taiho Pharmaceutical; and research funding from Genentech and Pfizer to his institution.
SOURCE: Krop IE et al. ASCO 2019, Abstract 1012 .
CHICAGO – Higher levels of several immune markers confer better response and outcomes in patients with HER2-positive breast cancer treated with trastuzumab and pertuzumab, according to a comprehensive biomarker analysis of data from the randomized, phase 3 APHINITY trial.
APHINITY randomized 4,805 patients with HER2-positive breast cancer to adjuvant chemotherapy with trastuzumab plus either pertuzumab or placebo and demonstrated a small improvement of just 1.7% in invasive disease–free survival at 4 years with the addition of adjuvant pertuzumab. The current analysis involved a nested case-control assessment of 1,023 patient samples from the trial to identify “biomarkers beyond clinical parameters” that could identify subgroups of patients who might benefit more from the addition of pertuzumab, Ian E. Krop, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
The genomic and immune marker-based analysis included DNA, whole transcriptome, tumor-infiltrating lymphocytes (TILs), and HER2 analyses, and after adjustment for treatment, hormone receptor status, nodal status, age, and chemotherapy type. Topoisomerase II-alpha amplification and higher messenger RNA expression of an immune signature consisting of interferon-gamma (IFNG), programmed death-ligand 1 (PD-L1), and chemokine (C-X-C motif) ligand 9 (CXCL9) were associated with better prognosis (hazard ratios, 0.68 and 0.91, respectively), said Dr. Krop, associate chief of the division of breast oncology at the Susan F. Smith Center for Women’s Cancers and clinical research director of the breast oncology center at Dana-Farber Cancer Institute, both in Boston.
TILs also suggested better outcomes (HR, 0.91), and HER2 copy number of six or greater versus lower levels of HER2 copy number was also associated with better prognosis (HR, 0.68), he noted.
Conversely, PI3K/PTEN/AKT gene alterations and MYC and ZNF703 amplification each were associated with worse outcomes (HRs, 1.35, 1.61, and 1.62, respectively).
As for predictive value, no significant association was seen between any of the amplification events and benefit of pertuzumab, nor was an interaction seen between the three-gene signature and pertuzumab benefit, Dr. Krop said.
“But if you look at the individual genes and ... the highest quartiles of expression of these genes – particularly interferon gamma and CXCL9 – it did appear that there was a statistically significant improvement in the benefit of pertuzumab if you had the highest levels of these genes, compared to lower levels of these genes,” he added.
The hazard ratios for CXCL9 of 0%-75% and greater than 75%, for example, were 0.95 and 0.49, respectively.
The interaction P values for IFNG and CXCL9 were statistically significant, but a trend toward benefit with PD-L1 did not reach statistical significance, Dr. Krop noted.
As with IFNG and CXCL9, the highest quartiles of TILs also predicted greater pertuzumab benefit (HRs for TILs at 0-75% and greater than 75%, 0.95 and 0.35, respectively), and the association was highly significant (P = .003).
HER2 copy number of six or greater was also associated with significantly greater benefit with pertuzumab (HRs for copy number of six or greater vs. less than six, 0.75 and 1.41, respectively).
A trend was seen toward decreased benefit of pertuzumab in patients with P13K/PTEN/AKT alteration, but this was not statistically significant, he noted.
However, the trend, coupled with the poor prognosis found to be associated with P13K-altered cancers, “would suggest that we need to identify new therapies – alternative approaches – to maximize treatment benefit in this cancer subtype,” he said.
“This biomarker analysis is possibly the largest and most comprehensive to date in HER2-positive breast cancer,” Dr. Krop said, noting that the findings provide support for an immune-mediated mechanism of action for pertuzumab, and suggest a need for alternative therapies for patients with low levels of TILs or immune gene markers in order to maximize their outcomes.
“We hope these data will be useful to refine future trials of early-stage HER2-positive breast cancer,” he said.
Dr. Krop reported relationships – including employment, leadership, and stock ownership – with AMAG, as well as honoraria from Genentech/Roche; consulting or advisory roles with Context Therapeutics, Daiichi Sankyo, Genentech/Roche, MacroGenics, Seattle Genetics, and Taiho Pharmaceutical; and research funding from Genentech and Pfizer to his institution.
SOURCE: Krop IE et al. ASCO 2019, Abstract 1012 .
CHICAGO – Higher levels of several immune markers confer better response and outcomes in patients with HER2-positive breast cancer treated with trastuzumab and pertuzumab, according to a comprehensive biomarker analysis of data from the randomized, phase 3 APHINITY trial.
APHINITY randomized 4,805 patients with HER2-positive breast cancer to adjuvant chemotherapy with trastuzumab plus either pertuzumab or placebo and demonstrated a small improvement of just 1.7% in invasive disease–free survival at 4 years with the addition of adjuvant pertuzumab. The current analysis involved a nested case-control assessment of 1,023 patient samples from the trial to identify “biomarkers beyond clinical parameters” that could identify subgroups of patients who might benefit more from the addition of pertuzumab, Ian E. Krop, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
The genomic and immune marker-based analysis included DNA, whole transcriptome, tumor-infiltrating lymphocytes (TILs), and HER2 analyses, and after adjustment for treatment, hormone receptor status, nodal status, age, and chemotherapy type. Topoisomerase II-alpha amplification and higher messenger RNA expression of an immune signature consisting of interferon-gamma (IFNG), programmed death-ligand 1 (PD-L1), and chemokine (C-X-C motif) ligand 9 (CXCL9) were associated with better prognosis (hazard ratios, 0.68 and 0.91, respectively), said Dr. Krop, associate chief of the division of breast oncology at the Susan F. Smith Center for Women’s Cancers and clinical research director of the breast oncology center at Dana-Farber Cancer Institute, both in Boston.
TILs also suggested better outcomes (HR, 0.91), and HER2 copy number of six or greater versus lower levels of HER2 copy number was also associated with better prognosis (HR, 0.68), he noted.
Conversely, PI3K/PTEN/AKT gene alterations and MYC and ZNF703 amplification each were associated with worse outcomes (HRs, 1.35, 1.61, and 1.62, respectively).
As for predictive value, no significant association was seen between any of the amplification events and benefit of pertuzumab, nor was an interaction seen between the three-gene signature and pertuzumab benefit, Dr. Krop said.
“But if you look at the individual genes and ... the highest quartiles of expression of these genes – particularly interferon gamma and CXCL9 – it did appear that there was a statistically significant improvement in the benefit of pertuzumab if you had the highest levels of these genes, compared to lower levels of these genes,” he added.
The hazard ratios for CXCL9 of 0%-75% and greater than 75%, for example, were 0.95 and 0.49, respectively.
The interaction P values for IFNG and CXCL9 were statistically significant, but a trend toward benefit with PD-L1 did not reach statistical significance, Dr. Krop noted.
As with IFNG and CXCL9, the highest quartiles of TILs also predicted greater pertuzumab benefit (HRs for TILs at 0-75% and greater than 75%, 0.95 and 0.35, respectively), and the association was highly significant (P = .003).
HER2 copy number of six or greater was also associated with significantly greater benefit with pertuzumab (HRs for copy number of six or greater vs. less than six, 0.75 and 1.41, respectively).
A trend was seen toward decreased benefit of pertuzumab in patients with P13K/PTEN/AKT alteration, but this was not statistically significant, he noted.
However, the trend, coupled with the poor prognosis found to be associated with P13K-altered cancers, “would suggest that we need to identify new therapies – alternative approaches – to maximize treatment benefit in this cancer subtype,” he said.
“This biomarker analysis is possibly the largest and most comprehensive to date in HER2-positive breast cancer,” Dr. Krop said, noting that the findings provide support for an immune-mediated mechanism of action for pertuzumab, and suggest a need for alternative therapies for patients with low levels of TILs or immune gene markers in order to maximize their outcomes.
“We hope these data will be useful to refine future trials of early-stage HER2-positive breast cancer,” he said.
Dr. Krop reported relationships – including employment, leadership, and stock ownership – with AMAG, as well as honoraria from Genentech/Roche; consulting or advisory roles with Context Therapeutics, Daiichi Sankyo, Genentech/Roche, MacroGenics, Seattle Genetics, and Taiho Pharmaceutical; and research funding from Genentech and Pfizer to his institution.
SOURCE: Krop IE et al. ASCO 2019, Abstract 1012 .
REPORTING FROM ASCO 2019