HONOLULU – Treatment with the pan-HER tyrosine kinase inhibitor neratinib leads to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, preliminary efficacy results from the phase 2 SUMMIT basket trial suggest.

Of 11 trial subjects evaluable for efficacy, 3 (27%) had objective confirmed responses and 6 others had stable disease for at least 16 weeks (clinical benefit rate, 55%). Median progression-free survival was 7 months, Anishka D’Souza, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Study subjects included HER2-mutant metastatic cervical cancer patients. Most (89%) had adenocarcinoma and 11% had squamous cell carcinoma, said Dr. D’Souza of the University of Southern California, Los Angeles.

The median number of total prior regimens was two, with a range of one to four, she said. Patients received oral neratinib at a dose of 240 mg once daily.

The treatment was generally well tolerated; the most common adverse event was diarrhea, with only one grade 3/4 case occurring, she said, noting that high-dose loperamide prophylaxis was mandatory during cycle 1 because of the high incidence of diarrhea.

Though preliminary, the findings are notable as somatic HER2 (ERBB2) mutations, observed in about 5% of metastatic cervical cancer cases, are associated with poor prognosis, she explained, noting that there are limited treatment options and few long-term durable responses.

“There is a great need for additional treatment options,” she said.

Neratinib has been shown to have single-agent clinical activity in multiple HER2‑mutant cancers, so Dr. D’Souza and her colleagues are assessing its safety and efficacy as either monotherapy or in combination with other treatments across multiple tumor types. The current analysis focuses on the cohort of patients who received neratinib monotherapy.

Neratinib use in this cohort led to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, she said, adding that “this is an ongoing study and we are continuing to enroll patients to expand our dataset.”

Dr. D’Souza reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: D’Souza A et al. SGO 2019, Abstract 18.

HONOLULU – Treatment with the pan-HER tyrosine kinase inhibitor neratinib leads to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, preliminary efficacy results from the phase 2 SUMMIT basket trial suggest.

Of 11 trial subjects evaluable for efficacy, 3 (27%) had objective confirmed responses and 6 others had stable disease for at least 16 weeks (clinical benefit rate, 55%). Median progression-free survival was 7 months, Anishka D’Souza, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Study subjects included HER2-mutant metastatic cervical cancer patients. Most (89%) had adenocarcinoma and 11% had squamous cell carcinoma, said Dr. D’Souza of the University of Southern California, Los Angeles.

The median number of total prior regimens was two, with a range of one to four, she said. Patients received oral neratinib at a dose of 240 mg once daily.

The treatment was generally well tolerated; the most common adverse event was diarrhea, with only one grade 3/4 case occurring, she said, noting that high-dose loperamide prophylaxis was mandatory during cycle 1 because of the high incidence of diarrhea.

Though preliminary, the findings are notable as somatic HER2 (ERBB2) mutations, observed in about 5% of metastatic cervical cancer cases, are associated with poor prognosis, she explained, noting that there are limited treatment options and few long-term durable responses.

“There is a great need for additional treatment options,” she said.

Neratinib has been shown to have single-agent clinical activity in multiple HER2‑mutant cancers, so Dr. D’Souza and her colleagues are assessing its safety and efficacy as either monotherapy or in combination with other treatments across multiple tumor types. The current analysis focuses on the cohort of patients who received neratinib monotherapy.

Neratinib use in this cohort led to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, she said, adding that “this is an ongoing study and we are continuing to enroll patients to expand our dataset.”

Dr. D’Souza reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: D’Souza A et al. SGO 2019, Abstract 18.

HONOLULU – Treatment with the pan-HER tyrosine kinase inhibitor neratinib leads to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, preliminary efficacy results from the phase 2 SUMMIT basket trial suggest.

Of 11 trial subjects evaluable for efficacy, 3 (27%) had objective confirmed responses and 6 others had stable disease for at least 16 weeks (clinical benefit rate, 55%). Median progression-free survival was 7 months, Anishka D’Souza, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Study subjects included HER2-mutant metastatic cervical cancer patients. Most (89%) had adenocarcinoma and 11% had squamous cell carcinoma, said Dr. D’Souza of the University of Southern California, Los Angeles.

The median number of total prior regimens was two, with a range of one to four, she said. Patients received oral neratinib at a dose of 240 mg once daily.

The treatment was generally well tolerated; the most common adverse event was diarrhea, with only one grade 3/4 case occurring, she said, noting that high-dose loperamide prophylaxis was mandatory during cycle 1 because of the high incidence of diarrhea.

Though preliminary, the findings are notable as somatic HER2 (ERBB2) mutations, observed in about 5% of metastatic cervical cancer cases, are associated with poor prognosis, she explained, noting that there are limited treatment options and few long-term durable responses.

“There is a great need for additional treatment options,” she said.

Neratinib has been shown to have single-agent clinical activity in multiple HER2‑mutant cancers, so Dr. D’Souza and her colleagues are assessing its safety and efficacy as either monotherapy or in combination with other treatments across multiple tumor types. The current analysis focuses on the cohort of patients who received neratinib monotherapy.

Neratinib use in this cohort led to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, she said, adding that “this is an ongoing study and we are continuing to enroll patients to expand our dataset.”

Dr. D’Souza reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: D’Souza A et al. SGO 2019, Abstract 18.

HONOLULU – The perceived risk of HPV-related cancer appears to overcome variables that typically impede access to HPV vaccination, according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

An analysis showed that adolescents in Alabama are more likely to receive the HPV vaccine if they live below the poverty line and reside in rural areas. The study also revealed a positive association between vaccine uptake and the incidence of HPV-related cancer by county.

These results suggest the perceived risk of HPV-related cancer may outweigh rurality and poverty—factors that might otherwise hinder access to health care, according to Jennifer Y. Pierce, MD, of Mitchell Cancer Institute in Mobile, Ala.

She discussed this idea when presenting the study results at the meeting.

“There are 39,000 preventable cases of HPV-related cancer in the United States,” Dr. Pierce said. “In Alabama, we are [ranked] third for cervical cancer incidence and first for cervical cancer mortality. When we look at vaccination rates in Alabama, unfortunately, we have the opposite problem. We are 45th for HPV vaccination.”

Dr. Pierce also noted that, nationally, adolescents in rural areas are 11% less likely to be vaccinated than their peers in urban areas.

“When we looked in Alabama, that did not exist,” Dr. Pierce said. “So we wanted to know, ‘What are the factors associated with HPV vaccination rate, by county, in the state of Alabama?’ because we had widely disparate rates by county.”

Dr. Pierce and her colleagues looked at data from the U.S. census, county health rankings for Alabama, the Alabama state cancer registry, and other sources. The researchers wanted to determine rates of HPV vaccination in 13- to 17-year-olds as well as rates of HPV-related cancers and variables associated with HPV vaccination by county.

Dr. Pierce said that, of the 67 counties in Alabama, 50%-70% of them are rural. Forty of them have a higher percent poverty level than the state mean. Twenty-three counties have no pediatrician, and four counties have no vaccine provider other than the health department.

By county, cancer rates were positively associated with HPV vaccination in both sexes. Higher cervical cancer rates correlated with higher HPV vaccination rates in females (r = .49; P = .011) and males (r = .46; P = .017). Higher HPV-related cancer rates in males correlated with higher HPV vaccination rates in females (r = .49; P = .001) and males (r = .46; P = .001).

The researchers found no significant association between vaccine uptake and the primary care provider ratio or the number of pediatricians per county. However, private insurance (r = –.40; P = .001) and higher median household income (r = –.40; P = .0007) were associated with lower HPV vaccine uptake. Rurality (r = .27; P = .025) and having a higher percentage of people below the poverty line (r = .39; P = .0011) were associated with higher vaccine uptake.

“How do we explain this paradox?” Dr. Pierce asked. “I think, really, it speaks to the strong commitment of our county public health departments who have, for a long time, been pushing the HPV vaccine and are doing a fairly good job of vaccinating. But I think, even more so, we need to focus on this question of perceived risk.”

“Our poor, rural adolescents in Alabama are being vaccinated at a higher rate than their more affluent peers, and those HPV vaccination rates appear to be directly linked to the cancer incidence rates in those counties.”

Dr. Pierce had no disclosures.

jensmith@mdedge.com

SOURCE: Pierce JY et al. SGO 2019, Abstract 13.

HONOLULU – The perceived risk of HPV-related cancer appears to overcome variables that typically impede access to HPV vaccination, according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

An analysis showed that adolescents in Alabama are more likely to receive the HPV vaccine if they live below the poverty line and reside in rural areas. The study also revealed a positive association between vaccine uptake and the incidence of HPV-related cancer by county.

These results suggest the perceived risk of HPV-related cancer may outweigh rurality and poverty—factors that might otherwise hinder access to health care, according to Jennifer Y. Pierce, MD, of Mitchell Cancer Institute in Mobile, Ala.

She discussed this idea when presenting the study results at the meeting.

“There are 39,000 preventable cases of HPV-related cancer in the United States,” Dr. Pierce said. “In Alabama, we are [ranked] third for cervical cancer incidence and first for cervical cancer mortality. When we look at vaccination rates in Alabama, unfortunately, we have the opposite problem. We are 45th for HPV vaccination.”

Dr. Pierce also noted that, nationally, adolescents in rural areas are 11% less likely to be vaccinated than their peers in urban areas.

“When we looked in Alabama, that did not exist,” Dr. Pierce said. “So we wanted to know, ‘What are the factors associated with HPV vaccination rate, by county, in the state of Alabama?’ because we had widely disparate rates by county.”

Dr. Pierce and her colleagues looked at data from the U.S. census, county health rankings for Alabama, the Alabama state cancer registry, and other sources. The researchers wanted to determine rates of HPV vaccination in 13- to 17-year-olds as well as rates of HPV-related cancers and variables associated with HPV vaccination by county.

Dr. Pierce said that, of the 67 counties in Alabama, 50%-70% of them are rural. Forty of them have a higher percent poverty level than the state mean. Twenty-three counties have no pediatrician, and four counties have no vaccine provider other than the health department.

By county, cancer rates were positively associated with HPV vaccination in both sexes. Higher cervical cancer rates correlated with higher HPV vaccination rates in females (r = .49; P = .011) and males (r = .46; P = .017). Higher HPV-related cancer rates in males correlated with higher HPV vaccination rates in females (r = .49; P = .001) and males (r = .46; P = .001).

The researchers found no significant association between vaccine uptake and the primary care provider ratio or the number of pediatricians per county. However, private insurance (r = –.40; P = .001) and higher median household income (r = –.40; P = .0007) were associated with lower HPV vaccine uptake. Rurality (r = .27; P = .025) and having a higher percentage of people below the poverty line (r = .39; P = .0011) were associated with higher vaccine uptake.

“How do we explain this paradox?” Dr. Pierce asked. “I think, really, it speaks to the strong commitment of our county public health departments who have, for a long time, been pushing the HPV vaccine and are doing a fairly good job of vaccinating. But I think, even more so, we need to focus on this question of perceived risk.”

“Our poor, rural adolescents in Alabama are being vaccinated at a higher rate than their more affluent peers, and those HPV vaccination rates appear to be directly linked to the cancer incidence rates in those counties.”

Dr. Pierce had no disclosures.

jensmith@mdedge.com

SOURCE: Pierce JY et al. SGO 2019, Abstract 13.

HONOLULU – The perceived risk of HPV-related cancer appears to overcome variables that typically impede access to HPV vaccination, according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

An analysis showed that adolescents in Alabama are more likely to receive the HPV vaccine if they live below the poverty line and reside in rural areas. The study also revealed a positive association between vaccine uptake and the incidence of HPV-related cancer by county.

These results suggest the perceived risk of HPV-related cancer may outweigh rurality and poverty—factors that might otherwise hinder access to health care, according to Jennifer Y. Pierce, MD, of Mitchell Cancer Institute in Mobile, Ala.

She discussed this idea when presenting the study results at the meeting.

“There are 39,000 preventable cases of HPV-related cancer in the United States,” Dr. Pierce said. “In Alabama, we are [ranked] third for cervical cancer incidence and first for cervical cancer mortality. When we look at vaccination rates in Alabama, unfortunately, we have the opposite problem. We are 45th for HPV vaccination.”

Dr. Pierce also noted that, nationally, adolescents in rural areas are 11% less likely to be vaccinated than their peers in urban areas.

“When we looked in Alabama, that did not exist,” Dr. Pierce said. “So we wanted to know, ‘What are the factors associated with HPV vaccination rate, by county, in the state of Alabama?’ because we had widely disparate rates by county.”

Dr. Pierce and her colleagues looked at data from the U.S. census, county health rankings for Alabama, the Alabama state cancer registry, and other sources. The researchers wanted to determine rates of HPV vaccination in 13- to 17-year-olds as well as rates of HPV-related cancers and variables associated with HPV vaccination by county.

Dr. Pierce said that, of the 67 counties in Alabama, 50%-70% of them are rural. Forty of them have a higher percent poverty level than the state mean. Twenty-three counties have no pediatrician, and four counties have no vaccine provider other than the health department.

By county, cancer rates were positively associated with HPV vaccination in both sexes. Higher cervical cancer rates correlated with higher HPV vaccination rates in females (r = .49; P = .011) and males (r = .46; P = .017). Higher HPV-related cancer rates in males correlated with higher HPV vaccination rates in females (r = .49; P = .001) and males (r = .46; P = .001).

The researchers found no significant association between vaccine uptake and the primary care provider ratio or the number of pediatricians per county. However, private insurance (r = –.40; P = .001) and higher median household income (r = –.40; P = .0007) were associated with lower HPV vaccine uptake. Rurality (r = .27; P = .025) and having a higher percentage of people below the poverty line (r = .39; P = .0011) were associated with higher vaccine uptake.

“How do we explain this paradox?” Dr. Pierce asked. “I think, really, it speaks to the strong commitment of our county public health departments who have, for a long time, been pushing the HPV vaccine and are doing a fairly good job of vaccinating. But I think, even more so, we need to focus on this question of perceived risk.”

“Our poor, rural adolescents in Alabama are being vaccinated at a higher rate than their more affluent peers, and those HPV vaccination rates appear to be directly linked to the cancer incidence rates in those counties.”

Dr. Pierce had no disclosures.

jensmith@mdedge.com

SOURCE: Pierce JY et al. SGO 2019, Abstract 13.

HONOLULU – Women at high risk for ovarian cancer who undergo risk-reducing salpingo-oophorectomy (RRSO) or interval salpingectomy with delayed oophorectomy (ISDO) experience significant reductions in cancer distress, according to preliminary findings from the WISP (Women Choosing Surgical Prevention) study.

Sharon Worcester/MDedge News

However, those who choose RRSO experience worse menopausal symptoms and higher rates of regret, Karen H. Lu, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. Of 183 women enrolled to date in the prospective, nonrandomized, multicenter study, 91 underwent RRSO and 92 underwent ISDO at a median age of 40.9 and 37.5 years, respectively. Significant decreases in cancer-related distress as measured using the Impact of Event scale were seen in both groups at 6-month follow-up after surgery: The mean scores in the RRSO arm were 19.6 at baseline and 10.9 at 6 months, and in the ISDO arm they were 20.8 and 14.0, respectively.

The decrease in scores at 6 months did not differ significantly between study arms, but women in the RRSO arm had a significantly increased incidence of hot flashes, night sweats, vaginal dryness, and weight gain after surgery, said Dr. Lu, professor and chair in the department of gynecologic oncology and reproductive medicine and the J. Taylor Wharton Distinguished Chair in Gynecologic Oncology at the University of Texas MD Anderson Cancer Center, Houston.

“There was a significant difference in quality of life physical scores in RRSO versus the salpingectomy arm,” she said, adding that no difference was seen between the groups in quality of life mental scores.

The level of decision regret was significantly higher in the women who underwent RRSO (scores,14.1 vs. 8.7 on the 100-point scale), she noted.

“We hypothesized that use of HRT [hormone replacement therapy] after RRSO may have accounted for this difference, and looked at the two subsets,” she said. “Within the RRSO group, 25% did not go on HRT, and while higher than ISDO scores, these scores did not account for the large difference in decision regret.”

About half of the women had a history of breast cancer.

“Clinically, this agrees with what we see in that women with a prior history of breast cancer have less angst about undergoing RRSO,” she said, adding that 75% of women in the RRSO arm did go on HRT, and “these women represent the majority of our ‘previvors’ – healthy women with no history of cancer who struggle with the RRSO decision and who are able to take HRT.”

“Interestingly, compared to ISDO, RRSO women on HRT had the highest decisional regret,” she said.

An analysis of numerous possible predictors of decisional regret showed that only baseline depression score was a significant independent predictor, she noted.

Study participants are premenopausal women aged 30-50 years who have a high risk of ovarian cancer because of a pathogenic germline mutation in an ovarian cancer predisposition gene, and a normal CA125 and transvaginal ultrasound within 6 months before enrollment. All receive scripted counseling about the recommended age for oophorectomy and can choose their study arm. Planned enrollment at nine participating U.S. centers is 270 women.

The RRSO and ISDO arms at current enrollment are statistically similar with respect to mutation type, education level, breast cancer history, and first/second-degree ovarian cancer, but significantly more women in the ISDO arm had undergone risk-reducing mastectomy (51% vs. 35%), Dr. Lu noted, adding that to date no ovarian cancers have been identified at initial surgery, between surgeries, or at the time of completion oophorectomy in the ISDO patients – although only two women in that arm have undergone completion oophorectomy.

In the RRSO arm, one high-grade serous tubal intraepithelial neoplasia (STIC) was found at the time of surgery in a PALB2 mutation carrier.

“We believe this is the first report of a STIC in a PALB2 carrier. This woman was 39 years old with a strong family history of breast and ovarian cancer,” she said.

The findings suggest that “for these high-risk women who underwent ISDO ... the option encouraged them to undergo limited but potentially lifesaving surgical prophylaxis at an earlier age rather than wait to undergo full surgical prophylaxis at the upper-accepted age limit due to fear of early menopause,” Dr. Lu said.

Safety continues to be closely monitored in this study and the use of ISDO outside of the clinical trial setting is not recommended, she added, noting that an expansion of both WISP and the TUBA trial, for which preliminary results showing similar outcomes were also presented at the SGO meeting, is planned.

Dr. Lu reported having no disclosures.

sworcester@mdedge.com

SOURCE: Lu KH et al. SGO 2019, Late-Breaking Abstract 3.

HONOLULU – Women at high risk for ovarian cancer who undergo risk-reducing salpingo-oophorectomy (RRSO) or interval salpingectomy with delayed oophorectomy (ISDO) experience significant reductions in cancer distress, according to preliminary findings from the WISP (Women Choosing Surgical Prevention) study.

Sharon Worcester/MDedge News

However, those who choose RRSO experience worse menopausal symptoms and higher rates of regret, Karen H. Lu, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. Of 183 women enrolled to date in the prospective, nonrandomized, multicenter study, 91 underwent RRSO and 92 underwent ISDO at a median age of 40.9 and 37.5 years, respectively. Significant decreases in cancer-related distress as measured using the Impact of Event scale were seen in both groups at 6-month follow-up after surgery: The mean scores in the RRSO arm were 19.6 at baseline and 10.9 at 6 months, and in the ISDO arm they were 20.8 and 14.0, respectively.

The decrease in scores at 6 months did not differ significantly between study arms, but women in the RRSO arm had a significantly increased incidence of hot flashes, night sweats, vaginal dryness, and weight gain after surgery, said Dr. Lu, professor and chair in the department of gynecologic oncology and reproductive medicine and the J. Taylor Wharton Distinguished Chair in Gynecologic Oncology at the University of Texas MD Anderson Cancer Center, Houston.

“There was a significant difference in quality of life physical scores in RRSO versus the salpingectomy arm,” she said, adding that no difference was seen between the groups in quality of life mental scores.

The level of decision regret was significantly higher in the women who underwent RRSO (scores,14.1 vs. 8.7 on the 100-point scale), she noted.

“We hypothesized that use of HRT [hormone replacement therapy] after RRSO may have accounted for this difference, and looked at the two subsets,” she said. “Within the RRSO group, 25% did not go on HRT, and while higher than ISDO scores, these scores did not account for the large difference in decision regret.”

About half of the women had a history of breast cancer.

“Clinically, this agrees with what we see in that women with a prior history of breast cancer have less angst about undergoing RRSO,” she said, adding that 75% of women in the RRSO arm did go on HRT, and “these women represent the majority of our ‘previvors’ – healthy women with no history of cancer who struggle with the RRSO decision and who are able to take HRT.”

“Interestingly, compared to ISDO, RRSO women on HRT had the highest decisional regret,” she said.

An analysis of numerous possible predictors of decisional regret showed that only baseline depression score was a significant independent predictor, she noted.

Study participants are premenopausal women aged 30-50 years who have a high risk of ovarian cancer because of a pathogenic germline mutation in an ovarian cancer predisposition gene, and a normal CA125 and transvaginal ultrasound within 6 months before enrollment. All receive scripted counseling about the recommended age for oophorectomy and can choose their study arm. Planned enrollment at nine participating U.S. centers is 270 women.

The RRSO and ISDO arms at current enrollment are statistically similar with respect to mutation type, education level, breast cancer history, and first/second-degree ovarian cancer, but significantly more women in the ISDO arm had undergone risk-reducing mastectomy (51% vs. 35%), Dr. Lu noted, adding that to date no ovarian cancers have been identified at initial surgery, between surgeries, or at the time of completion oophorectomy in the ISDO patients – although only two women in that arm have undergone completion oophorectomy.

In the RRSO arm, one high-grade serous tubal intraepithelial neoplasia (STIC) was found at the time of surgery in a PALB2 mutation carrier.

“We believe this is the first report of a STIC in a PALB2 carrier. This woman was 39 years old with a strong family history of breast and ovarian cancer,” she said.

The findings suggest that “for these high-risk women who underwent ISDO ... the option encouraged them to undergo limited but potentially lifesaving surgical prophylaxis at an earlier age rather than wait to undergo full surgical prophylaxis at the upper-accepted age limit due to fear of early menopause,” Dr. Lu said.

Safety continues to be closely monitored in this study and the use of ISDO outside of the clinical trial setting is not recommended, she added, noting that an expansion of both WISP and the TUBA trial, for which preliminary results showing similar outcomes were also presented at the SGO meeting, is planned.

Dr. Lu reported having no disclosures.

sworcester@mdedge.com

SOURCE: Lu KH et al. SGO 2019, Late-Breaking Abstract 3.

HONOLULU – Women at high risk for ovarian cancer who undergo risk-reducing salpingo-oophorectomy (RRSO) or interval salpingectomy with delayed oophorectomy (ISDO) experience significant reductions in cancer distress, according to preliminary findings from the WISP (Women Choosing Surgical Prevention) study.

Sharon Worcester/MDedge News

However, those who choose RRSO experience worse menopausal symptoms and higher rates of regret, Karen H. Lu, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. Of 183 women enrolled to date in the prospective, nonrandomized, multicenter study, 91 underwent RRSO and 92 underwent ISDO at a median age of 40.9 and 37.5 years, respectively. Significant decreases in cancer-related distress as measured using the Impact of Event scale were seen in both groups at 6-month follow-up after surgery: The mean scores in the RRSO arm were 19.6 at baseline and 10.9 at 6 months, and in the ISDO arm they were 20.8 and 14.0, respectively.

The decrease in scores at 6 months did not differ significantly between study arms, but women in the RRSO arm had a significantly increased incidence of hot flashes, night sweats, vaginal dryness, and weight gain after surgery, said Dr. Lu, professor and chair in the department of gynecologic oncology and reproductive medicine and the J. Taylor Wharton Distinguished Chair in Gynecologic Oncology at the University of Texas MD Anderson Cancer Center, Houston.

“There was a significant difference in quality of life physical scores in RRSO versus the salpingectomy arm,” she said, adding that no difference was seen between the groups in quality of life mental scores.

The level of decision regret was significantly higher in the women who underwent RRSO (scores,14.1 vs. 8.7 on the 100-point scale), she noted.

“We hypothesized that use of HRT [hormone replacement therapy] after RRSO may have accounted for this difference, and looked at the two subsets,” she said. “Within the RRSO group, 25% did not go on HRT, and while higher than ISDO scores, these scores did not account for the large difference in decision regret.”

About half of the women had a history of breast cancer.

“Clinically, this agrees with what we see in that women with a prior history of breast cancer have less angst about undergoing RRSO,” she said, adding that 75% of women in the RRSO arm did go on HRT, and “these women represent the majority of our ‘previvors’ – healthy women with no history of cancer who struggle with the RRSO decision and who are able to take HRT.”

“Interestingly, compared to ISDO, RRSO women on HRT had the highest decisional regret,” she said.

An analysis of numerous possible predictors of decisional regret showed that only baseline depression score was a significant independent predictor, she noted.

Study participants are premenopausal women aged 30-50 years who have a high risk of ovarian cancer because of a pathogenic germline mutation in an ovarian cancer predisposition gene, and a normal CA125 and transvaginal ultrasound within 6 months before enrollment. All receive scripted counseling about the recommended age for oophorectomy and can choose their study arm. Planned enrollment at nine participating U.S. centers is 270 women.

The RRSO and ISDO arms at current enrollment are statistically similar with respect to mutation type, education level, breast cancer history, and first/second-degree ovarian cancer, but significantly more women in the ISDO arm had undergone risk-reducing mastectomy (51% vs. 35%), Dr. Lu noted, adding that to date no ovarian cancers have been identified at initial surgery, between surgeries, or at the time of completion oophorectomy in the ISDO patients – although only two women in that arm have undergone completion oophorectomy.

In the RRSO arm, one high-grade serous tubal intraepithelial neoplasia (STIC) was found at the time of surgery in a PALB2 mutation carrier.

“We believe this is the first report of a STIC in a PALB2 carrier. This woman was 39 years old with a strong family history of breast and ovarian cancer,” she said.

The findings suggest that “for these high-risk women who underwent ISDO ... the option encouraged them to undergo limited but potentially lifesaving surgical prophylaxis at an earlier age rather than wait to undergo full surgical prophylaxis at the upper-accepted age limit due to fear of early menopause,” Dr. Lu said.

Safety continues to be closely monitored in this study and the use of ISDO outside of the clinical trial setting is not recommended, she added, noting that an expansion of both WISP and the TUBA trial, for which preliminary results showing similar outcomes were also presented at the SGO meeting, is planned.

Dr. Lu reported having no disclosures.

sworcester@mdedge.com

SOURCE: Lu KH et al. SGO 2019, Late-Breaking Abstract 3.

NEW ORLEANS – For patients with atrial fibrillation and either a recent acute coronary syndrome or percutaneous coronary intervention, combined treatment for 6 months with the anticoagulant apixaban and a P2Y12 inhibitor antiplatelet drug, but without aspirin, was safer than and as effective as a regimen that either also included aspirin or that substituted a vitamin K antagonist, such as warfarin, for the direct-acting oral anticoagulant, based on results from a multicenter, randomized trial with more than 4,600 patients.

The apixaban plus P2Y12 inhibitor (typically, clopidogrel) combination “resulted in less bleeding and fewer hospitalizations without significant differences in ischemic events than regimens that included a vitamin K antagonist, aspirin, or both,” Renato D. Lopes, MD, said at the annual meeting of the American College of Cardiology. Concurrently, his report of the results also appeared in an online article.

This finding in the AUGUSTUS trial gives clinicians more guidance for the long-standing dilemma of how to best prevent arterial thrombus formation in patients with atrial fibrillation (AFib). To prevent a stroke, these patients routinely receive treatment with an anticoagulant when they have an acute coronary syndrome (ACS) event or undergo percutaneous coronary intervention (PCI). Typically, they receive several months of dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor to prevent a clot from forming in the stented or unstable region of a coronary artery.

These patients are not uncommon; this circumstance occurs for about 20% of all AFib patients, and poses the question of what is the safest and most effective way to treat them. Should they get triple therapy with an anticoagulant, aspirin, and a P2Y12 inhibitor, an option that could cause excess bleeding; or should one of the three drugs drop out with the potential for an increased rate of ischemic events? The AUGUSTUS findings suggest that one solution is treatment with a combination of the direct-acting oral anticoagulant apixaban (Eliquis) and the P2Y12 inhibitor clopidogrel (Plavix) but without aspirin.

For the majority of patients like the ones enrolled, “less is more.” By dropping aspirin from the treatment mix, patients did better, said Dr. Lopes, a professor of medicine at Duke University in Durham, N.C.

Dr. Lopes and his associates designed AUGUSTUS (A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis [Blood Clots] Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart) as a two-by-two factorial study to address two different questions: During 6 months of treatment, how did apixaban compare with a vitamin K antagonist (usually warfarin) in these patients for safety and efficacy, and how did aspirin compare with placebo in this setting for the same endpoints?

The trial enrolled 4,614 patients at 492 sites in 33 countries. All patients in the study received a P2Y12 inhibitor, with 93% treated with clopidogrel. The study had roughly as many patients as the combined total of patients enrolled in two smaller, prior studies that had looked at roughly the same questions in similar patients.

“The aspirin part is the more interesting, and probably more unique and important finding,” John H. Alexander, MD, a coinvestigator on the study, said in a video interview. Regardless of the anticoagulant used, patients who received aspirin had a 16% rate of major bleeds or clinically relevant non-major bleeds, compared with a 9% rate among those on placebo, a statistically significant result that underscored the bleeding risk posed by adding aspirin to an anticoagulant and a P2Y12 inhibitor.

The results also showed no statistically significant difference in any efficacy measure with or without aspirin, including the rate of death or hospitalization, or of any individual ischemic endpoint. However the results showed a signal of a small increase in the rates of each of three types of ischemic events – stent thrombosis, MI, and need for urgent revascularization, each of which showed a numerical increase when aspirin was dropped. But the increase was small.

Dr. Lopes calculated that, for example, to prevent one episode of stent thrombosis by treating with aspirin also would cause 15 major or clinically relevant non-major bleeds, which makes inclusion of aspirin something of a judgment call for each patient, said Dr. Alexander, a professor of medicine at Duke. An AFib patient with a high risk for thrombosis but a low risk for bleeding following PCI or an ACS event might be a reasonable patient to treat with aspirin along with apixaban and a P2Y12 inhibitor, he explained.

The rate of major or clinically relevant bleeds was 11% with apixaban and 15% with a vitamin K antagonist, a statistically significant difference. Patients treated with apixaban also had a significantly reduced rate of death or hospitalization, 24%, compared with 27% among those on the vitamin K antagonist, as well as a significantly lower rate of stroke.

Overall the lowest bleeding rate was in patients on apixaban but no aspirin, a 7% rate, while the highest rate was in patients on a vitamin K antagonist plus aspirin, a 19% rate.

Dr. Alexander said that it would be an overreach to extrapolate these findings to other direct-acting oral anticoagulants, compared with a vitamin K antagonist, but he believed that the findings the study generated about aspirin were probably relevant regardless of the anticoagulant used.
 

mzoler@mdedge.com

On Twitter @mitchelzoler

NEW ORLEANS – For patients with atrial fibrillation and either a recent acute coronary syndrome or percutaneous coronary intervention, combined treatment for 6 months with the anticoagulant apixaban and a P2Y12 inhibitor antiplatelet drug, but without aspirin, was safer than and as effective as a regimen that either also included aspirin or that substituted a vitamin K antagonist, such as warfarin, for the direct-acting oral anticoagulant, based on results from a multicenter, randomized trial with more than 4,600 patients.

The apixaban plus P2Y12 inhibitor (typically, clopidogrel) combination “resulted in less bleeding and fewer hospitalizations without significant differences in ischemic events than regimens that included a vitamin K antagonist, aspirin, or both,” Renato D. Lopes, MD, said at the annual meeting of the American College of Cardiology. Concurrently, his report of the results also appeared in an online article.

This finding in the AUGUSTUS trial gives clinicians more guidance for the long-standing dilemma of how to best prevent arterial thrombus formation in patients with atrial fibrillation (AFib). To prevent a stroke, these patients routinely receive treatment with an anticoagulant when they have an acute coronary syndrome (ACS) event or undergo percutaneous coronary intervention (PCI). Typically, they receive several months of dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor to prevent a clot from forming in the stented or unstable region of a coronary artery.

These patients are not uncommon; this circumstance occurs for about 20% of all AFib patients, and poses the question of what is the safest and most effective way to treat them. Should they get triple therapy with an anticoagulant, aspirin, and a P2Y12 inhibitor, an option that could cause excess bleeding; or should one of the three drugs drop out with the potential for an increased rate of ischemic events? The AUGUSTUS findings suggest that one solution is treatment with a combination of the direct-acting oral anticoagulant apixaban (Eliquis) and the P2Y12 inhibitor clopidogrel (Plavix) but without aspirin.

For the majority of patients like the ones enrolled, “less is more.” By dropping aspirin from the treatment mix, patients did better, said Dr. Lopes, a professor of medicine at Duke University in Durham, N.C.

Dr. Lopes and his associates designed AUGUSTUS (A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis [Blood Clots] Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart) as a two-by-two factorial study to address two different questions: During 6 months of treatment, how did apixaban compare with a vitamin K antagonist (usually warfarin) in these patients for safety and efficacy, and how did aspirin compare with placebo in this setting for the same endpoints?

The trial enrolled 4,614 patients at 492 sites in 33 countries. All patients in the study received a P2Y12 inhibitor, with 93% treated with clopidogrel. The study had roughly as many patients as the combined total of patients enrolled in two smaller, prior studies that had looked at roughly the same questions in similar patients.

“The aspirin part is the more interesting, and probably more unique and important finding,” John H. Alexander, MD, a coinvestigator on the study, said in a video interview. Regardless of the anticoagulant used, patients who received aspirin had a 16% rate of major bleeds or clinically relevant non-major bleeds, compared with a 9% rate among those on placebo, a statistically significant result that underscored the bleeding risk posed by adding aspirin to an anticoagulant and a P2Y12 inhibitor.

The results also showed no statistically significant difference in any efficacy measure with or without aspirin, including the rate of death or hospitalization, or of any individual ischemic endpoint. However the results showed a signal of a small increase in the rates of each of three types of ischemic events – stent thrombosis, MI, and need for urgent revascularization, each of which showed a numerical increase when aspirin was dropped. But the increase was small.

Dr. Lopes calculated that, for example, to prevent one episode of stent thrombosis by treating with aspirin also would cause 15 major or clinically relevant non-major bleeds, which makes inclusion of aspirin something of a judgment call for each patient, said Dr. Alexander, a professor of medicine at Duke. An AFib patient with a high risk for thrombosis but a low risk for bleeding following PCI or an ACS event might be a reasonable patient to treat with aspirin along with apixaban and a P2Y12 inhibitor, he explained.

The rate of major or clinically relevant bleeds was 11% with apixaban and 15% with a vitamin K antagonist, a statistically significant difference. Patients treated with apixaban also had a significantly reduced rate of death or hospitalization, 24%, compared with 27% among those on the vitamin K antagonist, as well as a significantly lower rate of stroke.

Overall the lowest bleeding rate was in patients on apixaban but no aspirin, a 7% rate, while the highest rate was in patients on a vitamin K antagonist plus aspirin, a 19% rate.

Dr. Alexander said that it would be an overreach to extrapolate these findings to other direct-acting oral anticoagulants, compared with a vitamin K antagonist, but he believed that the findings the study generated about aspirin were probably relevant regardless of the anticoagulant used.
 

mzoler@mdedge.com

On Twitter @mitchelzoler

NEW ORLEANS – For patients with atrial fibrillation and either a recent acute coronary syndrome or percutaneous coronary intervention, combined treatment for 6 months with the anticoagulant apixaban and a P2Y12 inhibitor antiplatelet drug, but without aspirin, was safer than and as effective as a regimen that either also included aspirin or that substituted a vitamin K antagonist, such as warfarin, for the direct-acting oral anticoagulant, based on results from a multicenter, randomized trial with more than 4,600 patients.

The apixaban plus P2Y12 inhibitor (typically, clopidogrel) combination “resulted in less bleeding and fewer hospitalizations without significant differences in ischemic events than regimens that included a vitamin K antagonist, aspirin, or both,” Renato D. Lopes, MD, said at the annual meeting of the American College of Cardiology. Concurrently, his report of the results also appeared in an online article.

This finding in the AUGUSTUS trial gives clinicians more guidance for the long-standing dilemma of how to best prevent arterial thrombus formation in patients with atrial fibrillation (AFib). To prevent a stroke, these patients routinely receive treatment with an anticoagulant when they have an acute coronary syndrome (ACS) event or undergo percutaneous coronary intervention (PCI). Typically, they receive several months of dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor to prevent a clot from forming in the stented or unstable region of a coronary artery.

These patients are not uncommon; this circumstance occurs for about 20% of all AFib patients, and poses the question of what is the safest and most effective way to treat them. Should they get triple therapy with an anticoagulant, aspirin, and a P2Y12 inhibitor, an option that could cause excess bleeding; or should one of the three drugs drop out with the potential for an increased rate of ischemic events? The AUGUSTUS findings suggest that one solution is treatment with a combination of the direct-acting oral anticoagulant apixaban (Eliquis) and the P2Y12 inhibitor clopidogrel (Plavix) but without aspirin.

For the majority of patients like the ones enrolled, “less is more.” By dropping aspirin from the treatment mix, patients did better, said Dr. Lopes, a professor of medicine at Duke University in Durham, N.C.

Dr. Lopes and his associates designed AUGUSTUS (A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis [Blood Clots] Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart) as a two-by-two factorial study to address two different questions: During 6 months of treatment, how did apixaban compare with a vitamin K antagonist (usually warfarin) in these patients for safety and efficacy, and how did aspirin compare with placebo in this setting for the same endpoints?

The trial enrolled 4,614 patients at 492 sites in 33 countries. All patients in the study received a P2Y12 inhibitor, with 93% treated with clopidogrel. The study had roughly as many patients as the combined total of patients enrolled in two smaller, prior studies that had looked at roughly the same questions in similar patients.

“The aspirin part is the more interesting, and probably more unique and important finding,” John H. Alexander, MD, a coinvestigator on the study, said in a video interview. Regardless of the anticoagulant used, patients who received aspirin had a 16% rate of major bleeds or clinically relevant non-major bleeds, compared with a 9% rate among those on placebo, a statistically significant result that underscored the bleeding risk posed by adding aspirin to an anticoagulant and a P2Y12 inhibitor.

The results also showed no statistically significant difference in any efficacy measure with or without aspirin, including the rate of death or hospitalization, or of any individual ischemic endpoint. However the results showed a signal of a small increase in the rates of each of three types of ischemic events – stent thrombosis, MI, and need for urgent revascularization, each of which showed a numerical increase when aspirin was dropped. But the increase was small.

Dr. Lopes calculated that, for example, to prevent one episode of stent thrombosis by treating with aspirin also would cause 15 major or clinically relevant non-major bleeds, which makes inclusion of aspirin something of a judgment call for each patient, said Dr. Alexander, a professor of medicine at Duke. An AFib patient with a high risk for thrombosis but a low risk for bleeding following PCI or an ACS event might be a reasonable patient to treat with aspirin along with apixaban and a P2Y12 inhibitor, he explained.

The rate of major or clinically relevant bleeds was 11% with apixaban and 15% with a vitamin K antagonist, a statistically significant difference. Patients treated with apixaban also had a significantly reduced rate of death or hospitalization, 24%, compared with 27% among those on the vitamin K antagonist, as well as a significantly lower rate of stroke.

Overall the lowest bleeding rate was in patients on apixaban but no aspirin, a 7% rate, while the highest rate was in patients on a vitamin K antagonist plus aspirin, a 19% rate.

Dr. Alexander said that it would be an overreach to extrapolate these findings to other direct-acting oral anticoagulants, compared with a vitamin K antagonist, but he believed that the findings the study generated about aspirin were probably relevant regardless of the anticoagulant used.
 

mzoler@mdedge.com

On Twitter @mitchelzoler

Medical journals and societies are trying to figure out ways to use social media to connect with hospitalists and others interested in their subject matter, says Charlie Wray, DO, MS, lead author of a paper proposing a way they can do that: implementing a journal-sponsored club on Twitter.

“At the Journal of Hospital Medicine (JHM), we noticed that there was a large community of hospitalists on Twitter who were looking for a community to engage in hospital medicine topics,” Dr. Wray said. “We created #JHMChat to bring the hospital medicine community together on a regular basis to talk about pertinent research, medical education philosophies, and value-based care interventions. Our ultimate goal was to increase engagement, networking, and communication among this community, while highlighting the work that is being published in JHM.”

A study of #JHMChat showed that social media is a great platform for large organizations to reach out, connect, and create a community around, he added. “We were very surprised by both the Twitter metrics (i.e., number of participants and overall impressions), which showed very large dissemination numbers, in addition to the external dissemination metrics (i.e., page views and altmetrics scores), which showed that each chat basically corresponded to a release of a new issue. This could be informative to other journals as they look for ways to increase their web traffic or disseminate their work to their respective audiences.”

Dr. Wray hopes the study alerts hospitalists to the fact that there is a large and ever-growing community available within social media.

“Second, we know that careers in hospital medicine can be tough, regardless of whether you’re at a community hospital or a large academic center. Knowing that there is a community with which you can connect to is both comforting and reassuring.”
 

Reference

Wray C et al. The adoption of an online journal club to improve research dissemination and social media engagement among hospitalists. J Hosp Med. 2018 Nov;13(11):764-9.

Medical journals and societies are trying to figure out ways to use social media to connect with hospitalists and others interested in their subject matter, says Charlie Wray, DO, MS, lead author of a paper proposing a way they can do that: implementing a journal-sponsored club on Twitter.

“At the Journal of Hospital Medicine (JHM), we noticed that there was a large community of hospitalists on Twitter who were looking for a community to engage in hospital medicine topics,” Dr. Wray said. “We created #JHMChat to bring the hospital medicine community together on a regular basis to talk about pertinent research, medical education philosophies, and value-based care interventions. Our ultimate goal was to increase engagement, networking, and communication among this community, while highlighting the work that is being published in JHM.”

A study of #JHMChat showed that social media is a great platform for large organizations to reach out, connect, and create a community around, he added. “We were very surprised by both the Twitter metrics (i.e., number of participants and overall impressions), which showed very large dissemination numbers, in addition to the external dissemination metrics (i.e., page views and altmetrics scores), which showed that each chat basically corresponded to a release of a new issue. This could be informative to other journals as they look for ways to increase their web traffic or disseminate their work to their respective audiences.”

Dr. Wray hopes the study alerts hospitalists to the fact that there is a large and ever-growing community available within social media.

“Second, we know that careers in hospital medicine can be tough, regardless of whether you’re at a community hospital or a large academic center. Knowing that there is a community with which you can connect to is both comforting and reassuring.”
 

Reference

Wray C et al. The adoption of an online journal club to improve research dissemination and social media engagement among hospitalists. J Hosp Med. 2018 Nov;13(11):764-9.

Medical journals and societies are trying to figure out ways to use social media to connect with hospitalists and others interested in their subject matter, says Charlie Wray, DO, MS, lead author of a paper proposing a way they can do that: implementing a journal-sponsored club on Twitter.

“At the Journal of Hospital Medicine (JHM), we noticed that there was a large community of hospitalists on Twitter who were looking for a community to engage in hospital medicine topics,” Dr. Wray said. “We created #JHMChat to bring the hospital medicine community together on a regular basis to talk about pertinent research, medical education philosophies, and value-based care interventions. Our ultimate goal was to increase engagement, networking, and communication among this community, while highlighting the work that is being published in JHM.”

A study of #JHMChat showed that social media is a great platform for large organizations to reach out, connect, and create a community around, he added. “We were very surprised by both the Twitter metrics (i.e., number of participants and overall impressions), which showed very large dissemination numbers, in addition to the external dissemination metrics (i.e., page views and altmetrics scores), which showed that each chat basically corresponded to a release of a new issue. This could be informative to other journals as they look for ways to increase their web traffic or disseminate their work to their respective audiences.”

Dr. Wray hopes the study alerts hospitalists to the fact that there is a large and ever-growing community available within social media.

“Second, we know that careers in hospital medicine can be tough, regardless of whether you’re at a community hospital or a large academic center. Knowing that there is a community with which you can connect to is both comforting and reassuring.”
 

Reference

Wray C et al. The adoption of an online journal club to improve research dissemination and social media engagement among hospitalists. J Hosp Med. 2018 Nov;13(11):764-9.

HONOLULU – Pembrolizumab plus bevacizumab and oral metronomic cyclophosphamide can be effective in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, a phase 2 trial suggests.

The tumor response rate observed with the three-drug regimen (40%) was better than response rates previously reported for pembrolizumab monotherapy (8%) and bevacizumab plus cyclophosphamide (24%), according to Emese Zsiros, MD, PhD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

The combination proved “very safe” and was associated with “excellent quality of life,” she said at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Dr. Zsiros and her colleagues enrolled 40 patients on a phase 2 trial (NCT02853318) of pembrolizumab, bevacizumab, and oral cyclophosphamide in recurrent, advanced-stage epithelial ovarian, fallopian tube, or primary peritoneal cancer. The trial had a safety lead-in cohort of five patients.

At baseline, the mean patient age was 62.2 years (range, 44.9-88.7 years). Most patients (82.5%, n = 33) had high-grade serous histology. The patients had received a mean of 3.2 (range, 1-12) prior lines of chemotherapy. Most patients (75%, n = 30) were platinum resistant, but 10 patients (25%) were platinum sensitive and declined platinum-based therapy.

Study treatment consisted of IV pembrolizumab at 200 mg plus IV bevacizumab at 15 mg/kg every 3 weeks and oral cyclophosphamide at 50 mg every day. Patients were treated until disease progression or unacceptable toxicity.

Results

“The triple regimen was, overall, really well tolerated,” Dr. Zsiros said.

The most common grade 1/2 treatment-related adverse events (AEs) were fatigue (n = 14), diarrhea (n = 13), nausea (n = 9), hypertension (n =7), white blood cell decrease (n = 6), and arthralgia (n = 6).

Grade 3 related AEs included hypertension (n = 5), lymphocyte count decrease (n = 3), and white blood cell decrease (n = 1). There was one grade 4 drug-related AE of decreased lymphocyte count.

The overall response rate was 40%, with all 16 responders having a partial response. The rate of stable disease was 55% (n = 22).

“Only 2 patients out of the 40 progressed after initiation of the treatment, and I would like to point out that both of these patients had a very large disease burden,” Dr. Zsiros said.

She also noted that more than 77% of patients had a decrease in tumor size from baseline.

The disease control rate (partial response plus stable disease) was 95.0% (n = 38) initially and 62.5% (n = 25) at 6 months. However, three patients had not yet reached 6 months follow-up at the data cutoff.

“I would like to point out that 30% of the patients [n = 12] derived an especially long-term clinical benefit over 12 months and 12 cycles of treatment,” Dr. Zsiros said.

She added that quality of life assessment revealed “high physical, emotional, cognitive, and social functioning throughout the clinical trial.” The researchers also observed significantly improved body image from baseline (P less than .002).

Dr. Zsiros reported relationships with Iovance Biotherapeutics and AstraZeneca. The trial was sponsored by Roswell Park Cancer Institute in collaboration with the National Cancer Institute.

jensmith@mdedge.com

SOURCE: Zsiros E et al. SGO 2019, Abstract LBA4.

HONOLULU – Pembrolizumab plus bevacizumab and oral metronomic cyclophosphamide can be effective in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, a phase 2 trial suggests.

The tumor response rate observed with the three-drug regimen (40%) was better than response rates previously reported for pembrolizumab monotherapy (8%) and bevacizumab plus cyclophosphamide (24%), according to Emese Zsiros, MD, PhD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

The combination proved “very safe” and was associated with “excellent quality of life,” she said at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Dr. Zsiros and her colleagues enrolled 40 patients on a phase 2 trial (NCT02853318) of pembrolizumab, bevacizumab, and oral cyclophosphamide in recurrent, advanced-stage epithelial ovarian, fallopian tube, or primary peritoneal cancer. The trial had a safety lead-in cohort of five patients.

At baseline, the mean patient age was 62.2 years (range, 44.9-88.7 years). Most patients (82.5%, n = 33) had high-grade serous histology. The patients had received a mean of 3.2 (range, 1-12) prior lines of chemotherapy. Most patients (75%, n = 30) were platinum resistant, but 10 patients (25%) were platinum sensitive and declined platinum-based therapy.

Study treatment consisted of IV pembrolizumab at 200 mg plus IV bevacizumab at 15 mg/kg every 3 weeks and oral cyclophosphamide at 50 mg every day. Patients were treated until disease progression or unacceptable toxicity.

Results

“The triple regimen was, overall, really well tolerated,” Dr. Zsiros said.

The most common grade 1/2 treatment-related adverse events (AEs) were fatigue (n = 14), diarrhea (n = 13), nausea (n = 9), hypertension (n =7), white blood cell decrease (n = 6), and arthralgia (n = 6).

Grade 3 related AEs included hypertension (n = 5), lymphocyte count decrease (n = 3), and white blood cell decrease (n = 1). There was one grade 4 drug-related AE of decreased lymphocyte count.

The overall response rate was 40%, with all 16 responders having a partial response. The rate of stable disease was 55% (n = 22).

“Only 2 patients out of the 40 progressed after initiation of the treatment, and I would like to point out that both of these patients had a very large disease burden,” Dr. Zsiros said.

She also noted that more than 77% of patients had a decrease in tumor size from baseline.

The disease control rate (partial response plus stable disease) was 95.0% (n = 38) initially and 62.5% (n = 25) at 6 months. However, three patients had not yet reached 6 months follow-up at the data cutoff.

“I would like to point out that 30% of the patients [n = 12] derived an especially long-term clinical benefit over 12 months and 12 cycles of treatment,” Dr. Zsiros said.

She added that quality of life assessment revealed “high physical, emotional, cognitive, and social functioning throughout the clinical trial.” The researchers also observed significantly improved body image from baseline (P less than .002).

Dr. Zsiros reported relationships with Iovance Biotherapeutics and AstraZeneca. The trial was sponsored by Roswell Park Cancer Institute in collaboration with the National Cancer Institute.

jensmith@mdedge.com

SOURCE: Zsiros E et al. SGO 2019, Abstract LBA4.

HONOLULU – Pembrolizumab plus bevacizumab and oral metronomic cyclophosphamide can be effective in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, a phase 2 trial suggests.

The tumor response rate observed with the three-drug regimen (40%) was better than response rates previously reported for pembrolizumab monotherapy (8%) and bevacizumab plus cyclophosphamide (24%), according to Emese Zsiros, MD, PhD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

The combination proved “very safe” and was associated with “excellent quality of life,” she said at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Dr. Zsiros and her colleagues enrolled 40 patients on a phase 2 trial (NCT02853318) of pembrolizumab, bevacizumab, and oral cyclophosphamide in recurrent, advanced-stage epithelial ovarian, fallopian tube, or primary peritoneal cancer. The trial had a safety lead-in cohort of five patients.

At baseline, the mean patient age was 62.2 years (range, 44.9-88.7 years). Most patients (82.5%, n = 33) had high-grade serous histology. The patients had received a mean of 3.2 (range, 1-12) prior lines of chemotherapy. Most patients (75%, n = 30) were platinum resistant, but 10 patients (25%) were platinum sensitive and declined platinum-based therapy.

Study treatment consisted of IV pembrolizumab at 200 mg plus IV bevacizumab at 15 mg/kg every 3 weeks and oral cyclophosphamide at 50 mg every day. Patients were treated until disease progression or unacceptable toxicity.

Results

“The triple regimen was, overall, really well tolerated,” Dr. Zsiros said.

The most common grade 1/2 treatment-related adverse events (AEs) were fatigue (n = 14), diarrhea (n = 13), nausea (n = 9), hypertension (n =7), white blood cell decrease (n = 6), and arthralgia (n = 6).

Grade 3 related AEs included hypertension (n = 5), lymphocyte count decrease (n = 3), and white blood cell decrease (n = 1). There was one grade 4 drug-related AE of decreased lymphocyte count.

The overall response rate was 40%, with all 16 responders having a partial response. The rate of stable disease was 55% (n = 22).

“Only 2 patients out of the 40 progressed after initiation of the treatment, and I would like to point out that both of these patients had a very large disease burden,” Dr. Zsiros said.

She also noted that more than 77% of patients had a decrease in tumor size from baseline.

The disease control rate (partial response plus stable disease) was 95.0% (n = 38) initially and 62.5% (n = 25) at 6 months. However, three patients had not yet reached 6 months follow-up at the data cutoff.

“I would like to point out that 30% of the patients [n = 12] derived an especially long-term clinical benefit over 12 months and 12 cycles of treatment,” Dr. Zsiros said.

She added that quality of life assessment revealed “high physical, emotional, cognitive, and social functioning throughout the clinical trial.” The researchers also observed significantly improved body image from baseline (P less than .002).

Dr. Zsiros reported relationships with Iovance Biotherapeutics and AstraZeneca. The trial was sponsored by Roswell Park Cancer Institute in collaboration with the National Cancer Institute.

jensmith@mdedge.com

SOURCE: Zsiros E et al. SGO 2019, Abstract LBA4.

Metformin is especially effective in diabetes prevention among persons with higher baseline fasting glucose, higher hemoglobin A1c (HbA1c), or a history of gestational diabetes, based on 15-year follow-up results from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study.

Beyond those subgroups, metformin remained effective regardless of how diabetes was diagnosed, with a risk reduction of up to 36%, according to a report published in Diabetes Care.

“These results should help to prioritize those groups at high risk of developing diabetes who will benefit most from being treated with metformin,” said the report’s writing committee, chaired by David M. Nathan, MD, professor of medicine at Harvard Medical School, Boston.

However, the link between higher HbA1c and better efficacy of metformin should be “considered carefully,” according to Dr. Nathan and his cocommittee members, who noted that the original criteria for the Diabetes Prevention Program study were based on glucose level, rather than HbA1c level.

Initial results of the Diabetes Prevention Program study indicated a particular benefit of metformin after an average of 2.8 years of follow-up in individuals with higher baseline fasting glucose levels and in women with a self-reported history of gestational diabetes (N Engl J Med. 2002 Feb 7;346[6]:393-403).

Those results prompted the American Diabetes Association and others to recommend consideration of metformin for diabetes prevention in individuals considered to be at high risk, Dr. Nathan and his colleagues noted. “This recommendation is further supported by the demonstrated cost savings of metformin in diabetes prevention.”

The Diabetes Prevention Program study originally included 3,234 high-risk participants enrolled between 1996 and 1999 and randomized to masked metformin, placebo, or intensive lifestyle intervention. The 15-year follow-up analysis considered the 2,155 individuals randomized to the metformin or placebo groups, of whom 1,861 (86%) chose to continue in the Diabetes Prevention Program Outcomes Study, in which they continued to receive metformin unmasked.

Over the 15 years, the incidence of diabetes development based on fasting or 2-hour glucose results was 17% lower in the metformin group, compared with the placebo group (hazard ratio, 0.83; or –1.25 cases per 100 person-years), according to Dr. Nathan and his colleagues.

For diabetes development based on HbA1c level, metformin was linked to a 36% reduction in risk, compared with placebo, or –1.67 cases per 100 person-years.

Higher baseline fasting plasma glucose (110-125 mg/dL vs. 95-109 mg/dL) was associated with a greater effect of metformin in reducing diabetes development over 15 years (P = .0004).

Metformin’s effect in reducing diabetes development was “nearly identical” in participants with an HbA1c of 6.0%-6.4%, compared with less than 6.0%, with HRs of 0.63 and 0.61, respectively; however, looking at rate differences, there was “substantial heterogeneity” between the groups, at –3.88 and –1.03 cases per 100 person-years, respectively, the investigators wrote.

For women with a history of gestational diabetes, metformin was linked to a 41% reduction in diabetes development, compared with placebo (P = .03); in women without gestational diabetes, the difference was a nonsignificant 6% reduction, compared with placebo. In terms of risk differences, this translated into a reduction of 4.57 cases per 100 person-years in women with gestational diabetes, compared with a reduction of just 0.38 cases in women without such a history. The authors noted that it is “complicated” to determine whether greater credence be given to the results based on glucose or those based on HbA1c.

On the one hand, the generalizability of the HbA1c analyses is adversely affected because the analyses were performed post hoc on a set of participants who had initially been selected for the study based on prediabetes defined by glucose. On the other, the HbA1c results may be more clinically relevant because “in many countries, oral glucose tolerance tests are not used routinely for the identification of persons at high risk for diabetes or with diabetes,” the authors wrote.

Continued follow-up of these patients will provide additional data on the potential long-term benefits of metformin use, such as the incidence of cardiovascular disease, cancer, and microvascular disease, the investigators concluded.

The National Institute of Diabetes and Digestive and Kidney Diseases and Department of Veterans Affairs, among others, funded the Diabetes Prevention Program and subsequent outcomes study. Lipha provided medication and LifeScan donated materials during the studies. Additional funding to the Diabetes Prevention Program was provided by Bristol-Myers Squibb and Parke-Davis.

SOURCE: Nathan DM et al. Diabetes Care. 2019 Mar 15. doi: 10.2337/dc18-1970.

Metformin is especially effective in diabetes prevention among persons with higher baseline fasting glucose, higher hemoglobin A1c (HbA1c), or a history of gestational diabetes, based on 15-year follow-up results from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study.

Beyond those subgroups, metformin remained effective regardless of how diabetes was diagnosed, with a risk reduction of up to 36%, according to a report published in Diabetes Care.

“These results should help to prioritize those groups at high risk of developing diabetes who will benefit most from being treated with metformin,” said the report’s writing committee, chaired by David M. Nathan, MD, professor of medicine at Harvard Medical School, Boston.

However, the link between higher HbA1c and better efficacy of metformin should be “considered carefully,” according to Dr. Nathan and his cocommittee members, who noted that the original criteria for the Diabetes Prevention Program study were based on glucose level, rather than HbA1c level.

Initial results of the Diabetes Prevention Program study indicated a particular benefit of metformin after an average of 2.8 years of follow-up in individuals with higher baseline fasting glucose levels and in women with a self-reported history of gestational diabetes (N Engl J Med. 2002 Feb 7;346[6]:393-403).

Those results prompted the American Diabetes Association and others to recommend consideration of metformin for diabetes prevention in individuals considered to be at high risk, Dr. Nathan and his colleagues noted. “This recommendation is further supported by the demonstrated cost savings of metformin in diabetes prevention.”

The Diabetes Prevention Program study originally included 3,234 high-risk participants enrolled between 1996 and 1999 and randomized to masked metformin, placebo, or intensive lifestyle intervention. The 15-year follow-up analysis considered the 2,155 individuals randomized to the metformin or placebo groups, of whom 1,861 (86%) chose to continue in the Diabetes Prevention Program Outcomes Study, in which they continued to receive metformin unmasked.

Over the 15 years, the incidence of diabetes development based on fasting or 2-hour glucose results was 17% lower in the metformin group, compared with the placebo group (hazard ratio, 0.83; or –1.25 cases per 100 person-years), according to Dr. Nathan and his colleagues.

For diabetes development based on HbA1c level, metformin was linked to a 36% reduction in risk, compared with placebo, or –1.67 cases per 100 person-years.

Higher baseline fasting plasma glucose (110-125 mg/dL vs. 95-109 mg/dL) was associated with a greater effect of metformin in reducing diabetes development over 15 years (P = .0004).

Metformin’s effect in reducing diabetes development was “nearly identical” in participants with an HbA1c of 6.0%-6.4%, compared with less than 6.0%, with HRs of 0.63 and 0.61, respectively; however, looking at rate differences, there was “substantial heterogeneity” between the groups, at –3.88 and –1.03 cases per 100 person-years, respectively, the investigators wrote.

For women with a history of gestational diabetes, metformin was linked to a 41% reduction in diabetes development, compared with placebo (P = .03); in women without gestational diabetes, the difference was a nonsignificant 6% reduction, compared with placebo. In terms of risk differences, this translated into a reduction of 4.57 cases per 100 person-years in women with gestational diabetes, compared with a reduction of just 0.38 cases in women without such a history. The authors noted that it is “complicated” to determine whether greater credence be given to the results based on glucose or those based on HbA1c.

On the one hand, the generalizability of the HbA1c analyses is adversely affected because the analyses were performed post hoc on a set of participants who had initially been selected for the study based on prediabetes defined by glucose. On the other, the HbA1c results may be more clinically relevant because “in many countries, oral glucose tolerance tests are not used routinely for the identification of persons at high risk for diabetes or with diabetes,” the authors wrote.

Continued follow-up of these patients will provide additional data on the potential long-term benefits of metformin use, such as the incidence of cardiovascular disease, cancer, and microvascular disease, the investigators concluded.

The National Institute of Diabetes and Digestive and Kidney Diseases and Department of Veterans Affairs, among others, funded the Diabetes Prevention Program and subsequent outcomes study. Lipha provided medication and LifeScan donated materials during the studies. Additional funding to the Diabetes Prevention Program was provided by Bristol-Myers Squibb and Parke-Davis.

SOURCE: Nathan DM et al. Diabetes Care. 2019 Mar 15. doi: 10.2337/dc18-1970.

Metformin is especially effective in diabetes prevention among persons with higher baseline fasting glucose, higher hemoglobin A1c (HbA1c), or a history of gestational diabetes, based on 15-year follow-up results from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study.

Beyond those subgroups, metformin remained effective regardless of how diabetes was diagnosed, with a risk reduction of up to 36%, according to a report published in Diabetes Care.

“These results should help to prioritize those groups at high risk of developing diabetes who will benefit most from being treated with metformin,” said the report’s writing committee, chaired by David M. Nathan, MD, professor of medicine at Harvard Medical School, Boston.

However, the link between higher HbA1c and better efficacy of metformin should be “considered carefully,” according to Dr. Nathan and his cocommittee members, who noted that the original criteria for the Diabetes Prevention Program study were based on glucose level, rather than HbA1c level.

Initial results of the Diabetes Prevention Program study indicated a particular benefit of metformin after an average of 2.8 years of follow-up in individuals with higher baseline fasting glucose levels and in women with a self-reported history of gestational diabetes (N Engl J Med. 2002 Feb 7;346[6]:393-403).

Those results prompted the American Diabetes Association and others to recommend consideration of metformin for diabetes prevention in individuals considered to be at high risk, Dr. Nathan and his colleagues noted. “This recommendation is further supported by the demonstrated cost savings of metformin in diabetes prevention.”

The Diabetes Prevention Program study originally included 3,234 high-risk participants enrolled between 1996 and 1999 and randomized to masked metformin, placebo, or intensive lifestyle intervention. The 15-year follow-up analysis considered the 2,155 individuals randomized to the metformin or placebo groups, of whom 1,861 (86%) chose to continue in the Diabetes Prevention Program Outcomes Study, in which they continued to receive metformin unmasked.

Over the 15 years, the incidence of diabetes development based on fasting or 2-hour glucose results was 17% lower in the metformin group, compared with the placebo group (hazard ratio, 0.83; or –1.25 cases per 100 person-years), according to Dr. Nathan and his colleagues.

For diabetes development based on HbA1c level, metformin was linked to a 36% reduction in risk, compared with placebo, or –1.67 cases per 100 person-years.

Higher baseline fasting plasma glucose (110-125 mg/dL vs. 95-109 mg/dL) was associated with a greater effect of metformin in reducing diabetes development over 15 years (P = .0004).

Metformin’s effect in reducing diabetes development was “nearly identical” in participants with an HbA1c of 6.0%-6.4%, compared with less than 6.0%, with HRs of 0.63 and 0.61, respectively; however, looking at rate differences, there was “substantial heterogeneity” between the groups, at –3.88 and –1.03 cases per 100 person-years, respectively, the investigators wrote.

For women with a history of gestational diabetes, metformin was linked to a 41% reduction in diabetes development, compared with placebo (P = .03); in women without gestational diabetes, the difference was a nonsignificant 6% reduction, compared with placebo. In terms of risk differences, this translated into a reduction of 4.57 cases per 100 person-years in women with gestational diabetes, compared with a reduction of just 0.38 cases in women without such a history. The authors noted that it is “complicated” to determine whether greater credence be given to the results based on glucose or those based on HbA1c.

On the one hand, the generalizability of the HbA1c analyses is adversely affected because the analyses were performed post hoc on a set of participants who had initially been selected for the study based on prediabetes defined by glucose. On the other, the HbA1c results may be more clinically relevant because “in many countries, oral glucose tolerance tests are not used routinely for the identification of persons at high risk for diabetes or with diabetes,” the authors wrote.

Continued follow-up of these patients will provide additional data on the potential long-term benefits of metformin use, such as the incidence of cardiovascular disease, cancer, and microvascular disease, the investigators concluded.

The National Institute of Diabetes and Digestive and Kidney Diseases and Department of Veterans Affairs, among others, funded the Diabetes Prevention Program and subsequent outcomes study. Lipha provided medication and LifeScan donated materials during the studies. Additional funding to the Diabetes Prevention Program was provided by Bristol-Myers Squibb and Parke-Davis.

SOURCE: Nathan DM et al. Diabetes Care. 2019 Mar 15. doi: 10.2337/dc18-1970.

NEW ORLEANS – Patients with severely symptomatic aortic stenosis at low surgical risk had significantly better key outcomes with transcatheter aortic valve replacement than with surgical valve replacement through 1 year of follow-up in the landmark PARTNER 3 and Evolut Low Risk randomized trials presented at the annual meeting of the American College of Cardiology.

Bruce Jancin/MDedge News

As the two study presenters stepped down from the stage after sharing their results, the packed audience in the meeting’s main arena rose to shower them with a prolonged standing ovation.

“This is a historic moment, and all of us here should recognize it as such,” thundered discussant Eugene Braunwald, MD, professor of medicine at Harvard Medical School, Boston. “We’re going to remember it. We’re going to tell our grandchildren and great grandchildren that we were there at the time these incredible advances in the care of patients with aortic stenosis were presented.”

This was in fact the day that transcatheter aortic valve replacement (TAVR), a relatively young, rapidly evolving nonsurgical technique, finally overtook surgical aortic valve replacement (SAVR), a mature operation first successfully performed back in 1962. Previous large, randomized trials had established that TAVR was superior to SAVR in extreme-risk patients and noninferior to surgery in high- and intermediate-risk patients, yet with the advantage of much quicker recovery. The only remaining question was how TAVR would stack up in low-risk patients, who comprise 80% of those who currently undergo SAVR for aortic stenosis.

“Two separate groups using two separate valves have come to very similar conclusions. This doesn’t double the acceptability, it quadruples it,” Dr. Braunwald said.

PARTNER 3

Martin B. Leon, MD, presented the findings of the PARTNER 3 (Placement of Aortic Transcatheter Valves) trial, in which 1,000 low-risk patients at 71 centers were randomized to TAVR with transfemoral placement of the balloon-expandable Edwards Lifesciences Sapien 3 bioprosthetic valve or to SAVR. The mean age of the patients was 73 years, with a mean Society of Thoracic Surgeons risk score of 1.9%. Operators had to have more than 1 year of experience using the Sapien 3 valve in order to participate in the trial.

Bruce Jancin/MDedge News

At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with SAVR, for a highly significant 46% relative risk reduction. All three components of the primary endpoint occurred significantly less often in the TAVR group. And the rate of the key endpoint of death or disabling stroke was 1.0% with TAVR, compared with 2.9% with SAVR, reported Dr. Leon, coprincipal investigator in PARTNER 3 and professor of medicine at Columbia University, New York.

TAVR also outperformed SAVR on all six prespecified major secondary endpoints. These included new-onset atrial fibrillation within 30 days, at 5.0% with TAVR and 39.5% with SAVR; length of index hospitalization at 3 versus 7 days; all stroke at 30 days at 0.6% versus 2.4%; and death or a significant deterioration in quality of life at 30 days as measured by the Kansas City Cardiomyopathy Questionnaire at 3.9% versus 30.6%. There was significantly less life-threatening or major bleeding within 30 days in the TAVR group, by a margin of 3.6% versus 24.5%, and similarly low rates of new pacemaker implantation at 6.5% versus 4.0%. There was, however, a higher 30-day incidence of new left bundle branch block with TAVR, by a margin of 22% versus 8%, which may eventually translate into need for a pacemaker.

“Based upon these findings, TAVR, through 1 year, should be considered the preferred therapy in low-surgical-risk aortic stenosis patients. The PARTNER randomized trials over the past 12 years clearly indicate that the relative value of TAVR, compared with surgery, is independent of surgical risk profiles,” Dr. Leon declared.

Evolut Low Risk

Michael J. Reardon, MD, coprincipal investigator for the Evolut Low Risk study and professor of cardiovascular surgery at Houston Methodist Hospital, reported on 1,468 patients randomized to TAVR with a Medtronic self-expanding, supra-annular bioprosthetic valve or to SAVR. Of them, 22% of patients got the most recent version of the valve, known as the Evolut PRO, 74% got the Evolut R, and the remainder received the first-generation CoreValve.

Bruce Jancin/MDedge News

The primary endpoint – death or disabling stroke – was slightly different from that in PARTNER 3. At 1 year, the rate was 2.9% in the TAVR arm and 4.6% with SAVR, a statistically significant difference, while at 2 years the rate was 5.3% with TAVR and 6.7% with SAVR, a difference that was not significant. Impressively, the rate of the composite of death, disabling stroke, or heart failure hospitalizations through 1 year was 5.6% with TAVR versus 10.2% with SAVR.

“We’ve shown that, with TAVR, you’re more likely to be alive, without a stroke, and outside the hospital. This is exactly what my patients tell me they want when we sit down for shared decision-making and talk about their expectations,” Dr. Reardon said.

Noting the striking similarity of across-the-board outcomes in the two trials, Dr. Reardon concluded, “I think what we’re seeing here is a class effect of TAVR, and we have to recognize it as such.”

Dr. Leon agreed, with a caveat. “I think the class effect for these two versions of TAVR systems is very real. I wouldn’t presume to think that every TAVR device will perform the same way, so I think we need a lot more data on the newer devices that are being introduced.”

The reaction

During the question-and-answer session, the two investigators were asked about stroke rates, which were significantly lower in the TAVR patients even though in the early randomized trials in high-risk patients the stroke rates were twice as high with TAVR than SAVR. The explanation probably lies in a mix of device refinements over time, better techniques, standardized procedures, and careful patient selection, they said.

“If you look at stroke in the TAVR arm in both these trials, we’re almost approaching the background stroke rate in a group of 74-year-olds sitting around in a room,” Dr. Reardon observed.

Both trials will continue to assess participants both clinically and by echocardiography through 10 years, in part to assess TAVR valve durability, but also to evaluate the durability of surgical valves, which isn’t nearly as well established as most people think, according to the investigators.

“There is a myth of surgical bioprosthetic valve immortality. It’s based upon relatively few numbers of patients, largely sponsor-based studies, with numbers at risk at 15-20 years that are extremely low,” Dr. Leon asserted. “The majority of surgical valves being used today and touted as being durable are backed by only 2-4 years of data.”

In contrast, he added, “We have 5-year TAVR data which is absolutely definitive of no early structural valve deterioration.”

Discussant Mayra E. Guerrero, MD, of the Mayo Clinic in Rochester, Minn., expressed concern that “this paradigm shift to ‘TAVR for all’ ” could break the bank for many institutions because the cost of TAVR valves is far greater than for SAVR valves. But she was heartened by the fresh PARTNER 3 and Evolut Low Risk data showing TAVR patients had fewer ICU days, shorter hospital stays, fewer strokes, more frequent discharge home, and a lower rehospitalization rate.

Dr. Reardon was reassuring on this score.

“I am 100% convinced that when we do the financials for these two trials, TAVR is going to be a cost saver and a huge winner,” the surgeon said.

He reported serving as a consultant to Medtronic and receiving research grants from Medtronic and Boston Scientific. Dr. Leon reported receiving research grants from Edwards Lifesciences and St. Jude Medical and acting as a consultant to several medical device companies.

The two trials have been published online by the New England Journal of Medicine.

bjancin@mdedge.com

SOURCES: Leon MB et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052; Reardon MJ et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1816885.

NEW ORLEANS – Patients with severely symptomatic aortic stenosis at low surgical risk had significantly better key outcomes with transcatheter aortic valve replacement than with surgical valve replacement through 1 year of follow-up in the landmark PARTNER 3 and Evolut Low Risk randomized trials presented at the annual meeting of the American College of Cardiology.

Bruce Jancin/MDedge News

As the two study presenters stepped down from the stage after sharing their results, the packed audience in the meeting’s main arena rose to shower them with a prolonged standing ovation.

“This is a historic moment, and all of us here should recognize it as such,” thundered discussant Eugene Braunwald, MD, professor of medicine at Harvard Medical School, Boston. “We’re going to remember it. We’re going to tell our grandchildren and great grandchildren that we were there at the time these incredible advances in the care of patients with aortic stenosis were presented.”

This was in fact the day that transcatheter aortic valve replacement (TAVR), a relatively young, rapidly evolving nonsurgical technique, finally overtook surgical aortic valve replacement (SAVR), a mature operation first successfully performed back in 1962. Previous large, randomized trials had established that TAVR was superior to SAVR in extreme-risk patients and noninferior to surgery in high- and intermediate-risk patients, yet with the advantage of much quicker recovery. The only remaining question was how TAVR would stack up in low-risk patients, who comprise 80% of those who currently undergo SAVR for aortic stenosis.

“Two separate groups using two separate valves have come to very similar conclusions. This doesn’t double the acceptability, it quadruples it,” Dr. Braunwald said.

PARTNER 3

Martin B. Leon, MD, presented the findings of the PARTNER 3 (Placement of Aortic Transcatheter Valves) trial, in which 1,000 low-risk patients at 71 centers were randomized to TAVR with transfemoral placement of the balloon-expandable Edwards Lifesciences Sapien 3 bioprosthetic valve or to SAVR. The mean age of the patients was 73 years, with a mean Society of Thoracic Surgeons risk score of 1.9%. Operators had to have more than 1 year of experience using the Sapien 3 valve in order to participate in the trial.

Bruce Jancin/MDedge News

At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with SAVR, for a highly significant 46% relative risk reduction. All three components of the primary endpoint occurred significantly less often in the TAVR group. And the rate of the key endpoint of death or disabling stroke was 1.0% with TAVR, compared with 2.9% with SAVR, reported Dr. Leon, coprincipal investigator in PARTNER 3 and professor of medicine at Columbia University, New York.

TAVR also outperformed SAVR on all six prespecified major secondary endpoints. These included new-onset atrial fibrillation within 30 days, at 5.0% with TAVR and 39.5% with SAVR; length of index hospitalization at 3 versus 7 days; all stroke at 30 days at 0.6% versus 2.4%; and death or a significant deterioration in quality of life at 30 days as measured by the Kansas City Cardiomyopathy Questionnaire at 3.9% versus 30.6%. There was significantly less life-threatening or major bleeding within 30 days in the TAVR group, by a margin of 3.6% versus 24.5%, and similarly low rates of new pacemaker implantation at 6.5% versus 4.0%. There was, however, a higher 30-day incidence of new left bundle branch block with TAVR, by a margin of 22% versus 8%, which may eventually translate into need for a pacemaker.

“Based upon these findings, TAVR, through 1 year, should be considered the preferred therapy in low-surgical-risk aortic stenosis patients. The PARTNER randomized trials over the past 12 years clearly indicate that the relative value of TAVR, compared with surgery, is independent of surgical risk profiles,” Dr. Leon declared.

Evolut Low Risk

Michael J. Reardon, MD, coprincipal investigator for the Evolut Low Risk study and professor of cardiovascular surgery at Houston Methodist Hospital, reported on 1,468 patients randomized to TAVR with a Medtronic self-expanding, supra-annular bioprosthetic valve or to SAVR. Of them, 22% of patients got the most recent version of the valve, known as the Evolut PRO, 74% got the Evolut R, and the remainder received the first-generation CoreValve.

Bruce Jancin/MDedge News

The primary endpoint – death or disabling stroke – was slightly different from that in PARTNER 3. At 1 year, the rate was 2.9% in the TAVR arm and 4.6% with SAVR, a statistically significant difference, while at 2 years the rate was 5.3% with TAVR and 6.7% with SAVR, a difference that was not significant. Impressively, the rate of the composite of death, disabling stroke, or heart failure hospitalizations through 1 year was 5.6% with TAVR versus 10.2% with SAVR.

“We’ve shown that, with TAVR, you’re more likely to be alive, without a stroke, and outside the hospital. This is exactly what my patients tell me they want when we sit down for shared decision-making and talk about their expectations,” Dr. Reardon said.

Noting the striking similarity of across-the-board outcomes in the two trials, Dr. Reardon concluded, “I think what we’re seeing here is a class effect of TAVR, and we have to recognize it as such.”

Dr. Leon agreed, with a caveat. “I think the class effect for these two versions of TAVR systems is very real. I wouldn’t presume to think that every TAVR device will perform the same way, so I think we need a lot more data on the newer devices that are being introduced.”

The reaction

During the question-and-answer session, the two investigators were asked about stroke rates, which were significantly lower in the TAVR patients even though in the early randomized trials in high-risk patients the stroke rates were twice as high with TAVR than SAVR. The explanation probably lies in a mix of device refinements over time, better techniques, standardized procedures, and careful patient selection, they said.

“If you look at stroke in the TAVR arm in both these trials, we’re almost approaching the background stroke rate in a group of 74-year-olds sitting around in a room,” Dr. Reardon observed.

Both trials will continue to assess participants both clinically and by echocardiography through 10 years, in part to assess TAVR valve durability, but also to evaluate the durability of surgical valves, which isn’t nearly as well established as most people think, according to the investigators.

“There is a myth of surgical bioprosthetic valve immortality. It’s based upon relatively few numbers of patients, largely sponsor-based studies, with numbers at risk at 15-20 years that are extremely low,” Dr. Leon asserted. “The majority of surgical valves being used today and touted as being durable are backed by only 2-4 years of data.”

In contrast, he added, “We have 5-year TAVR data which is absolutely definitive of no early structural valve deterioration.”

Discussant Mayra E. Guerrero, MD, of the Mayo Clinic in Rochester, Minn., expressed concern that “this paradigm shift to ‘TAVR for all’ ” could break the bank for many institutions because the cost of TAVR valves is far greater than for SAVR valves. But she was heartened by the fresh PARTNER 3 and Evolut Low Risk data showing TAVR patients had fewer ICU days, shorter hospital stays, fewer strokes, more frequent discharge home, and a lower rehospitalization rate.

Dr. Reardon was reassuring on this score.

“I am 100% convinced that when we do the financials for these two trials, TAVR is going to be a cost saver and a huge winner,” the surgeon said.

He reported serving as a consultant to Medtronic and receiving research grants from Medtronic and Boston Scientific. Dr. Leon reported receiving research grants from Edwards Lifesciences and St. Jude Medical and acting as a consultant to several medical device companies.

The two trials have been published online by the New England Journal of Medicine.

bjancin@mdedge.com

SOURCES: Leon MB et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052; Reardon MJ et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1816885.

NEW ORLEANS – Patients with severely symptomatic aortic stenosis at low surgical risk had significantly better key outcomes with transcatheter aortic valve replacement than with surgical valve replacement through 1 year of follow-up in the landmark PARTNER 3 and Evolut Low Risk randomized trials presented at the annual meeting of the American College of Cardiology.

Bruce Jancin/MDedge News

As the two study presenters stepped down from the stage after sharing their results, the packed audience in the meeting’s main arena rose to shower them with a prolonged standing ovation.

“This is a historic moment, and all of us here should recognize it as such,” thundered discussant Eugene Braunwald, MD, professor of medicine at Harvard Medical School, Boston. “We’re going to remember it. We’re going to tell our grandchildren and great grandchildren that we were there at the time these incredible advances in the care of patients with aortic stenosis were presented.”

This was in fact the day that transcatheter aortic valve replacement (TAVR), a relatively young, rapidly evolving nonsurgical technique, finally overtook surgical aortic valve replacement (SAVR), a mature operation first successfully performed back in 1962. Previous large, randomized trials had established that TAVR was superior to SAVR in extreme-risk patients and noninferior to surgery in high- and intermediate-risk patients, yet with the advantage of much quicker recovery. The only remaining question was how TAVR would stack up in low-risk patients, who comprise 80% of those who currently undergo SAVR for aortic stenosis.

“Two separate groups using two separate valves have come to very similar conclusions. This doesn’t double the acceptability, it quadruples it,” Dr. Braunwald said.

PARTNER 3

Martin B. Leon, MD, presented the findings of the PARTNER 3 (Placement of Aortic Transcatheter Valves) trial, in which 1,000 low-risk patients at 71 centers were randomized to TAVR with transfemoral placement of the balloon-expandable Edwards Lifesciences Sapien 3 bioprosthetic valve or to SAVR. The mean age of the patients was 73 years, with a mean Society of Thoracic Surgeons risk score of 1.9%. Operators had to have more than 1 year of experience using the Sapien 3 valve in order to participate in the trial.

Bruce Jancin/MDedge News

At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with SAVR, for a highly significant 46% relative risk reduction. All three components of the primary endpoint occurred significantly less often in the TAVR group. And the rate of the key endpoint of death or disabling stroke was 1.0% with TAVR, compared with 2.9% with SAVR, reported Dr. Leon, coprincipal investigator in PARTNER 3 and professor of medicine at Columbia University, New York.

TAVR also outperformed SAVR on all six prespecified major secondary endpoints. These included new-onset atrial fibrillation within 30 days, at 5.0% with TAVR and 39.5% with SAVR; length of index hospitalization at 3 versus 7 days; all stroke at 30 days at 0.6% versus 2.4%; and death or a significant deterioration in quality of life at 30 days as measured by the Kansas City Cardiomyopathy Questionnaire at 3.9% versus 30.6%. There was significantly less life-threatening or major bleeding within 30 days in the TAVR group, by a margin of 3.6% versus 24.5%, and similarly low rates of new pacemaker implantation at 6.5% versus 4.0%. There was, however, a higher 30-day incidence of new left bundle branch block with TAVR, by a margin of 22% versus 8%, which may eventually translate into need for a pacemaker.

“Based upon these findings, TAVR, through 1 year, should be considered the preferred therapy in low-surgical-risk aortic stenosis patients. The PARTNER randomized trials over the past 12 years clearly indicate that the relative value of TAVR, compared with surgery, is independent of surgical risk profiles,” Dr. Leon declared.

Evolut Low Risk

Michael J. Reardon, MD, coprincipal investigator for the Evolut Low Risk study and professor of cardiovascular surgery at Houston Methodist Hospital, reported on 1,468 patients randomized to TAVR with a Medtronic self-expanding, supra-annular bioprosthetic valve or to SAVR. Of them, 22% of patients got the most recent version of the valve, known as the Evolut PRO, 74% got the Evolut R, and the remainder received the first-generation CoreValve.

Bruce Jancin/MDedge News

The primary endpoint – death or disabling stroke – was slightly different from that in PARTNER 3. At 1 year, the rate was 2.9% in the TAVR arm and 4.6% with SAVR, a statistically significant difference, while at 2 years the rate was 5.3% with TAVR and 6.7% with SAVR, a difference that was not significant. Impressively, the rate of the composite of death, disabling stroke, or heart failure hospitalizations through 1 year was 5.6% with TAVR versus 10.2% with SAVR.

“We’ve shown that, with TAVR, you’re more likely to be alive, without a stroke, and outside the hospital. This is exactly what my patients tell me they want when we sit down for shared decision-making and talk about their expectations,” Dr. Reardon said.

Noting the striking similarity of across-the-board outcomes in the two trials, Dr. Reardon concluded, “I think what we’re seeing here is a class effect of TAVR, and we have to recognize it as such.”

Dr. Leon agreed, with a caveat. “I think the class effect for these two versions of TAVR systems is very real. I wouldn’t presume to think that every TAVR device will perform the same way, so I think we need a lot more data on the newer devices that are being introduced.”

The reaction

During the question-and-answer session, the two investigators were asked about stroke rates, which were significantly lower in the TAVR patients even though in the early randomized trials in high-risk patients the stroke rates were twice as high with TAVR than SAVR. The explanation probably lies in a mix of device refinements over time, better techniques, standardized procedures, and careful patient selection, they said.

“If you look at stroke in the TAVR arm in both these trials, we’re almost approaching the background stroke rate in a group of 74-year-olds sitting around in a room,” Dr. Reardon observed.

Both trials will continue to assess participants both clinically and by echocardiography through 10 years, in part to assess TAVR valve durability, but also to evaluate the durability of surgical valves, which isn’t nearly as well established as most people think, according to the investigators.

“There is a myth of surgical bioprosthetic valve immortality. It’s based upon relatively few numbers of patients, largely sponsor-based studies, with numbers at risk at 15-20 years that are extremely low,” Dr. Leon asserted. “The majority of surgical valves being used today and touted as being durable are backed by only 2-4 years of data.”

In contrast, he added, “We have 5-year TAVR data which is absolutely definitive of no early structural valve deterioration.”

Discussant Mayra E. Guerrero, MD, of the Mayo Clinic in Rochester, Minn., expressed concern that “this paradigm shift to ‘TAVR for all’ ” could break the bank for many institutions because the cost of TAVR valves is far greater than for SAVR valves. But she was heartened by the fresh PARTNER 3 and Evolut Low Risk data showing TAVR patients had fewer ICU days, shorter hospital stays, fewer strokes, more frequent discharge home, and a lower rehospitalization rate.

Dr. Reardon was reassuring on this score.

“I am 100% convinced that when we do the financials for these two trials, TAVR is going to be a cost saver and a huge winner,” the surgeon said.

He reported serving as a consultant to Medtronic and receiving research grants from Medtronic and Boston Scientific. Dr. Leon reported receiving research grants from Edwards Lifesciences and St. Jude Medical and acting as a consultant to several medical device companies.

The two trials have been published online by the New England Journal of Medicine.

bjancin@mdedge.com

SOURCES: Leon MB et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052; Reardon MJ et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1816885.

ANSWER

The radiograph demonstrates a comminuted fracture of the superior end plate of L1. There is a loss of height of about 20% to 25%.

Of note, there is a lucency that appears to extend horizontally through the pedicles and into the spinous process. If this observation is accurate, then the patient would have a three-column injury. Such fractures are known as Chance fractures, and they are typically unstable and require operative intervention for stabilization.

Chance fractures are better visualized on CT. Subsequent testing confirmed a Chance fracture at the L1 level. The patient was admitted, and neurosurgical evaluation was requested.

ANSWER

The radiograph demonstrates a comminuted fracture of the superior end plate of L1. There is a loss of height of about 20% to 25%.

Of note, there is a lucency that appears to extend horizontally through the pedicles and into the spinous process. If this observation is accurate, then the patient would have a three-column injury. Such fractures are known as Chance fractures, and they are typically unstable and require operative intervention for stabilization.

Chance fractures are better visualized on CT. Subsequent testing confirmed a Chance fracture at the L1 level. The patient was admitted, and neurosurgical evaluation was requested.

ANSWER

The radiograph demonstrates a comminuted fracture of the superior end plate of L1. There is a loss of height of about 20% to 25%.

Of note, there is a lucency that appears to extend horizontally through the pedicles and into the spinous process. If this observation is accurate, then the patient would have a three-column injury. Such fractures are known as Chance fractures, and they are typically unstable and require operative intervention for stabilization.

Chance fractures are better visualized on CT. Subsequent testing confirmed a Chance fracture at the L1 level. The patient was admitted, and neurosurgical evaluation was requested.

The first medical society guideline to comprehensively address primary prevention of cardiovascular disease. Also today, a new coronary artery calcium score threshold may identify patients at particular risk, how to reduce the risk of drowning in pediatric patients, and an algorithm in smartwatches proves effective at detecting atrial fibrillation.
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The first medical society guideline to comprehensively address primary prevention of cardiovascular disease. Also today, a new coronary artery calcium score threshold may identify patients at particular risk, how to reduce the risk of drowning in pediatric patients, and an algorithm in smartwatches proves effective at detecting atrial fibrillation.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

The first medical society guideline to comprehensively address primary prevention of cardiovascular disease. Also today, a new coronary artery calcium score threshold may identify patients at particular risk, how to reduce the risk of drowning in pediatric patients, and an algorithm in smartwatches proves effective at detecting atrial fibrillation.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify