Gynecologic Cancer

The introduction of human papillomavirus vaccination in the United States in 2006 was associated with a significant decrease in the rates of cervical intraepithelial neoplasia grades 2 and above (CIN2+) in younger women.

The overall rate of CIN2+ declined from an estimated 216,000 cases in 2008 – 55% of which were in women aged 18-29 years – to 196,000 cases in 2016, of which 36% were in women aged 18-29 years, according to analysis of data from the Human Papillomavirus Vaccine Impact Monitoring Program (MMWR. 2019 Apr 19;68:337-43.

In 2008, the highest rates of CIN2+ were seen in women aged 20-24 years and decreased with age, but in 2016, the highest rates were in women aged 25-29 years. The rates of CIN2+ declined significantly in women aged 18-19 years from 2008-2016, but increased in women aged 40-64 years.

In 2008 and 2016, around three-quarters of all CIN2+ cases were attributable to HPV types that are targeted by the HPV vaccine. However the rates of vaccine-preventable CIN2+ declined among women aged 18-24 years, from 52% in 2008 to 30% in 2016.

“Both the estimated number and rates of U.S. CIN2+ cases in this report must be interpreted in the context of cervical cancer prevention strategies, including HPV vaccination and cervical cancer screening,” wrote Nancy M. McClung, PhD, of the Epidemic Intelligence Service at the Centers for Disease Control and Prevention and coauthors.

Notably, the screening interval for cervical cancer was increased from yearly in 2008 to once in 3 years with cytology alone or once in 5 years with cytology plus HPV testing for women aged 30 or above in 2016.

“Older age at screening initiation, longer screening intervals, and more conservative management in young women might be expected to reduce the number of CIN2+ cases detected in younger age groups in whom lesions are most likely to regress and shift detection of some CIN2+ to older age groups, resulting in a transient increase in rates,” Dr. McClung and colleagues wrote.

However they noted that the decrease in HPV 16/18–attributable CIN2+ rates among younger age groups was likely a reflection of the impact of the introduction of the quadrivalent vaccine immunization program.

One author declared personal fees from Merck during the course of the study. No other conflicts of interest were declared.

SOURCE: McClung N et al. MMWR. 2019 Apr 19;68:337-43.

The introduction of human papillomavirus vaccination in the United States in 2006 was associated with a significant decrease in the rates of cervical intraepithelial neoplasia grades 2 and above (CIN2+) in younger women.

The overall rate of CIN2+ declined from an estimated 216,000 cases in 2008 – 55% of which were in women aged 18-29 years – to 196,000 cases in 2016, of which 36% were in women aged 18-29 years, according to analysis of data from the Human Papillomavirus Vaccine Impact Monitoring Program (MMWR. 2019 Apr 19;68:337-43.

In 2008, the highest rates of CIN2+ were seen in women aged 20-24 years and decreased with age, but in 2016, the highest rates were in women aged 25-29 years. The rates of CIN2+ declined significantly in women aged 18-19 years from 2008-2016, but increased in women aged 40-64 years.

In 2008 and 2016, around three-quarters of all CIN2+ cases were attributable to HPV types that are targeted by the HPV vaccine. However the rates of vaccine-preventable CIN2+ declined among women aged 18-24 years, from 52% in 2008 to 30% in 2016.

“Both the estimated number and rates of U.S. CIN2+ cases in this report must be interpreted in the context of cervical cancer prevention strategies, including HPV vaccination and cervical cancer screening,” wrote Nancy M. McClung, PhD, of the Epidemic Intelligence Service at the Centers for Disease Control and Prevention and coauthors.

Notably, the screening interval for cervical cancer was increased from yearly in 2008 to once in 3 years with cytology alone or once in 5 years with cytology plus HPV testing for women aged 30 or above in 2016.

“Older age at screening initiation, longer screening intervals, and more conservative management in young women might be expected to reduce the number of CIN2+ cases detected in younger age groups in whom lesions are most likely to regress and shift detection of some CIN2+ to older age groups, resulting in a transient increase in rates,” Dr. McClung and colleagues wrote.

However they noted that the decrease in HPV 16/18–attributable CIN2+ rates among younger age groups was likely a reflection of the impact of the introduction of the quadrivalent vaccine immunization program.

One author declared personal fees from Merck during the course of the study. No other conflicts of interest were declared.

SOURCE: McClung N et al. MMWR. 2019 Apr 19;68:337-43.

The introduction of human papillomavirus vaccination in the United States in 2006 was associated with a significant decrease in the rates of cervical intraepithelial neoplasia grades 2 and above (CIN2+) in younger women.

The overall rate of CIN2+ declined from an estimated 216,000 cases in 2008 – 55% of which were in women aged 18-29 years – to 196,000 cases in 2016, of which 36% were in women aged 18-29 years, according to analysis of data from the Human Papillomavirus Vaccine Impact Monitoring Program (MMWR. 2019 Apr 19;68:337-43.

In 2008, the highest rates of CIN2+ were seen in women aged 20-24 years and decreased with age, but in 2016, the highest rates were in women aged 25-29 years. The rates of CIN2+ declined significantly in women aged 18-19 years from 2008-2016, but increased in women aged 40-64 years.

In 2008 and 2016, around three-quarters of all CIN2+ cases were attributable to HPV types that are targeted by the HPV vaccine. However the rates of vaccine-preventable CIN2+ declined among women aged 18-24 years, from 52% in 2008 to 30% in 2016.

“Both the estimated number and rates of U.S. CIN2+ cases in this report must be interpreted in the context of cervical cancer prevention strategies, including HPV vaccination and cervical cancer screening,” wrote Nancy M. McClung, PhD, of the Epidemic Intelligence Service at the Centers for Disease Control and Prevention and coauthors.

Notably, the screening interval for cervical cancer was increased from yearly in 2008 to once in 3 years with cytology alone or once in 5 years with cytology plus HPV testing for women aged 30 or above in 2016.

“Older age at screening initiation, longer screening intervals, and more conservative management in young women might be expected to reduce the number of CIN2+ cases detected in younger age groups in whom lesions are most likely to regress and shift detection of some CIN2+ to older age groups, resulting in a transient increase in rates,” Dr. McClung and colleagues wrote.

However they noted that the decrease in HPV 16/18–attributable CIN2+ rates among younger age groups was likely a reflection of the impact of the introduction of the quadrivalent vaccine immunization program.

One author declared personal fees from Merck during the course of the study. No other conflicts of interest were declared.

SOURCE: McClung N et al. MMWR. 2019 Apr 19;68:337-43.

TUCSON, ARIZ. – Use of the diuretic furosemide with cystoscopy for confirmation of ureteral patency results in a time savings of 78.5 seconds, according to results from a new randomized, controlled trial.

“It does make a difference, but is that really a [meaningful] difference? Every medication has adverse effects, so is it worth that extra time [savings] to take on that potential for side effects? It highlights the importance of statistical significance versus clinical significance, and I think [the clinical significance] can just be answered by each individual physician,” Simon Patton, MD, said in an interview.

Dr. Patton is a urogynecologist at Ascension Via Christi Medical Group in Wichita, Kan. He presented the study, which was conducted during his time as a fellow at the University of South Florida, Tampa, at the annual scientific meeting of the Society of Gynecologic Surgeons. Dr. Patton isn’t sure just how often physicians use furosemide during routine cystoscopy. “It would be great to do a survey to find out how many people use it in their practice,” he said.

Cystoscopy is used to during a surgery to ensure that no injury has been done to the bladder or the urethra, and the American Urogynecological Society recommends that it be performed during any pelvic reconstructive surgery. A key element of the test is confirming that the ureters are open. By increasing urine flow, furosemide can reduce the time to confirmation. But after conferring with a colleague who used the procedure, Dr. Patton looked for some data to support the practice and couldn’t find any.

Although the cystoscopy itself generally is safe, furosemide can cause hypotension, change in renal function, and even dehydration at higher doses. During the question-and-answer period, one attendee noted these issues and pointed out that furosemide can potentiate renal failure, especially among patients taking cephalosporins. “If you’re going to do this sort of trial, you have to consider potential adverse events. A single dose is probably not going to [cause an issue], but in the context of a study you want to monitor the adverse events that have been reported,” this attendee said.

The researchers did not observe any of these adverse events during the study, but Dr. Patton noted that the study was not powered to detect them. “We felt that with the low-dose, single-time [exposure], it was appropriate to not worry too much about those side effects,” he replied.

Another potential concern is that the increased urine flow could mask a kink in the ureter by forcing it open.

In the study, his team randomized 145 patients with a planned cystoscopy as part of a procedure to receive 10-mg furosemide (1 cc) or saline (1 cc) during a cystoscopy performed by an attending or a fellow. The median time to confirmation of ureteral patency was 86.5 seconds in the furosemide group, compared with 165.0 seconds in the saline group (difference, 78.5 seconds; P less than .001). The time to the first ureteral jet was 59 seconds versus 74 seconds, respectively (P less than .006). A Kaplan-Meier survival curve analysis also showed a significant improvement in time to ureteral patency confirmation (log-rank P less than .001).

The study was not funded. Dr. Patton has no relevant financial disclosures.

SOURCE: Patton S et al. SGS 2019, Abstract 10.

TUCSON, ARIZ. – Use of the diuretic furosemide with cystoscopy for confirmation of ureteral patency results in a time savings of 78.5 seconds, according to results from a new randomized, controlled trial.

“It does make a difference, but is that really a [meaningful] difference? Every medication has adverse effects, so is it worth that extra time [savings] to take on that potential for side effects? It highlights the importance of statistical significance versus clinical significance, and I think [the clinical significance] can just be answered by each individual physician,” Simon Patton, MD, said in an interview.

Dr. Patton is a urogynecologist at Ascension Via Christi Medical Group in Wichita, Kan. He presented the study, which was conducted during his time as a fellow at the University of South Florida, Tampa, at the annual scientific meeting of the Society of Gynecologic Surgeons. Dr. Patton isn’t sure just how often physicians use furosemide during routine cystoscopy. “It would be great to do a survey to find out how many people use it in their practice,” he said.

Cystoscopy is used to during a surgery to ensure that no injury has been done to the bladder or the urethra, and the American Urogynecological Society recommends that it be performed during any pelvic reconstructive surgery. A key element of the test is confirming that the ureters are open. By increasing urine flow, furosemide can reduce the time to confirmation. But after conferring with a colleague who used the procedure, Dr. Patton looked for some data to support the practice and couldn’t find any.

Although the cystoscopy itself generally is safe, furosemide can cause hypotension, change in renal function, and even dehydration at higher doses. During the question-and-answer period, one attendee noted these issues and pointed out that furosemide can potentiate renal failure, especially among patients taking cephalosporins. “If you’re going to do this sort of trial, you have to consider potential adverse events. A single dose is probably not going to [cause an issue], but in the context of a study you want to monitor the adverse events that have been reported,” this attendee said.

The researchers did not observe any of these adverse events during the study, but Dr. Patton noted that the study was not powered to detect them. “We felt that with the low-dose, single-time [exposure], it was appropriate to not worry too much about those side effects,” he replied.

Another potential concern is that the increased urine flow could mask a kink in the ureter by forcing it open.

In the study, his team randomized 145 patients with a planned cystoscopy as part of a procedure to receive 10-mg furosemide (1 cc) or saline (1 cc) during a cystoscopy performed by an attending or a fellow. The median time to confirmation of ureteral patency was 86.5 seconds in the furosemide group, compared with 165.0 seconds in the saline group (difference, 78.5 seconds; P less than .001). The time to the first ureteral jet was 59 seconds versus 74 seconds, respectively (P less than .006). A Kaplan-Meier survival curve analysis also showed a significant improvement in time to ureteral patency confirmation (log-rank P less than .001).

The study was not funded. Dr. Patton has no relevant financial disclosures.

SOURCE: Patton S et al. SGS 2019, Abstract 10.

TUCSON, ARIZ. – Use of the diuretic furosemide with cystoscopy for confirmation of ureteral patency results in a time savings of 78.5 seconds, according to results from a new randomized, controlled trial.

“It does make a difference, but is that really a [meaningful] difference? Every medication has adverse effects, so is it worth that extra time [savings] to take on that potential for side effects? It highlights the importance of statistical significance versus clinical significance, and I think [the clinical significance] can just be answered by each individual physician,” Simon Patton, MD, said in an interview.

Dr. Patton is a urogynecologist at Ascension Via Christi Medical Group in Wichita, Kan. He presented the study, which was conducted during his time as a fellow at the University of South Florida, Tampa, at the annual scientific meeting of the Society of Gynecologic Surgeons. Dr. Patton isn’t sure just how often physicians use furosemide during routine cystoscopy. “It would be great to do a survey to find out how many people use it in their practice,” he said.

Cystoscopy is used to during a surgery to ensure that no injury has been done to the bladder or the urethra, and the American Urogynecological Society recommends that it be performed during any pelvic reconstructive surgery. A key element of the test is confirming that the ureters are open. By increasing urine flow, furosemide can reduce the time to confirmation. But after conferring with a colleague who used the procedure, Dr. Patton looked for some data to support the practice and couldn’t find any.

Although the cystoscopy itself generally is safe, furosemide can cause hypotension, change in renal function, and even dehydration at higher doses. During the question-and-answer period, one attendee noted these issues and pointed out that furosemide can potentiate renal failure, especially among patients taking cephalosporins. “If you’re going to do this sort of trial, you have to consider potential adverse events. A single dose is probably not going to [cause an issue], but in the context of a study you want to monitor the adverse events that have been reported,” this attendee said.

The researchers did not observe any of these adverse events during the study, but Dr. Patton noted that the study was not powered to detect them. “We felt that with the low-dose, single-time [exposure], it was appropriate to not worry too much about those side effects,” he replied.

Another potential concern is that the increased urine flow could mask a kink in the ureter by forcing it open.

In the study, his team randomized 145 patients with a planned cystoscopy as part of a procedure to receive 10-mg furosemide (1 cc) or saline (1 cc) during a cystoscopy performed by an attending or a fellow. The median time to confirmation of ureteral patency was 86.5 seconds in the furosemide group, compared with 165.0 seconds in the saline group (difference, 78.5 seconds; P less than .001). The time to the first ureteral jet was 59 seconds versus 74 seconds, respectively (P less than .006). A Kaplan-Meier survival curve analysis also showed a significant improvement in time to ureteral patency confirmation (log-rank P less than .001).

The study was not funded. Dr. Patton has no relevant financial disclosures.

SOURCE: Patton S et al. SGS 2019, Abstract 10.

TUCSON, ARIZ. – Concomitant surgeries for endometrial cancer and stress urinary incontinence (SUI) led to better SUI outcomes than did cancer surgery with nonsurgical SUI therapy, according to a study examining the effects of an SUI screen among endometrial cancer patients.

Jim Kling/MDedge News

An estimated 40%-80% of women with endometrial cancer experience SUI. The malignancy often is caught early enough to be treated with curative intent, and that is leading physicians and patients to think more about quality of life outcomes.

And yet, few patients receive concomitant surgery. Twenty percent of the women in the current study opted for concomitant surgeries, yet large database studies show the frequency of concomitant surgeries is about 2.5%. “There’s huge room for improvement in this area. The take-home message is that this is prevalent, this is doable, and this is something that could truly benefit this population,” Evelyn Hall, MD, said in an interview. Dr. Hall is a fellow in female pelvic medicine and reconstructive medicine at Brown University, Providence, R.I. She presented the study at the annual scientific meeting of the Society of Gynecologic Surgeons.

It’s not entirely surprising that SUI tends to be overlooked in patients with endometrial cancer. After all, they are going through a life-changing medical diagnosis, and oncologists are laser focused on achieving a cure when possible. But a bigger picture view, especially in light of the high cure rate for endometrial cancer when detected early, should encourage physicians to think differently about patient management.

The biggest trick may be incorporating concomitant surgeries into the surgical work flow. “It can be challenging logistically. It requires surgical planning and coordination between the two surgeons,” said Dr. Hall. But she said the experience at Brown University showed that it was possible with some patience. “It took a while to get the balls rolling, but once we figured out [it] worked for our institution, we’ve seen a continued uptake,” she said.

An important remaining question is the safety of the concomitant surgeries. Dr. Hall did not report any between-group differences in her presentation, but analysis is ongoing. They found a statistically significant increase in the number of readmissions among the concomitant surgery group, but most were deemed unlikely to be related to concomitant surgery.

In the study, 1,322 endometrial surgical candidates were screened for SUI, and 53% tested positive. Of these, 556 patients were offered concomitant surgical or nonsurgical SUI treatment: 21% chose concomitant surgery, 19% chose nonsurgical SUI treatment, and 60% of patients opted for no SUI treatment.

At 6 months after surgery, the concomitant surgery group was more likely to have a Urinary Distress Inventory (UDI)–Stress score of 0 than were those who were treated nonsurgically (odds ratio, 2.8; P = .0001) and those in the no-treatment group (OR, 3.7; P less than .0001). The concomitant group also was more likely to have a surgical site infection (SSI) score of 0 than was the nonsurgical group (OR, 2.9; P = .0008) and the no-treatment group (OR, 2.7; P less than .0001). Severe/very severe SSI scores occurred in 57% of the concomitant group at baseline, and this frequency dropped to 14% at 6 weeks (P less than .0001).

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Hall has no relevant financial disclosures.

SOURCE: Hall E et al. SGS 2019, oral presentation 12.

TUCSON, ARIZ. – Concomitant surgeries for endometrial cancer and stress urinary incontinence (SUI) led to better SUI outcomes than did cancer surgery with nonsurgical SUI therapy, according to a study examining the effects of an SUI screen among endometrial cancer patients.

Jim Kling/MDedge News

An estimated 40%-80% of women with endometrial cancer experience SUI. The malignancy often is caught early enough to be treated with curative intent, and that is leading physicians and patients to think more about quality of life outcomes.

And yet, few patients receive concomitant surgery. Twenty percent of the women in the current study opted for concomitant surgeries, yet large database studies show the frequency of concomitant surgeries is about 2.5%. “There’s huge room for improvement in this area. The take-home message is that this is prevalent, this is doable, and this is something that could truly benefit this population,” Evelyn Hall, MD, said in an interview. Dr. Hall is a fellow in female pelvic medicine and reconstructive medicine at Brown University, Providence, R.I. She presented the study at the annual scientific meeting of the Society of Gynecologic Surgeons.

It’s not entirely surprising that SUI tends to be overlooked in patients with endometrial cancer. After all, they are going through a life-changing medical diagnosis, and oncologists are laser focused on achieving a cure when possible. But a bigger picture view, especially in light of the high cure rate for endometrial cancer when detected early, should encourage physicians to think differently about patient management.

The biggest trick may be incorporating concomitant surgeries into the surgical work flow. “It can be challenging logistically. It requires surgical planning and coordination between the two surgeons,” said Dr. Hall. But she said the experience at Brown University showed that it was possible with some patience. “It took a while to get the balls rolling, but once we figured out [it] worked for our institution, we’ve seen a continued uptake,” she said.

An important remaining question is the safety of the concomitant surgeries. Dr. Hall did not report any between-group differences in her presentation, but analysis is ongoing. They found a statistically significant increase in the number of readmissions among the concomitant surgery group, but most were deemed unlikely to be related to concomitant surgery.

In the study, 1,322 endometrial surgical candidates were screened for SUI, and 53% tested positive. Of these, 556 patients were offered concomitant surgical or nonsurgical SUI treatment: 21% chose concomitant surgery, 19% chose nonsurgical SUI treatment, and 60% of patients opted for no SUI treatment.

At 6 months after surgery, the concomitant surgery group was more likely to have a Urinary Distress Inventory (UDI)–Stress score of 0 than were those who were treated nonsurgically (odds ratio, 2.8; P = .0001) and those in the no-treatment group (OR, 3.7; P less than .0001). The concomitant group also was more likely to have a surgical site infection (SSI) score of 0 than was the nonsurgical group (OR, 2.9; P = .0008) and the no-treatment group (OR, 2.7; P less than .0001). Severe/very severe SSI scores occurred in 57% of the concomitant group at baseline, and this frequency dropped to 14% at 6 weeks (P less than .0001).

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Hall has no relevant financial disclosures.

SOURCE: Hall E et al. SGS 2019, oral presentation 12.

TUCSON, ARIZ. – Concomitant surgeries for endometrial cancer and stress urinary incontinence (SUI) led to better SUI outcomes than did cancer surgery with nonsurgical SUI therapy, according to a study examining the effects of an SUI screen among endometrial cancer patients.

Jim Kling/MDedge News

An estimated 40%-80% of women with endometrial cancer experience SUI. The malignancy often is caught early enough to be treated with curative intent, and that is leading physicians and patients to think more about quality of life outcomes.

And yet, few patients receive concomitant surgery. Twenty percent of the women in the current study opted for concomitant surgeries, yet large database studies show the frequency of concomitant surgeries is about 2.5%. “There’s huge room for improvement in this area. The take-home message is that this is prevalent, this is doable, and this is something that could truly benefit this population,” Evelyn Hall, MD, said in an interview. Dr. Hall is a fellow in female pelvic medicine and reconstructive medicine at Brown University, Providence, R.I. She presented the study at the annual scientific meeting of the Society of Gynecologic Surgeons.

It’s not entirely surprising that SUI tends to be overlooked in patients with endometrial cancer. After all, they are going through a life-changing medical diagnosis, and oncologists are laser focused on achieving a cure when possible. But a bigger picture view, especially in light of the high cure rate for endometrial cancer when detected early, should encourage physicians to think differently about patient management.

The biggest trick may be incorporating concomitant surgeries into the surgical work flow. “It can be challenging logistically. It requires surgical planning and coordination between the two surgeons,” said Dr. Hall. But she said the experience at Brown University showed that it was possible with some patience. “It took a while to get the balls rolling, but once we figured out [it] worked for our institution, we’ve seen a continued uptake,” she said.

An important remaining question is the safety of the concomitant surgeries. Dr. Hall did not report any between-group differences in her presentation, but analysis is ongoing. They found a statistically significant increase in the number of readmissions among the concomitant surgery group, but most were deemed unlikely to be related to concomitant surgery.

In the study, 1,322 endometrial surgical candidates were screened for SUI, and 53% tested positive. Of these, 556 patients were offered concomitant surgical or nonsurgical SUI treatment: 21% chose concomitant surgery, 19% chose nonsurgical SUI treatment, and 60% of patients opted for no SUI treatment.

At 6 months after surgery, the concomitant surgery group was more likely to have a Urinary Distress Inventory (UDI)–Stress score of 0 than were those who were treated nonsurgically (odds ratio, 2.8; P = .0001) and those in the no-treatment group (OR, 3.7; P less than .0001). The concomitant group also was more likely to have a surgical site infection (SSI) score of 0 than was the nonsurgical group (OR, 2.9; P = .0008) and the no-treatment group (OR, 2.7; P less than .0001). Severe/very severe SSI scores occurred in 57% of the concomitant group at baseline, and this frequency dropped to 14% at 6 weeks (P less than .0001).

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Hall has no relevant financial disclosures.

SOURCE: Hall E et al. SGS 2019, oral presentation 12.

The checkpoint inhibitor pembrolizumab conferred a durable tumor response in patients with advanced cervical cancer, who were positive for programmed death ligand 1 (PD-L1).

Among 98 patients, all of whom had progressed despite prior treatment, overall response rate was 12.2% (95% confidence interval, 6.5%-20.4%), with three complete and nine partial responses. All 12 responses were in patients with PD-L1-positive tumors, wrote Hyun Cheol Chung, MD, and his colleagues. The report is in the Journal of Clinical Oncology.

The response curve had not peaked by the end of follow-up, suggesting further benefit of the antibody, said Dr. Chung of Yonsei Cancer Center, Seoul, South Korea. On the basis of these data, first reported at the 2018 meeting of the American Society of Clinical Oncology, the Food and Drug Administration approved the antibody for advanced cervical cancer last year.

“These results show that treatment with pembrolizumab offers a clinically meaningful therapeutic option for a subset of patients with previously treated advanced cervical cancer,” the researchers said. The approval makes pembrolizumab the first immunotherapy approved for the treatment of an advanced gynecologic malignancy.

The phase 2 KEYNOTE-158 study comprised 98 women (median age 46 years) with advanced cervical cancer with progression after chemotherapy. All received pembrolizumab 200 mg every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision.

Most of the patients (83.7%) were positive for PD-L1. All had received at least one or more lines of chemotherapy before entering the study. The median follow-up was 10 months and the median treatment duration 2.9 months, with a range of 1 day-22 months.

By the study’s end, most patients (85.7%) had experienced disease progression or had died. Overall survival was poor even in the PD-L1-positive patients, with 82.9% experiencing progression or death. Overall mortality was 69.4% and 64.6%, respectively. However, PD-L1 patients did live longer, a median of 11 months, compared with 9.4 months in the entire cohort.

At 6 months, overall survival estimates were 75.2% in the total cohort and 80.2% in the PD-L1 patients; 12-month overall survival estimates were 41.4% and 47.3%, respectively.

However, among the 12 responders with PD-L1-postitive tumors, just one had died by the data cutoff, suggesting that longer treatment with pembrolizumab could be beneficial in this group.

“Responses typically occurred within 2.1 months and were durable, with a median duration of response that had not been reached after a median follow-up of 10.2 months and an estimated 90.9% of responses ongoing at 6 months” Dr. Chung and his colleagues wrote.

Adverse events were common (65.3%) with 12.2% graded as serious. But none were lethal, and only four patients discontinued pembrolizumab because of a treatment-related adverse event.

“Our results from an interim analysis of data from the phase II KEYNOTE-158 clinical trial show that pembrolizumab has promising antitumor activity in patients with previously treated advanced cervical cancer,” the researchers said. “These response rates are similar or superior to those observed with other treatment options in this setting.”

Pembrolizumab is now being evaluated in combination with concurrent chemoradiotherapy and with concurrent versus sequential chemoradiotherapy.

Merck & Co. sponsored the study.

[email protected]

SOURCE: Chung HC et al. J Clin Oncol. 2019 April 3. doi: 10.1200/JCO.18.01265.


 

The checkpoint inhibitor pembrolizumab conferred a durable tumor response in patients with advanced cervical cancer, who were positive for programmed death ligand 1 (PD-L1).

Among 98 patients, all of whom had progressed despite prior treatment, overall response rate was 12.2% (95% confidence interval, 6.5%-20.4%), with three complete and nine partial responses. All 12 responses were in patients with PD-L1-positive tumors, wrote Hyun Cheol Chung, MD, and his colleagues. The report is in the Journal of Clinical Oncology.

The response curve had not peaked by the end of follow-up, suggesting further benefit of the antibody, said Dr. Chung of Yonsei Cancer Center, Seoul, South Korea. On the basis of these data, first reported at the 2018 meeting of the American Society of Clinical Oncology, the Food and Drug Administration approved the antibody for advanced cervical cancer last year.

“These results show that treatment with pembrolizumab offers a clinically meaningful therapeutic option for a subset of patients with previously treated advanced cervical cancer,” the researchers said. The approval makes pembrolizumab the first immunotherapy approved for the treatment of an advanced gynecologic malignancy.

The phase 2 KEYNOTE-158 study comprised 98 women (median age 46 years) with advanced cervical cancer with progression after chemotherapy. All received pembrolizumab 200 mg every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision.

Most of the patients (83.7%) were positive for PD-L1. All had received at least one or more lines of chemotherapy before entering the study. The median follow-up was 10 months and the median treatment duration 2.9 months, with a range of 1 day-22 months.

By the study’s end, most patients (85.7%) had experienced disease progression or had died. Overall survival was poor even in the PD-L1-positive patients, with 82.9% experiencing progression or death. Overall mortality was 69.4% and 64.6%, respectively. However, PD-L1 patients did live longer, a median of 11 months, compared with 9.4 months in the entire cohort.

At 6 months, overall survival estimates were 75.2% in the total cohort and 80.2% in the PD-L1 patients; 12-month overall survival estimates were 41.4% and 47.3%, respectively.

However, among the 12 responders with PD-L1-postitive tumors, just one had died by the data cutoff, suggesting that longer treatment with pembrolizumab could be beneficial in this group.

“Responses typically occurred within 2.1 months and were durable, with a median duration of response that had not been reached after a median follow-up of 10.2 months and an estimated 90.9% of responses ongoing at 6 months” Dr. Chung and his colleagues wrote.

Adverse events were common (65.3%) with 12.2% graded as serious. But none were lethal, and only four patients discontinued pembrolizumab because of a treatment-related adverse event.

“Our results from an interim analysis of data from the phase II KEYNOTE-158 clinical trial show that pembrolizumab has promising antitumor activity in patients with previously treated advanced cervical cancer,” the researchers said. “These response rates are similar or superior to those observed with other treatment options in this setting.”

Pembrolizumab is now being evaluated in combination with concurrent chemoradiotherapy and with concurrent versus sequential chemoradiotherapy.

Merck & Co. sponsored the study.

[email protected]

SOURCE: Chung HC et al. J Clin Oncol. 2019 April 3. doi: 10.1200/JCO.18.01265.


 

The checkpoint inhibitor pembrolizumab conferred a durable tumor response in patients with advanced cervical cancer, who were positive for programmed death ligand 1 (PD-L1).

Among 98 patients, all of whom had progressed despite prior treatment, overall response rate was 12.2% (95% confidence interval, 6.5%-20.4%), with three complete and nine partial responses. All 12 responses were in patients with PD-L1-positive tumors, wrote Hyun Cheol Chung, MD, and his colleagues. The report is in the Journal of Clinical Oncology.

The response curve had not peaked by the end of follow-up, suggesting further benefit of the antibody, said Dr. Chung of Yonsei Cancer Center, Seoul, South Korea. On the basis of these data, first reported at the 2018 meeting of the American Society of Clinical Oncology, the Food and Drug Administration approved the antibody for advanced cervical cancer last year.

“These results show that treatment with pembrolizumab offers a clinically meaningful therapeutic option for a subset of patients with previously treated advanced cervical cancer,” the researchers said. The approval makes pembrolizumab the first immunotherapy approved for the treatment of an advanced gynecologic malignancy.

The phase 2 KEYNOTE-158 study comprised 98 women (median age 46 years) with advanced cervical cancer with progression after chemotherapy. All received pembrolizumab 200 mg every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision.

Most of the patients (83.7%) were positive for PD-L1. All had received at least one or more lines of chemotherapy before entering the study. The median follow-up was 10 months and the median treatment duration 2.9 months, with a range of 1 day-22 months.

By the study’s end, most patients (85.7%) had experienced disease progression or had died. Overall survival was poor even in the PD-L1-positive patients, with 82.9% experiencing progression or death. Overall mortality was 69.4% and 64.6%, respectively. However, PD-L1 patients did live longer, a median of 11 months, compared with 9.4 months in the entire cohort.

At 6 months, overall survival estimates were 75.2% in the total cohort and 80.2% in the PD-L1 patients; 12-month overall survival estimates were 41.4% and 47.3%, respectively.

However, among the 12 responders with PD-L1-postitive tumors, just one had died by the data cutoff, suggesting that longer treatment with pembrolizumab could be beneficial in this group.

“Responses typically occurred within 2.1 months and were durable, with a median duration of response that had not been reached after a median follow-up of 10.2 months and an estimated 90.9% of responses ongoing at 6 months” Dr. Chung and his colleagues wrote.

Adverse events were common (65.3%) with 12.2% graded as serious. But none were lethal, and only four patients discontinued pembrolizumab because of a treatment-related adverse event.

“Our results from an interim analysis of data from the phase II KEYNOTE-158 clinical trial show that pembrolizumab has promising antitumor activity in patients with previously treated advanced cervical cancer,” the researchers said. “These response rates are similar or superior to those observed with other treatment options in this setting.”

Pembrolizumab is now being evaluated in combination with concurrent chemoradiotherapy and with concurrent versus sequential chemoradiotherapy.

Merck & Co. sponsored the study.

[email protected]

SOURCE: Chung HC et al. J Clin Oncol. 2019 April 3. doi: 10.1200/JCO.18.01265.


 

For patients with endometrial cancer at high risk of progression, receiving a combination of taxane and platinum chemotherapy after surgery offers similar efficacy and tolerability as doxorubicin and cisplatin, the standard therapy, according to a recent phase 3 trial.

Progression-free and overall survival rates were similar across treatment types, reported lead author Hiroyuki Nomura, MD, of Keio University, Tokyo, and his colleagues. The findings maintain doxorubicin/cisplatin as standard therapy; however, taxane/platinum chemotherapy could be a possible alternative for some patients because of similar efficacy and tolerability with a distinct toxicity profile.

“Establishment of evidence and validation of the optimal postoperative adjuvant chemotherapy regimen for endometrial cancer are important issues,” the investigators wrote in JAMA Oncology.

The multicenter, open-label study involved 788 patients with endometrial cancer at risk of progression, based on histologic findings. Eligibility required that patients have a residual tumor of at least 2 cm without extension beyond the abdominal cavity. Patients were randomly grouped into one of three treatment groups: doxorubicin/cisplatin, paclitaxel/carboplatin, or docetaxel/cisplatin. If tolerated, six 3-week cycles were given. The median follow-up period was 7 years. The primary and secondary endpoints were 5-year progression free survival and overall survival, respectively.

Survival rates were statistically similar between groups. The 5-year progression-free survival rate was 73.3% for doxorubicin/cisplatin, 73.9% for paclitaxel/carboplatin, and 79.0% for docetaxel/cisplatin (P = .12); the 5-year overall survival rate was 82.7% for doxorubicin/cisplatin, 86.1% for paclitaxel/carboplatin, and 88.1% for docetaxel/cisplatin (P = .67). Tolerability was also comparable, with a small range of discontinuation rates across treatment types, from 20.2% to 25.5% (P = .14).

“Although the superiority of docetaxel plus cisplatin and paclitaxel plus carboplatin over doxorubicin plus cisplatin was not demonstrated, we found that the three regimens were comparable in therapeutic effect,” the investigators concluded. “[C]onsidering efficacy and tolerability, taxane plus platinum regimens may be an alternative to treatment with doxorubicin plus cisplatin.”

The study was funded by a Health Labour Sciences Research Grant with nonspecific funding from AstraZeneca, Eisai, Bristol-Myers Squibb, and others. The investigators reported financial relationships with Chugai, Sanofi, Takeda, AbbVie, and others.

SOURCE: Nomura H et al. JAMA Oncol. 2019 Mar 21. doi: 10.1001/jamaoncol.2019.0001.

For patients with endometrial cancer at high risk of progression, receiving a combination of taxane and platinum chemotherapy after surgery offers similar efficacy and tolerability as doxorubicin and cisplatin, the standard therapy, according to a recent phase 3 trial.

Progression-free and overall survival rates were similar across treatment types, reported lead author Hiroyuki Nomura, MD, of Keio University, Tokyo, and his colleagues. The findings maintain doxorubicin/cisplatin as standard therapy; however, taxane/platinum chemotherapy could be a possible alternative for some patients because of similar efficacy and tolerability with a distinct toxicity profile.

“Establishment of evidence and validation of the optimal postoperative adjuvant chemotherapy regimen for endometrial cancer are important issues,” the investigators wrote in JAMA Oncology.

The multicenter, open-label study involved 788 patients with endometrial cancer at risk of progression, based on histologic findings. Eligibility required that patients have a residual tumor of at least 2 cm without extension beyond the abdominal cavity. Patients were randomly grouped into one of three treatment groups: doxorubicin/cisplatin, paclitaxel/carboplatin, or docetaxel/cisplatin. If tolerated, six 3-week cycles were given. The median follow-up period was 7 years. The primary and secondary endpoints were 5-year progression free survival and overall survival, respectively.

Survival rates were statistically similar between groups. The 5-year progression-free survival rate was 73.3% for doxorubicin/cisplatin, 73.9% for paclitaxel/carboplatin, and 79.0% for docetaxel/cisplatin (P = .12); the 5-year overall survival rate was 82.7% for doxorubicin/cisplatin, 86.1% for paclitaxel/carboplatin, and 88.1% for docetaxel/cisplatin (P = .67). Tolerability was also comparable, with a small range of discontinuation rates across treatment types, from 20.2% to 25.5% (P = .14).

“Although the superiority of docetaxel plus cisplatin and paclitaxel plus carboplatin over doxorubicin plus cisplatin was not demonstrated, we found that the three regimens were comparable in therapeutic effect,” the investigators concluded. “[C]onsidering efficacy and tolerability, taxane plus platinum regimens may be an alternative to treatment with doxorubicin plus cisplatin.”

The study was funded by a Health Labour Sciences Research Grant with nonspecific funding from AstraZeneca, Eisai, Bristol-Myers Squibb, and others. The investigators reported financial relationships with Chugai, Sanofi, Takeda, AbbVie, and others.

SOURCE: Nomura H et al. JAMA Oncol. 2019 Mar 21. doi: 10.1001/jamaoncol.2019.0001.

For patients with endometrial cancer at high risk of progression, receiving a combination of taxane and platinum chemotherapy after surgery offers similar efficacy and tolerability as doxorubicin and cisplatin, the standard therapy, according to a recent phase 3 trial.

Progression-free and overall survival rates were similar across treatment types, reported lead author Hiroyuki Nomura, MD, of Keio University, Tokyo, and his colleagues. The findings maintain doxorubicin/cisplatin as standard therapy; however, taxane/platinum chemotherapy could be a possible alternative for some patients because of similar efficacy and tolerability with a distinct toxicity profile.

“Establishment of evidence and validation of the optimal postoperative adjuvant chemotherapy regimen for endometrial cancer are important issues,” the investigators wrote in JAMA Oncology.

The multicenter, open-label study involved 788 patients with endometrial cancer at risk of progression, based on histologic findings. Eligibility required that patients have a residual tumor of at least 2 cm without extension beyond the abdominal cavity. Patients were randomly grouped into one of three treatment groups: doxorubicin/cisplatin, paclitaxel/carboplatin, or docetaxel/cisplatin. If tolerated, six 3-week cycles were given. The median follow-up period was 7 years. The primary and secondary endpoints were 5-year progression free survival and overall survival, respectively.

Survival rates were statistically similar between groups. The 5-year progression-free survival rate was 73.3% for doxorubicin/cisplatin, 73.9% for paclitaxel/carboplatin, and 79.0% for docetaxel/cisplatin (P = .12); the 5-year overall survival rate was 82.7% for doxorubicin/cisplatin, 86.1% for paclitaxel/carboplatin, and 88.1% for docetaxel/cisplatin (P = .67). Tolerability was also comparable, with a small range of discontinuation rates across treatment types, from 20.2% to 25.5% (P = .14).

“Although the superiority of docetaxel plus cisplatin and paclitaxel plus carboplatin over doxorubicin plus cisplatin was not demonstrated, we found that the three regimens were comparable in therapeutic effect,” the investigators concluded. “[C]onsidering efficacy and tolerability, taxane plus platinum regimens may be an alternative to treatment with doxorubicin plus cisplatin.”

The study was funded by a Health Labour Sciences Research Grant with nonspecific funding from AstraZeneca, Eisai, Bristol-Myers Squibb, and others. The investigators reported financial relationships with Chugai, Sanofi, Takeda, AbbVie, and others.

SOURCE: Nomura H et al. JAMA Oncol. 2019 Mar 21. doi: 10.1001/jamaoncol.2019.0001.

HONOLULU – The novel antibody-drug conjugate tisotumab vedotin (TV) shows encouraging activity and tolerability in heavily pretreated recurrent or metastatic cervical cancer, according to findings from the phase 1/2a innovaTV 201 trial.

Sharon Worcester/MDedge News

The investigator-assessed overall response rate (ORR) among 55 patients enrolled in the cervical cancer expansion portion of the study was 35%, and the confirmed response rate was 22%, including one complete response lasting 46 weeks, David S. Hong, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The median duration of response in confirmed responders was 6 months, median progression-free survival (PFS) was 4.1 months, and 6-month PFS was 40%, said Dr. Hong, deputy chair, department of investigational cancer therapeutics, division of cancer medicine, the University of Texas MD Anderson Cancer Center, Houston.

“Overall, the independent review and investigator review were highly correlated,” he noted.

Study participants had recurrent or metastatic cervical cancer that progressed on standard therapy, and Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1. Most had received at least two prior therapies.

As established in the phase 1 dose-escalation portion of the study, TV in the expansion phase was given at a dose of 2 mg/kg every 3 weeks until disease progression, toxicity, or withdrawal.

Median follow-up was 3.5 months and the median number of doses received was four; the treatment had acceptable tolerability, Dr. Hong said, noting that no treatment-related deaths occurred, and only 13% of patients had a dose reduction caused by an adverse event (AE).

The most common AE occurring in more than 20% of patients was epistaxis; most cases were grade 1. AEs of special interest and possibly related to the TV mechanism of action included neuropathy, bleeding-related events, and ocular events.

While there were a few cases of vaginal bleeding, they were believed to be caused by underlying disease, he noted.

The ocular events noted early in phase 1 of the study included mainly dry eyes and conjunctivitis, but a plan to mitigate these events, which involved the use of steroid eye drops, cooling eye masks, and dose reductions, reduced their incidence.

There were no grade 4 or 5 adverse events related to the agent, he said, noting that most patients came off study because of disease progression.

The prognosis for recurrent or metastatic cervical cancer is very poor, with a 5-year survival rate of only about 17%, Dr. Hong said, adding that data on the overall response and survival after the first line of therapy are somewhat limited.

Pembrolizumab (Keytruda) received Food and Drug Administration approval based on second-line setting data from the Keynote-158 trial showing a median ORR of just 14% and median PFS of just 2.1 months in programmed death-ligand 1–positive cervical cancer, he noted.

“Tissue factor (TF) is a protein expressed in cervical cancer, as well as ... a broad range of solid tumors. It is associated with high tumor stage, metastasis, and poor prognosis,” he explained. “TV is a first-in-class antibody-drug conjugate that’s a fully human monoclonal antibody targeting tissue factor.”

The drug, which has multiple mechanisms of action, is conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. Findings regarding its safety and tolerability in cervical cancer and a number of other tumors were published recently in The Lancet.

Dr. Hong’s presentation focused on the cervical cancer cohort.

The median PFS in innovaTV 201 compares favorably with that for pembrolizumab and supports continued investigation of TV, he said, noting that phase 2 studies of TV alone and in combination with other agents for recurrent or metastatic cervical cancer, as well as for platinum-resistant ovarian cancer, are ongoing.

The innovaTV 201 trial is sponsored by Genmab A/S. Dr. Hong reported having no disclosures.

[email protected]

SOURCE: Hong DS et al. SGO 2019, Abstract 19.

HONOLULU – The novel antibody-drug conjugate tisotumab vedotin (TV) shows encouraging activity and tolerability in heavily pretreated recurrent or metastatic cervical cancer, according to findings from the phase 1/2a innovaTV 201 trial.

Sharon Worcester/MDedge News

The investigator-assessed overall response rate (ORR) among 55 patients enrolled in the cervical cancer expansion portion of the study was 35%, and the confirmed response rate was 22%, including one complete response lasting 46 weeks, David S. Hong, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The median duration of response in confirmed responders was 6 months, median progression-free survival (PFS) was 4.1 months, and 6-month PFS was 40%, said Dr. Hong, deputy chair, department of investigational cancer therapeutics, division of cancer medicine, the University of Texas MD Anderson Cancer Center, Houston.

“Overall, the independent review and investigator review were highly correlated,” he noted.

Study participants had recurrent or metastatic cervical cancer that progressed on standard therapy, and Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1. Most had received at least two prior therapies.

As established in the phase 1 dose-escalation portion of the study, TV in the expansion phase was given at a dose of 2 mg/kg every 3 weeks until disease progression, toxicity, or withdrawal.

Median follow-up was 3.5 months and the median number of doses received was four; the treatment had acceptable tolerability, Dr. Hong said, noting that no treatment-related deaths occurred, and only 13% of patients had a dose reduction caused by an adverse event (AE).

The most common AE occurring in more than 20% of patients was epistaxis; most cases were grade 1. AEs of special interest and possibly related to the TV mechanism of action included neuropathy, bleeding-related events, and ocular events.

While there were a few cases of vaginal bleeding, they were believed to be caused by underlying disease, he noted.

The ocular events noted early in phase 1 of the study included mainly dry eyes and conjunctivitis, but a plan to mitigate these events, which involved the use of steroid eye drops, cooling eye masks, and dose reductions, reduced their incidence.

There were no grade 4 or 5 adverse events related to the agent, he said, noting that most patients came off study because of disease progression.

The prognosis for recurrent or metastatic cervical cancer is very poor, with a 5-year survival rate of only about 17%, Dr. Hong said, adding that data on the overall response and survival after the first line of therapy are somewhat limited.

Pembrolizumab (Keytruda) received Food and Drug Administration approval based on second-line setting data from the Keynote-158 trial showing a median ORR of just 14% and median PFS of just 2.1 months in programmed death-ligand 1–positive cervical cancer, he noted.

“Tissue factor (TF) is a protein expressed in cervical cancer, as well as ... a broad range of solid tumors. It is associated with high tumor stage, metastasis, and poor prognosis,” he explained. “TV is a first-in-class antibody-drug conjugate that’s a fully human monoclonal antibody targeting tissue factor.”

The drug, which has multiple mechanisms of action, is conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. Findings regarding its safety and tolerability in cervical cancer and a number of other tumors were published recently in The Lancet.

Dr. Hong’s presentation focused on the cervical cancer cohort.

The median PFS in innovaTV 201 compares favorably with that for pembrolizumab and supports continued investigation of TV, he said, noting that phase 2 studies of TV alone and in combination with other agents for recurrent or metastatic cervical cancer, as well as for platinum-resistant ovarian cancer, are ongoing.

The innovaTV 201 trial is sponsored by Genmab A/S. Dr. Hong reported having no disclosures.

[email protected]

SOURCE: Hong DS et al. SGO 2019, Abstract 19.

HONOLULU – The novel antibody-drug conjugate tisotumab vedotin (TV) shows encouraging activity and tolerability in heavily pretreated recurrent or metastatic cervical cancer, according to findings from the phase 1/2a innovaTV 201 trial.

Sharon Worcester/MDedge News

The investigator-assessed overall response rate (ORR) among 55 patients enrolled in the cervical cancer expansion portion of the study was 35%, and the confirmed response rate was 22%, including one complete response lasting 46 weeks, David S. Hong, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The median duration of response in confirmed responders was 6 months, median progression-free survival (PFS) was 4.1 months, and 6-month PFS was 40%, said Dr. Hong, deputy chair, department of investigational cancer therapeutics, division of cancer medicine, the University of Texas MD Anderson Cancer Center, Houston.

“Overall, the independent review and investigator review were highly correlated,” he noted.

Study participants had recurrent or metastatic cervical cancer that progressed on standard therapy, and Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1. Most had received at least two prior therapies.

As established in the phase 1 dose-escalation portion of the study, TV in the expansion phase was given at a dose of 2 mg/kg every 3 weeks until disease progression, toxicity, or withdrawal.

Median follow-up was 3.5 months and the median number of doses received was four; the treatment had acceptable tolerability, Dr. Hong said, noting that no treatment-related deaths occurred, and only 13% of patients had a dose reduction caused by an adverse event (AE).

The most common AE occurring in more than 20% of patients was epistaxis; most cases were grade 1. AEs of special interest and possibly related to the TV mechanism of action included neuropathy, bleeding-related events, and ocular events.

While there were a few cases of vaginal bleeding, they were believed to be caused by underlying disease, he noted.

The ocular events noted early in phase 1 of the study included mainly dry eyes and conjunctivitis, but a plan to mitigate these events, which involved the use of steroid eye drops, cooling eye masks, and dose reductions, reduced their incidence.

There were no grade 4 or 5 adverse events related to the agent, he said, noting that most patients came off study because of disease progression.

The prognosis for recurrent or metastatic cervical cancer is very poor, with a 5-year survival rate of only about 17%, Dr. Hong said, adding that data on the overall response and survival after the first line of therapy are somewhat limited.

Pembrolizumab (Keytruda) received Food and Drug Administration approval based on second-line setting data from the Keynote-158 trial showing a median ORR of just 14% and median PFS of just 2.1 months in programmed death-ligand 1–positive cervical cancer, he noted.

“Tissue factor (TF) is a protein expressed in cervical cancer, as well as ... a broad range of solid tumors. It is associated with high tumor stage, metastasis, and poor prognosis,” he explained. “TV is a first-in-class antibody-drug conjugate that’s a fully human monoclonal antibody targeting tissue factor.”

The drug, which has multiple mechanisms of action, is conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. Findings regarding its safety and tolerability in cervical cancer and a number of other tumors were published recently in The Lancet.

Dr. Hong’s presentation focused on the cervical cancer cohort.

The median PFS in innovaTV 201 compares favorably with that for pembrolizumab and supports continued investigation of TV, he said, noting that phase 2 studies of TV alone and in combination with other agents for recurrent or metastatic cervical cancer, as well as for platinum-resistant ovarian cancer, are ongoing.

The innovaTV 201 trial is sponsored by Genmab A/S. Dr. Hong reported having no disclosures.

[email protected]

SOURCE: Hong DS et al. SGO 2019, Abstract 19.

HONOLULU – Increasing access to brachytherapy for black patients with locally advanced cervical cancer may reduce racial disparities in survival, according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Stephanie Alimena, MD, of Brigham and Women’s Hospital in Boston, presented a large, retrospective study showing that use of brachytherapy mediated survival differences by race.

In the absence of brachytherapy, black patients had a significantly higher risk of death than did non-black patients (P = .013). However, when brachytherapy was used, black and non-black patients had a similar risk of death (P = .83).

“[W]e know that use of a brachytherapy boost is associated with improved patient outcomes, including improved cancer-specific and overall survival,” Dr. Alimena said. “We also know that African-American women have one of the highest incidences of cervical cancer in the United States and also have worse mortality from cervical cancer.”

“Studies have reached varying conclusions about the impact of race on brachytherapy utilization, with several smaller studies suggesting that minority women may be less likely to receive brachytherapy services compared to white women. No studies have specifically examined the interaction between race, radiation, and survival.”

Dr. Alimena and her colleagues decided to examine the interaction using data from the National Cancer Database. The researchers evaluated 15,411 women diagnosed with cervical cancer from 2004 to 2014. The patients had stage IB2 to IVA disease, their mean age was 54 years (range, 19-90), 58% had received brachytherapy, and 19% were black.

“Race was defined as black or non-black race, given that previous data had shown similar and even increased survival rates for Hispanic and Asian-American women compared to white patients diagnosed with cervical cancer,” Dr. Alimena noted.

Differences by race

The researchers found that black patients were significantly less likely to receive brachytherapy than were non-black patients: 52.5% vs. 59.0%, respectively (P less than .001).

Black patients were significantly more likely to have stage III disease (42.7% vs. 37.6%; P less than .001) and less likely to have stage IVA disease (6.8% vs. 7.3%; P less than .001).

Black patients were significantly more likely to have government insurance (57.0% vs. 49.1%; P less than .001) and less likely to have private insurance (27.6% vs. 36.7%; P less than .001).

And black patients were significantly more likely to have annual incomes below $38,000 (49.4% vs. 22.6%; P less than .001).
 

Factors associated with brachytherapy

In a multivariate analysis, black race was significantly associated with a reduced likelihood of receiving brachytherapy. The odds ratio (OR) was 0.86 (P = .003).

Other factors significantly associated with a reduced likelihood of receiving brachytherapy were:

• Being older than 70 years (OR = 0.59; P less than .001)
• Having government insurance (OR = 0.89; P = .008) or no insurance/unknown insurance status (OR = 0.75; P less than .001)
• Having stage III disease (OR = 0.47; P less than .001) or stage IVA disease (OR = 0.20; P less than .001)
• Being treated in southern states (OR = 0.67; P less than .001) or western states (OR = 0.86; P = .02)
• Having a Charlson/Deyo score of 2 or more (OR = 0.73; P less than .001).

Race, brachytherapy, and survival

“Consistent with prior data, we found that black patients had a significant decrease in overall survival, compared to non-black women,” Dr. Alimena said. “Furthermore, we found survival differences by race were mediated by brachytherapy use.”

The median overall survival was 52.5 months among black patients and 65.3 months among non-black patients (P less than .001).

Among patients who did not receive brachytherapy, black patients had a significantly higher risk of death than non-black patients (adjusted hazard ratio = 1.11; P = .013).

However, among patients who did receive brachytherapy, black and non-black patients had a similar risk of death (adjusted hazard ratio = 1.01; P = .83). The interaction term comparing these survival curves was statistically significant (P = .043).

“This is the first study, to our knowledge, to show such an interaction between race and survival being mediated by one particular treatment modality,” Dr. Alimena said.

“While not directly tested in this study, the most likely hypothesis why black patients may be less likely to receive brachytherapy is having poor access to brachytherapy services. This suggests that reducing racial disparities in survival is possible by increasing access to brachytherapy for black patients.”

Dr. Alimena had no financial disclosures.

[email protected]

SOURCE: Alimena S et al. SGO 2019. Abstract 11.

HONOLULU – Increasing access to brachytherapy for black patients with locally advanced cervical cancer may reduce racial disparities in survival, according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Stephanie Alimena, MD, of Brigham and Women’s Hospital in Boston, presented a large, retrospective study showing that use of brachytherapy mediated survival differences by race.

In the absence of brachytherapy, black patients had a significantly higher risk of death than did non-black patients (P = .013). However, when brachytherapy was used, black and non-black patients had a similar risk of death (P = .83).

“[W]e know that use of a brachytherapy boost is associated with improved patient outcomes, including improved cancer-specific and overall survival,” Dr. Alimena said. “We also know that African-American women have one of the highest incidences of cervical cancer in the United States and also have worse mortality from cervical cancer.”

“Studies have reached varying conclusions about the impact of race on brachytherapy utilization, with several smaller studies suggesting that minority women may be less likely to receive brachytherapy services compared to white women. No studies have specifically examined the interaction between race, radiation, and survival.”

Dr. Alimena and her colleagues decided to examine the interaction using data from the National Cancer Database. The researchers evaluated 15,411 women diagnosed with cervical cancer from 2004 to 2014. The patients had stage IB2 to IVA disease, their mean age was 54 years (range, 19-90), 58% had received brachytherapy, and 19% were black.

“Race was defined as black or non-black race, given that previous data had shown similar and even increased survival rates for Hispanic and Asian-American women compared to white patients diagnosed with cervical cancer,” Dr. Alimena noted.

Differences by race

The researchers found that black patients were significantly less likely to receive brachytherapy than were non-black patients: 52.5% vs. 59.0%, respectively (P less than .001).

Black patients were significantly more likely to have stage III disease (42.7% vs. 37.6%; P less than .001) and less likely to have stage IVA disease (6.8% vs. 7.3%; P less than .001).

Black patients were significantly more likely to have government insurance (57.0% vs. 49.1%; P less than .001) and less likely to have private insurance (27.6% vs. 36.7%; P less than .001).

And black patients were significantly more likely to have annual incomes below $38,000 (49.4% vs. 22.6%; P less than .001).
 

Factors associated with brachytherapy

In a multivariate analysis, black race was significantly associated with a reduced likelihood of receiving brachytherapy. The odds ratio (OR) was 0.86 (P = .003).

Other factors significantly associated with a reduced likelihood of receiving brachytherapy were:

• Being older than 70 years (OR = 0.59; P less than .001)
• Having government insurance (OR = 0.89; P = .008) or no insurance/unknown insurance status (OR = 0.75; P less than .001)
• Having stage III disease (OR = 0.47; P less than .001) or stage IVA disease (OR = 0.20; P less than .001)
• Being treated in southern states (OR = 0.67; P less than .001) or western states (OR = 0.86; P = .02)
• Having a Charlson/Deyo score of 2 or more (OR = 0.73; P less than .001).

Race, brachytherapy, and survival

“Consistent with prior data, we found that black patients had a significant decrease in overall survival, compared to non-black women,” Dr. Alimena said. “Furthermore, we found survival differences by race were mediated by brachytherapy use.”

The median overall survival was 52.5 months among black patients and 65.3 months among non-black patients (P less than .001).

Among patients who did not receive brachytherapy, black patients had a significantly higher risk of death than non-black patients (adjusted hazard ratio = 1.11; P = .013).

However, among patients who did receive brachytherapy, black and non-black patients had a similar risk of death (adjusted hazard ratio = 1.01; P = .83). The interaction term comparing these survival curves was statistically significant (P = .043).

“This is the first study, to our knowledge, to show such an interaction between race and survival being mediated by one particular treatment modality,” Dr. Alimena said.

“While not directly tested in this study, the most likely hypothesis why black patients may be less likely to receive brachytherapy is having poor access to brachytherapy services. This suggests that reducing racial disparities in survival is possible by increasing access to brachytherapy for black patients.”

Dr. Alimena had no financial disclosures.

[email protected]

SOURCE: Alimena S et al. SGO 2019. Abstract 11.

HONOLULU – Increasing access to brachytherapy for black patients with locally advanced cervical cancer may reduce racial disparities in survival, according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Stephanie Alimena, MD, of Brigham and Women’s Hospital in Boston, presented a large, retrospective study showing that use of brachytherapy mediated survival differences by race.

In the absence of brachytherapy, black patients had a significantly higher risk of death than did non-black patients (P = .013). However, when brachytherapy was used, black and non-black patients had a similar risk of death (P = .83).

“[W]e know that use of a brachytherapy boost is associated with improved patient outcomes, including improved cancer-specific and overall survival,” Dr. Alimena said. “We also know that African-American women have one of the highest incidences of cervical cancer in the United States and also have worse mortality from cervical cancer.”

“Studies have reached varying conclusions about the impact of race on brachytherapy utilization, with several smaller studies suggesting that minority women may be less likely to receive brachytherapy services compared to white women. No studies have specifically examined the interaction between race, radiation, and survival.”

Dr. Alimena and her colleagues decided to examine the interaction using data from the National Cancer Database. The researchers evaluated 15,411 women diagnosed with cervical cancer from 2004 to 2014. The patients had stage IB2 to IVA disease, their mean age was 54 years (range, 19-90), 58% had received brachytherapy, and 19% were black.

“Race was defined as black or non-black race, given that previous data had shown similar and even increased survival rates for Hispanic and Asian-American women compared to white patients diagnosed with cervical cancer,” Dr. Alimena noted.

Differences by race

The researchers found that black patients were significantly less likely to receive brachytherapy than were non-black patients: 52.5% vs. 59.0%, respectively (P less than .001).

Black patients were significantly more likely to have stage III disease (42.7% vs. 37.6%; P less than .001) and less likely to have stage IVA disease (6.8% vs. 7.3%; P less than .001).

Black patients were significantly more likely to have government insurance (57.0% vs. 49.1%; P less than .001) and less likely to have private insurance (27.6% vs. 36.7%; P less than .001).

And black patients were significantly more likely to have annual incomes below $38,000 (49.4% vs. 22.6%; P less than .001).
 

Factors associated with brachytherapy

In a multivariate analysis, black race was significantly associated with a reduced likelihood of receiving brachytherapy. The odds ratio (OR) was 0.86 (P = .003).

Other factors significantly associated with a reduced likelihood of receiving brachytherapy were:

• Being older than 70 years (OR = 0.59; P less than .001)
• Having government insurance (OR = 0.89; P = .008) or no insurance/unknown insurance status (OR = 0.75; P less than .001)
• Having stage III disease (OR = 0.47; P less than .001) or stage IVA disease (OR = 0.20; P less than .001)
• Being treated in southern states (OR = 0.67; P less than .001) or western states (OR = 0.86; P = .02)
• Having a Charlson/Deyo score of 2 or more (OR = 0.73; P less than .001).

Race, brachytherapy, and survival

“Consistent with prior data, we found that black patients had a significant decrease in overall survival, compared to non-black women,” Dr. Alimena said. “Furthermore, we found survival differences by race were mediated by brachytherapy use.”

The median overall survival was 52.5 months among black patients and 65.3 months among non-black patients (P less than .001).

Among patients who did not receive brachytherapy, black patients had a significantly higher risk of death than non-black patients (adjusted hazard ratio = 1.11; P = .013).

However, among patients who did receive brachytherapy, black and non-black patients had a similar risk of death (adjusted hazard ratio = 1.01; P = .83). The interaction term comparing these survival curves was statistically significant (P = .043).

“This is the first study, to our knowledge, to show such an interaction between race and survival being mediated by one particular treatment modality,” Dr. Alimena said.

“While not directly tested in this study, the most likely hypothesis why black patients may be less likely to receive brachytherapy is having poor access to brachytherapy services. This suggests that reducing racial disparities in survival is possible by increasing access to brachytherapy for black patients.”

Dr. Alimena had no financial disclosures.

[email protected]

SOURCE: Alimena S et al. SGO 2019. Abstract 11.

HONOLULU – Adding trabectedin to pegylated liposomal doxorubicin (PLD) significantly prolongs overall and progression-free survival in BRCA1/2-mutated patients with advanced-relapsed epithelial ovarian cancer after two prior lines of platinum-based therapy, according to prespecified subgroup analyses of a randomized, open-label, phase 3 trial.

Patients with a platinum-free interval (PFI) of 6-12 months also experienced significantly improved progression-free survival (PFS), and those with both a BRCA mutation and PFI of 6-12 months experienced significantly improved overall survival (OS) and PFS with combined trabectedin and PLD vs. PLD alone, Bradley J. Monk, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Of 576 patients enrolled in the ET743-OVC-3006 trial, 289 received the combination regimen, and 287 received PLD alone. The study completed enrollment but was discontinued on January 18, 2018, after an interim analysis showed the futility threshold for OS and observed toxicity in the combination therapy group was exceeded.

OS was 21.5 and 22.2 months (hazard ratio = 1.13) in the combination and monotherapy groups, respectively. However, the subgroups analysis of patients with a germline BRCA1/2 mutation showed a median OS of 34.2 months with combination therapy and 20.9 months with PLD monotherapy, for a median survival benefit with combination therapy of 13.3 months (HR = 0.54), said Dr. Monk, professor and director of the division of gynecologic oncology at Creighton University School of Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, Ariz.

A subgroup of 60 patients with both a BRCA mutation and a PFI of 6-12 months had even greater improvement in OS with combination therapy when compared with PLD monotherapy (31.5 vs. 14.9 months; HR = 0.37). An effect on PFS was also detected in this subgroup (10.1 vs. 6.1 months; HR = 0.48), he said.

No difference in PFS was found in the overall unselected study population, Dr. Monk said, but among all patients with 6-12-month PFI alone, combination therapy led to significantly longer PFS than with monotherapy (7.5 vs. 5.5 months; HR = 0.72, P = .0388) and a positive trend in OS for the combination group (24.8 vs. 17.4 months; HR = 0.69; P = .565).

“I get it – this suffers from multiple comparisons, and this [analysis] in particular was ad hoc,” he said.

Still, given historical findings with respect to trabectedin in combination with PLD, the findings are provocative, he said.

Trabectedin is “a complicated anticancer cytotoxic medication” approved by the Food and Drug Administration in 2015 based on findings of treatment benefit in liposarcoma and leiomyosarcoma (including uterine leiomyosarcoma), he explained.

The agent has also been studied widely in other tumors, including in ovarian cancer. In the OVA-301 trial, for example, Dr. Monk and his colleagues looked at trabectedin in the second-line setting in patients with recurrent ovarian cancer.

That trial, which met its primary endpoint of an overall PFS benefit with trabectedin and generated the hypothesis that the agent might have particular benefit in BRCA-mutated patients, led to regulatory approval of trabectedin in Europe and elsewhere as an option for treatment in patients with partially platinum-sensitive recurrences – but not in the United States, he said.

Since OVA-301 did not lead to FDA approval, he and his colleagues designed the current study to look more closely at trabectedin with and without PLD, using the same dosing regimens as in OVA-301, but in the third-line setting and using OS as the primary endpoint.

Based on the intriguing OVA-301 findings in BRCA-mutated patients, the BRCA1/2-mutated subgroup analysis in the ET743-OVC-3006 trial was prespecified, he noted.

Study participants were women with advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer who responded to two prior lines of platinum-based therapy and who were at least 6 months platinum-free. They were randomly assigned 1:1 to trabectedin plus PLD or PLD alone. Dosing in the combination arm was 1.1 mg/m² of intravenous trabectedin over 3 hours and 30 mg/m² of IV PLD given over 90 minutes every 3 weeks, and in the monotherapy arm PLD was given at a dose of 50 mg/m² IV over 90 minutes every 4 weeks.

The groups were well balanced with respect to age, race, and performance status, and each included “a smattering of histological subtypes,” he said.

Of the 576 enrolled, 155 were BRCA1 or BRCA2-positive, with about two-thirds carrying a BRCA1 mutation.

Very few were exposed to bevacizumab or poly(ADP ribose) polymerase (PARP) inhibitors, as the study was initiated before those were developed.

Adverse events (AEs) of all grades occurred at similar rates in the two arms and occurred in most patients. Most were drug-related, but grade 3-4 AE rates were higher in the combination arm (79% vs. 54%). Drug-related AEs leading to treatment discontinuation occurred in 32.5% and 16% of the combination and monotherapy arm patients, respectively, Dr. Monk said.

“Most of those treatment-related AEs were cytopenia and/or transaminitis. There were also almost twice as many deaths in the combination arm: 3.5% vs. 1.6%,” he said, adding that the deaths were thought to be related to tumor progression rather than to the drugs.

Although the addition of trabectedin to PLD did not prolong OS, compared with PLD alone in unselected patients with advanced, third-line, recurrent ovarian cancer, the combination does appear to benefit patients with germline BRCA mutations, a 6-12 month platinum-free interval, or both, he said, concluding that “the results of this phase 3 subanalysis are consistent with the previous observations in OVA-301 that trabectedin alone or with PLD displays selective antitumor activity in this BRCA subgroup.

“It adds more toxicity, but no new safety signals were identified,” he added.

Asked during a panel discussion if he thinks these results mark “then end of the road” for trabectedin, Dr. Monk said he does not.

“I don’t think we should be penalized because we enrolled all those non-BRCA patients. When you look at the BRCA cohort I think there is an opportunity to get this to our patients,” he said, noting that “the major challenge” is that those patients had not been given a PARP inhibitor. “So I think that there might be an opportunity for licensing, but the confirmatory trial would have to [look at whether] the drug still works after failure of a PARP.”

The ET743-OVC-3006 trial was sponsored by Janssen Research & Development. Dr. Monk reported financial relationships (consulting, honoraria/reimbursement, and/or speaker’s bureau participation) with Janssen/Johnson & Johnson and more than 20 other pharmaceutical companies.

[email protected]

SOURCE: Monk B et al., SGO 2019: Abstract 20.

HONOLULU – Adding trabectedin to pegylated liposomal doxorubicin (PLD) significantly prolongs overall and progression-free survival in BRCA1/2-mutated patients with advanced-relapsed epithelial ovarian cancer after two prior lines of platinum-based therapy, according to prespecified subgroup analyses of a randomized, open-label, phase 3 trial.

Patients with a platinum-free interval (PFI) of 6-12 months also experienced significantly improved progression-free survival (PFS), and those with both a BRCA mutation and PFI of 6-12 months experienced significantly improved overall survival (OS) and PFS with combined trabectedin and PLD vs. PLD alone, Bradley J. Monk, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Of 576 patients enrolled in the ET743-OVC-3006 trial, 289 received the combination regimen, and 287 received PLD alone. The study completed enrollment but was discontinued on January 18, 2018, after an interim analysis showed the futility threshold for OS and observed toxicity in the combination therapy group was exceeded.

OS was 21.5 and 22.2 months (hazard ratio = 1.13) in the combination and monotherapy groups, respectively. However, the subgroups analysis of patients with a germline BRCA1/2 mutation showed a median OS of 34.2 months with combination therapy and 20.9 months with PLD monotherapy, for a median survival benefit with combination therapy of 13.3 months (HR = 0.54), said Dr. Monk, professor and director of the division of gynecologic oncology at Creighton University School of Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, Ariz.

A subgroup of 60 patients with both a BRCA mutation and a PFI of 6-12 months had even greater improvement in OS with combination therapy when compared with PLD monotherapy (31.5 vs. 14.9 months; HR = 0.37). An effect on PFS was also detected in this subgroup (10.1 vs. 6.1 months; HR = 0.48), he said.

No difference in PFS was found in the overall unselected study population, Dr. Monk said, but among all patients with 6-12-month PFI alone, combination therapy led to significantly longer PFS than with monotherapy (7.5 vs. 5.5 months; HR = 0.72, P = .0388) and a positive trend in OS for the combination group (24.8 vs. 17.4 months; HR = 0.69; P = .565).

“I get it – this suffers from multiple comparisons, and this [analysis] in particular was ad hoc,” he said.

Still, given historical findings with respect to trabectedin in combination with PLD, the findings are provocative, he said.

Trabectedin is “a complicated anticancer cytotoxic medication” approved by the Food and Drug Administration in 2015 based on findings of treatment benefit in liposarcoma and leiomyosarcoma (including uterine leiomyosarcoma), he explained.

The agent has also been studied widely in other tumors, including in ovarian cancer. In the OVA-301 trial, for example, Dr. Monk and his colleagues looked at trabectedin in the second-line setting in patients with recurrent ovarian cancer.

That trial, which met its primary endpoint of an overall PFS benefit with trabectedin and generated the hypothesis that the agent might have particular benefit in BRCA-mutated patients, led to regulatory approval of trabectedin in Europe and elsewhere as an option for treatment in patients with partially platinum-sensitive recurrences – but not in the United States, he said.

Since OVA-301 did not lead to FDA approval, he and his colleagues designed the current study to look more closely at trabectedin with and without PLD, using the same dosing regimens as in OVA-301, but in the third-line setting and using OS as the primary endpoint.

Based on the intriguing OVA-301 findings in BRCA-mutated patients, the BRCA1/2-mutated subgroup analysis in the ET743-OVC-3006 trial was prespecified, he noted.

Study participants were women with advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer who responded to two prior lines of platinum-based therapy and who were at least 6 months platinum-free. They were randomly assigned 1:1 to trabectedin plus PLD or PLD alone. Dosing in the combination arm was 1.1 mg/m² of intravenous trabectedin over 3 hours and 30 mg/m² of IV PLD given over 90 minutes every 3 weeks, and in the monotherapy arm PLD was given at a dose of 50 mg/m² IV over 90 minutes every 4 weeks.

The groups were well balanced with respect to age, race, and performance status, and each included “a smattering of histological subtypes,” he said.

Of the 576 enrolled, 155 were BRCA1 or BRCA2-positive, with about two-thirds carrying a BRCA1 mutation.

Very few were exposed to bevacizumab or poly(ADP ribose) polymerase (PARP) inhibitors, as the study was initiated before those were developed.

Adverse events (AEs) of all grades occurred at similar rates in the two arms and occurred in most patients. Most were drug-related, but grade 3-4 AE rates were higher in the combination arm (79% vs. 54%). Drug-related AEs leading to treatment discontinuation occurred in 32.5% and 16% of the combination and monotherapy arm patients, respectively, Dr. Monk said.

“Most of those treatment-related AEs were cytopenia and/or transaminitis. There were also almost twice as many deaths in the combination arm: 3.5% vs. 1.6%,” he said, adding that the deaths were thought to be related to tumor progression rather than to the drugs.

Although the addition of trabectedin to PLD did not prolong OS, compared with PLD alone in unselected patients with advanced, third-line, recurrent ovarian cancer, the combination does appear to benefit patients with germline BRCA mutations, a 6-12 month platinum-free interval, or both, he said, concluding that “the results of this phase 3 subanalysis are consistent with the previous observations in OVA-301 that trabectedin alone or with PLD displays selective antitumor activity in this BRCA subgroup.

“It adds more toxicity, but no new safety signals were identified,” he added.

Asked during a panel discussion if he thinks these results mark “then end of the road” for trabectedin, Dr. Monk said he does not.

“I don’t think we should be penalized because we enrolled all those non-BRCA patients. When you look at the BRCA cohort I think there is an opportunity to get this to our patients,” he said, noting that “the major challenge” is that those patients had not been given a PARP inhibitor. “So I think that there might be an opportunity for licensing, but the confirmatory trial would have to [look at whether] the drug still works after failure of a PARP.”

The ET743-OVC-3006 trial was sponsored by Janssen Research & Development. Dr. Monk reported financial relationships (consulting, honoraria/reimbursement, and/or speaker’s bureau participation) with Janssen/Johnson & Johnson and more than 20 other pharmaceutical companies.

[email protected]

SOURCE: Monk B et al., SGO 2019: Abstract 20.

HONOLULU – Adding trabectedin to pegylated liposomal doxorubicin (PLD) significantly prolongs overall and progression-free survival in BRCA1/2-mutated patients with advanced-relapsed epithelial ovarian cancer after two prior lines of platinum-based therapy, according to prespecified subgroup analyses of a randomized, open-label, phase 3 trial.

Patients with a platinum-free interval (PFI) of 6-12 months also experienced significantly improved progression-free survival (PFS), and those with both a BRCA mutation and PFI of 6-12 months experienced significantly improved overall survival (OS) and PFS with combined trabectedin and PLD vs. PLD alone, Bradley J. Monk, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Of 576 patients enrolled in the ET743-OVC-3006 trial, 289 received the combination regimen, and 287 received PLD alone. The study completed enrollment but was discontinued on January 18, 2018, after an interim analysis showed the futility threshold for OS and observed toxicity in the combination therapy group was exceeded.

OS was 21.5 and 22.2 months (hazard ratio = 1.13) in the combination and monotherapy groups, respectively. However, the subgroups analysis of patients with a germline BRCA1/2 mutation showed a median OS of 34.2 months with combination therapy and 20.9 months with PLD monotherapy, for a median survival benefit with combination therapy of 13.3 months (HR = 0.54), said Dr. Monk, professor and director of the division of gynecologic oncology at Creighton University School of Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, Ariz.

A subgroup of 60 patients with both a BRCA mutation and a PFI of 6-12 months had even greater improvement in OS with combination therapy when compared with PLD monotherapy (31.5 vs. 14.9 months; HR = 0.37). An effect on PFS was also detected in this subgroup (10.1 vs. 6.1 months; HR = 0.48), he said.

No difference in PFS was found in the overall unselected study population, Dr. Monk said, but among all patients with 6-12-month PFI alone, combination therapy led to significantly longer PFS than with monotherapy (7.5 vs. 5.5 months; HR = 0.72, P = .0388) and a positive trend in OS for the combination group (24.8 vs. 17.4 months; HR = 0.69; P = .565).

“I get it – this suffers from multiple comparisons, and this [analysis] in particular was ad hoc,” he said.

Still, given historical findings with respect to trabectedin in combination with PLD, the findings are provocative, he said.

Trabectedin is “a complicated anticancer cytotoxic medication” approved by the Food and Drug Administration in 2015 based on findings of treatment benefit in liposarcoma and leiomyosarcoma (including uterine leiomyosarcoma), he explained.

The agent has also been studied widely in other tumors, including in ovarian cancer. In the OVA-301 trial, for example, Dr. Monk and his colleagues looked at trabectedin in the second-line setting in patients with recurrent ovarian cancer.

That trial, which met its primary endpoint of an overall PFS benefit with trabectedin and generated the hypothesis that the agent might have particular benefit in BRCA-mutated patients, led to regulatory approval of trabectedin in Europe and elsewhere as an option for treatment in patients with partially platinum-sensitive recurrences – but not in the United States, he said.

Since OVA-301 did not lead to FDA approval, he and his colleagues designed the current study to look more closely at trabectedin with and without PLD, using the same dosing regimens as in OVA-301, but in the third-line setting and using OS as the primary endpoint.

Based on the intriguing OVA-301 findings in BRCA-mutated patients, the BRCA1/2-mutated subgroup analysis in the ET743-OVC-3006 trial was prespecified, he noted.

Study participants were women with advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer who responded to two prior lines of platinum-based therapy and who were at least 6 months platinum-free. They were randomly assigned 1:1 to trabectedin plus PLD or PLD alone. Dosing in the combination arm was 1.1 mg/m² of intravenous trabectedin over 3 hours and 30 mg/m² of IV PLD given over 90 minutes every 3 weeks, and in the monotherapy arm PLD was given at a dose of 50 mg/m² IV over 90 minutes every 4 weeks.

The groups were well balanced with respect to age, race, and performance status, and each included “a smattering of histological subtypes,” he said.

Of the 576 enrolled, 155 were BRCA1 or BRCA2-positive, with about two-thirds carrying a BRCA1 mutation.

Very few were exposed to bevacizumab or poly(ADP ribose) polymerase (PARP) inhibitors, as the study was initiated before those were developed.

Adverse events (AEs) of all grades occurred at similar rates in the two arms and occurred in most patients. Most were drug-related, but grade 3-4 AE rates were higher in the combination arm (79% vs. 54%). Drug-related AEs leading to treatment discontinuation occurred in 32.5% and 16% of the combination and monotherapy arm patients, respectively, Dr. Monk said.

“Most of those treatment-related AEs were cytopenia and/or transaminitis. There were also almost twice as many deaths in the combination arm: 3.5% vs. 1.6%,” he said, adding that the deaths were thought to be related to tumor progression rather than to the drugs.

Although the addition of trabectedin to PLD did not prolong OS, compared with PLD alone in unselected patients with advanced, third-line, recurrent ovarian cancer, the combination does appear to benefit patients with germline BRCA mutations, a 6-12 month platinum-free interval, or both, he said, concluding that “the results of this phase 3 subanalysis are consistent with the previous observations in OVA-301 that trabectedin alone or with PLD displays selective antitumor activity in this BRCA subgroup.

“It adds more toxicity, but no new safety signals were identified,” he added.

Asked during a panel discussion if he thinks these results mark “then end of the road” for trabectedin, Dr. Monk said he does not.

“I don’t think we should be penalized because we enrolled all those non-BRCA patients. When you look at the BRCA cohort I think there is an opportunity to get this to our patients,” he said, noting that “the major challenge” is that those patients had not been given a PARP inhibitor. “So I think that there might be an opportunity for licensing, but the confirmatory trial would have to [look at whether] the drug still works after failure of a PARP.”

The ET743-OVC-3006 trial was sponsored by Janssen Research & Development. Dr. Monk reported financial relationships (consulting, honoraria/reimbursement, and/or speaker’s bureau participation) with Janssen/Johnson & Johnson and more than 20 other pharmaceutical companies.

[email protected]

SOURCE: Monk B et al., SGO 2019: Abstract 20.

HONOLULU – The combination of lenvatinib and paclitaxel was considered active and well tolerated in a phase 1 trial of patients with recurrent endometrial or ovarian cancer.

Daily lenvatinib plus weekly paclitaxel produced an objective response rate of 65% and a clinical benefit rate of 96%.

Most adverse events (AEs) were grade 1 to 2. The most common grade 3 or higher AEs were hypertension, cytopenias, fatigue, and diarrhea.

Floor J. Backes, MD, of the Ohio State University Comprehensive Cancer Center in Columbus presented these results at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The trial (NCT02788708) included 26 patients with a median age of 63 years (range, 45-74). All patients had adequate organ function and measurable disease.

Nineteen patients had ovarian cancer: 13 with high-grade serous, 2 with low-grade serous, 2 clear cell, 1 endometrioid, and 1 carcinosarcoma. Seven patients had endometrial cancer: 4 endometrioid and 3 serous.

The patients must have received at least one prior platinum-based therapy. In all, they had a median of 3 prior therapies (range, 1-5).

The patients received intravenous paclitaxel at 80 mg/m² on days 1, 8, and 15 of a 28-day cycle. They also received oral lenvatinib daily at doses of 8 mg (n = 4), 12 mg (n = 3), 16 mg (n = 13), or 20 mg (n = 6).

There were no dose-limiting toxicities (DLTs) in the 8-mg or 12-mg dose groups. There was one DLT (mucositis) at the 16-mg dose level, and two DLTs (hypertension and fatigue) occurred at the 20-mg dose level.

“[At 20 mg,] patients were unable to take more than 75% of the study drug during the first cycle, and that was considered a DLT,” Dr. Backes said. “So our recommended phase 2 dose was lenvatinib 16 mg daily and paclitaxel 80 mg.”

Safety

“Toxicities were fairly common,” Dr. Backes noted. “The majority of these were cytopenias, but we also saw some GI toxicity – mucositis, diarrhea, nausea – and the VEGF inhibitor–related toxicities that we’re familiar with – hypertension, proteinuria, epistaxis. Fortunately, the majority of toxicities were grade 1 to 2.”

The most common AEs of any grade were leukopenia (58%), anemia (50%), mucositis (46%), diarrhea (46%), lymphopenia (42%), anorexia (42%), hypertension (42%), fatigue (42%), nausea (35%), proteinuria (27%), epistaxis (27%), and hoarseness (27%).

Grade 3 or higher AEs included hypertension (19%), neutropenia (15%), leukopenia (12%), anemia (12%), lymphopenia (8%), fatigue (8%), diarrhea (8%), mucositis (4%), vomiting (4%), hematuria (4%), rash (4%), and thrombocytopenia (4%).

“There was one patient [4%] who had a bowel perforation – small bowel perforation – at the site of previous stenosis after multiple prior bowel surgeries,” Dr. Backes noted.

Efficacy

In the 23 evaluable patients, the objective response rate was 65%, and the clinical benefit rate was 96%. One patient had a complete response, 14 had partial responses, 7 had stable disease, and 1 progressed.

The median duration of response was 10.9 months, and the median progression-free survival was 14.0 months.

The objective response rate was 71% in patients with ovarian cancer and 50% in patients with endometrial cancer. The median progression-free survival in these groups was 14.0 months and 12.8 months, respectively.

Dr. Backes said these results suggest lenvatinib plus paclitaxel is safe and active in recurrent ovarian and endometrial cancer, but these findings must be confirmed in a larger study.

This was an investigator-initiated study supported by Eisai. Dr. Backes disclosed relationships with Eisai, ImmunoGen, Clovis Oncology, Tesaro, Merck, and Agenus.

[email protected]

SOURCE: Backes FJ et al. SGO 2019, Abstract LBA5.

HONOLULU – The combination of lenvatinib and paclitaxel was considered active and well tolerated in a phase 1 trial of patients with recurrent endometrial or ovarian cancer.

Daily lenvatinib plus weekly paclitaxel produced an objective response rate of 65% and a clinical benefit rate of 96%.

Most adverse events (AEs) were grade 1 to 2. The most common grade 3 or higher AEs were hypertension, cytopenias, fatigue, and diarrhea.

Floor J. Backes, MD, of the Ohio State University Comprehensive Cancer Center in Columbus presented these results at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The trial (NCT02788708) included 26 patients with a median age of 63 years (range, 45-74). All patients had adequate organ function and measurable disease.

Nineteen patients had ovarian cancer: 13 with high-grade serous, 2 with low-grade serous, 2 clear cell, 1 endometrioid, and 1 carcinosarcoma. Seven patients had endometrial cancer: 4 endometrioid and 3 serous.

The patients must have received at least one prior platinum-based therapy. In all, they had a median of 3 prior therapies (range, 1-5).

The patients received intravenous paclitaxel at 80 mg/m² on days 1, 8, and 15 of a 28-day cycle. They also received oral lenvatinib daily at doses of 8 mg (n = 4), 12 mg (n = 3), 16 mg (n = 13), or 20 mg (n = 6).

There were no dose-limiting toxicities (DLTs) in the 8-mg or 12-mg dose groups. There was one DLT (mucositis) at the 16-mg dose level, and two DLTs (hypertension and fatigue) occurred at the 20-mg dose level.

“[At 20 mg,] patients were unable to take more than 75% of the study drug during the first cycle, and that was considered a DLT,” Dr. Backes said. “So our recommended phase 2 dose was lenvatinib 16 mg daily and paclitaxel 80 mg.”

Safety

“Toxicities were fairly common,” Dr. Backes noted. “The majority of these were cytopenias, but we also saw some GI toxicity – mucositis, diarrhea, nausea – and the VEGF inhibitor–related toxicities that we’re familiar with – hypertension, proteinuria, epistaxis. Fortunately, the majority of toxicities were grade 1 to 2.”

The most common AEs of any grade were leukopenia (58%), anemia (50%), mucositis (46%), diarrhea (46%), lymphopenia (42%), anorexia (42%), hypertension (42%), fatigue (42%), nausea (35%), proteinuria (27%), epistaxis (27%), and hoarseness (27%).

Grade 3 or higher AEs included hypertension (19%), neutropenia (15%), leukopenia (12%), anemia (12%), lymphopenia (8%), fatigue (8%), diarrhea (8%), mucositis (4%), vomiting (4%), hematuria (4%), rash (4%), and thrombocytopenia (4%).

“There was one patient [4%] who had a bowel perforation – small bowel perforation – at the site of previous stenosis after multiple prior bowel surgeries,” Dr. Backes noted.

Efficacy

In the 23 evaluable patients, the objective response rate was 65%, and the clinical benefit rate was 96%. One patient had a complete response, 14 had partial responses, 7 had stable disease, and 1 progressed.

The median duration of response was 10.9 months, and the median progression-free survival was 14.0 months.

The objective response rate was 71% in patients with ovarian cancer and 50% in patients with endometrial cancer. The median progression-free survival in these groups was 14.0 months and 12.8 months, respectively.

Dr. Backes said these results suggest lenvatinib plus paclitaxel is safe and active in recurrent ovarian and endometrial cancer, but these findings must be confirmed in a larger study.

This was an investigator-initiated study supported by Eisai. Dr. Backes disclosed relationships with Eisai, ImmunoGen, Clovis Oncology, Tesaro, Merck, and Agenus.

[email protected]

SOURCE: Backes FJ et al. SGO 2019, Abstract LBA5.

HONOLULU – The combination of lenvatinib and paclitaxel was considered active and well tolerated in a phase 1 trial of patients with recurrent endometrial or ovarian cancer.

Daily lenvatinib plus weekly paclitaxel produced an objective response rate of 65% and a clinical benefit rate of 96%.

Most adverse events (AEs) were grade 1 to 2. The most common grade 3 or higher AEs were hypertension, cytopenias, fatigue, and diarrhea.

Floor J. Backes, MD, of the Ohio State University Comprehensive Cancer Center in Columbus presented these results at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The trial (NCT02788708) included 26 patients with a median age of 63 years (range, 45-74). All patients had adequate organ function and measurable disease.

Nineteen patients had ovarian cancer: 13 with high-grade serous, 2 with low-grade serous, 2 clear cell, 1 endometrioid, and 1 carcinosarcoma. Seven patients had endometrial cancer: 4 endometrioid and 3 serous.

The patients must have received at least one prior platinum-based therapy. In all, they had a median of 3 prior therapies (range, 1-5).

The patients received intravenous paclitaxel at 80 mg/m² on days 1, 8, and 15 of a 28-day cycle. They also received oral lenvatinib daily at doses of 8 mg (n = 4), 12 mg (n = 3), 16 mg (n = 13), or 20 mg (n = 6).

There were no dose-limiting toxicities (DLTs) in the 8-mg or 12-mg dose groups. There was one DLT (mucositis) at the 16-mg dose level, and two DLTs (hypertension and fatigue) occurred at the 20-mg dose level.

“[At 20 mg,] patients were unable to take more than 75% of the study drug during the first cycle, and that was considered a DLT,” Dr. Backes said. “So our recommended phase 2 dose was lenvatinib 16 mg daily and paclitaxel 80 mg.”

Safety

“Toxicities were fairly common,” Dr. Backes noted. “The majority of these were cytopenias, but we also saw some GI toxicity – mucositis, diarrhea, nausea – and the VEGF inhibitor–related toxicities that we’re familiar with – hypertension, proteinuria, epistaxis. Fortunately, the majority of toxicities were grade 1 to 2.”

The most common AEs of any grade were leukopenia (58%), anemia (50%), mucositis (46%), diarrhea (46%), lymphopenia (42%), anorexia (42%), hypertension (42%), fatigue (42%), nausea (35%), proteinuria (27%), epistaxis (27%), and hoarseness (27%).

Grade 3 or higher AEs included hypertension (19%), neutropenia (15%), leukopenia (12%), anemia (12%), lymphopenia (8%), fatigue (8%), diarrhea (8%), mucositis (4%), vomiting (4%), hematuria (4%), rash (4%), and thrombocytopenia (4%).

“There was one patient [4%] who had a bowel perforation – small bowel perforation – at the site of previous stenosis after multiple prior bowel surgeries,” Dr. Backes noted.

Efficacy

In the 23 evaluable patients, the objective response rate was 65%, and the clinical benefit rate was 96%. One patient had a complete response, 14 had partial responses, 7 had stable disease, and 1 progressed.

The median duration of response was 10.9 months, and the median progression-free survival was 14.0 months.

The objective response rate was 71% in patients with ovarian cancer and 50% in patients with endometrial cancer. The median progression-free survival in these groups was 14.0 months and 12.8 months, respectively.

Dr. Backes said these results suggest lenvatinib plus paclitaxel is safe and active in recurrent ovarian and endometrial cancer, but these findings must be confirmed in a larger study.

This was an investigator-initiated study supported by Eisai. Dr. Backes disclosed relationships with Eisai, ImmunoGen, Clovis Oncology, Tesaro, Merck, and Agenus.

[email protected]

SOURCE: Backes FJ et al. SGO 2019, Abstract LBA5.

HONOLULU – Racial disparities in phase 1 gynecologic oncology clinical trial enrollment is nothing new, but the gap between African American and Caucasian enrollment widened in recent years, according to a review of studies conducted since 1985.

The literature review identified 357 relevant phase 1 studies involving 9,492 patients published between 1985 and 2018. However, only 83 of the studies (23%) included a racial breakdown; of the 2,483 patients in those 83 trials, 79% were Caucasian, 5% were African American, and 16% were of “other” race, Elias Awad reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Ovarian cancer was the most common tumor type studied, but among studies listing a racial breakdown, endometrial cancer studies had the highest enrollment of African American patients at 12%, said Mr. Awad, a 4th-year medical student at the University of South Alabama, Mobile. The remaining studies all had less than 10% participation of black patients.

“Also of note is that other races exceeded black patients in 55% of trials across all tumor types,” he said. “Despite the focus on increasing diversity in clinical trials over the years, the percentage of black patients has declined 1.8-fold from 11% in 1995-1999 to 6% in 2015-2018.”

Based on Centers for Disease Control and Prevention age-adjusted incidence for race, expected and observed ratios of racial participation were calculated – and were found to be less than expected for each tumor site, Mr. Awad said.

For example, the enrollment ratio in ovarian cancer studies was 0.04:1 for black and white patients, respectively, while the ratios for endometrial and cervical cancer were 0.004:1 and 0.025:1, respectively.

These ratios represent a 1,750% lower than expected enrollment of black patients in ovarian cancer trials, 2,080% lower than expected enrollment for endometrial cancer trials, and 5,300% lower than expected enrollment for cervical cancer, he said.

This lack of minority participation in early-phase clinical trials likely contributes to cancer health disparities, Mr. Awad added, explaining that the underrepresentation of minorities in trials results in agents that work in majority populations.

“Thus, it is paramount to have therapeutic agents specifically effective in minority populations,” he said. “Considering that phase 1 trials are the entry point for therapeutic success, these results further compound the lack of adequate clinical trials for our black patients who continue to suffer the consequences of these inequities.

“Accordingly, it is time to enact strategies to enhance equity in the enrollment of black patients on clinical trials in order to assist in eliminating racial disparities in gynecologic malignancies,” he concluded.

Mr. Awad reported having no financial disclosures.

[email protected]

SOURCE: Awad E et al. SGO 2019, Abstract 22.

HONOLULU – Racial disparities in phase 1 gynecologic oncology clinical trial enrollment is nothing new, but the gap between African American and Caucasian enrollment widened in recent years, according to a review of studies conducted since 1985.

The literature review identified 357 relevant phase 1 studies involving 9,492 patients published between 1985 and 2018. However, only 83 of the studies (23%) included a racial breakdown; of the 2,483 patients in those 83 trials, 79% were Caucasian, 5% were African American, and 16% were of “other” race, Elias Awad reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Ovarian cancer was the most common tumor type studied, but among studies listing a racial breakdown, endometrial cancer studies had the highest enrollment of African American patients at 12%, said Mr. Awad, a 4th-year medical student at the University of South Alabama, Mobile. The remaining studies all had less than 10% participation of black patients.

“Also of note is that other races exceeded black patients in 55% of trials across all tumor types,” he said. “Despite the focus on increasing diversity in clinical trials over the years, the percentage of black patients has declined 1.8-fold from 11% in 1995-1999 to 6% in 2015-2018.”

Based on Centers for Disease Control and Prevention age-adjusted incidence for race, expected and observed ratios of racial participation were calculated – and were found to be less than expected for each tumor site, Mr. Awad said.

For example, the enrollment ratio in ovarian cancer studies was 0.04:1 for black and white patients, respectively, while the ratios for endometrial and cervical cancer were 0.004:1 and 0.025:1, respectively.

These ratios represent a 1,750% lower than expected enrollment of black patients in ovarian cancer trials, 2,080% lower than expected enrollment for endometrial cancer trials, and 5,300% lower than expected enrollment for cervical cancer, he said.

This lack of minority participation in early-phase clinical trials likely contributes to cancer health disparities, Mr. Awad added, explaining that the underrepresentation of minorities in trials results in agents that work in majority populations.

“Thus, it is paramount to have therapeutic agents specifically effective in minority populations,” he said. “Considering that phase 1 trials are the entry point for therapeutic success, these results further compound the lack of adequate clinical trials for our black patients who continue to suffer the consequences of these inequities.

“Accordingly, it is time to enact strategies to enhance equity in the enrollment of black patients on clinical trials in order to assist in eliminating racial disparities in gynecologic malignancies,” he concluded.

Mr. Awad reported having no financial disclosures.

[email protected]

SOURCE: Awad E et al. SGO 2019, Abstract 22.

HONOLULU – Racial disparities in phase 1 gynecologic oncology clinical trial enrollment is nothing new, but the gap between African American and Caucasian enrollment widened in recent years, according to a review of studies conducted since 1985.

The literature review identified 357 relevant phase 1 studies involving 9,492 patients published between 1985 and 2018. However, only 83 of the studies (23%) included a racial breakdown; of the 2,483 patients in those 83 trials, 79% were Caucasian, 5% were African American, and 16% were of “other” race, Elias Awad reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Ovarian cancer was the most common tumor type studied, but among studies listing a racial breakdown, endometrial cancer studies had the highest enrollment of African American patients at 12%, said Mr. Awad, a 4th-year medical student at the University of South Alabama, Mobile. The remaining studies all had less than 10% participation of black patients.

“Also of note is that other races exceeded black patients in 55% of trials across all tumor types,” he said. “Despite the focus on increasing diversity in clinical trials over the years, the percentage of black patients has declined 1.8-fold from 11% in 1995-1999 to 6% in 2015-2018.”

Based on Centers for Disease Control and Prevention age-adjusted incidence for race, expected and observed ratios of racial participation were calculated – and were found to be less than expected for each tumor site, Mr. Awad said.

For example, the enrollment ratio in ovarian cancer studies was 0.04:1 for black and white patients, respectively, while the ratios for endometrial and cervical cancer were 0.004:1 and 0.025:1, respectively.

These ratios represent a 1,750% lower than expected enrollment of black patients in ovarian cancer trials, 2,080% lower than expected enrollment for endometrial cancer trials, and 5,300% lower than expected enrollment for cervical cancer, he said.

This lack of minority participation in early-phase clinical trials likely contributes to cancer health disparities, Mr. Awad added, explaining that the underrepresentation of minorities in trials results in agents that work in majority populations.

“Thus, it is paramount to have therapeutic agents specifically effective in minority populations,” he said. “Considering that phase 1 trials are the entry point for therapeutic success, these results further compound the lack of adequate clinical trials for our black patients who continue to suffer the consequences of these inequities.

“Accordingly, it is time to enact strategies to enhance equity in the enrollment of black patients on clinical trials in order to assist in eliminating racial disparities in gynecologic malignancies,” he concluded.

Mr. Awad reported having no financial disclosures.

[email protected]

SOURCE: Awad E et al. SGO 2019, Abstract 22.