TBD Meeting (2910-19)

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 – 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.

HONOLULU – The improved progression-free survival and reduced risk of disease progression seen with maintenance rucaparib versus placebo in women with recurrent ovarian cancer in the pivotal ARIEL3 study occurred across age subgroups, according to a post hoc exploratory analysis of data from the phase 3 study.

In general, the safety profile of the first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor was consistent across age groups, as well, but rates of dose modifications and treatment discontinuations varied slightly by age subgroup in the rucaparib (Rubraca)and placebo arms, Jonathan A. Ledermann, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

No clear trend emerged with respect to those differences, said Dr. Ledermann, a professor of medical oncology at University College of London Cancer Institute and UCL Hospitals.

Initial results from the randomized, placebo-controlled study were published in 2017 and showed a significant progression-free survival (PFS) benefit with 600 mg of maintenance rucaparib vs. placebo (10.8 vs. 5.4 months, respectively, in the intention-to-treat population). For the current analysis, outcomes were assessed for the ITT population across three baseline age-based subgroups: those under age 65 years, those aged 65-74 years, and those 75 years or older.

Investigator-assessed PFS – the primary endpoint of ARIEL3 – for the rucaparib vs. placebo groups was 11.1 vs. 5.4 months among 237 and 117 patients under age 65 years in the groups, respectively (hazard ratio, 0.33); 8.3 vs. 5.3 for 113 and 64 patients aged 65-74 years, respectively (HR, 0.43); and 9.2 and 5.5 months in 25 and 8 patients aged 75 and older (HR, 0.47), he said.

“The hazard ratios are comparable across all three age cohorts,” Dr. Ledermann said.

Treatment-emergent adverse events (TEAEs) of any grade occurring in at least 35% of patients included nausea, asthenia, vomiting, dysgeusia, constipation, anemia, ALT/AST increase, diarrhea, abdominal pain, thrombocytopenia, and pruritus.

The rates of these events were similar across age groups, although slight, nonsignificant numerical increases in grade 3 toxicities occurred with increasing age, he noted.

“If we look at dose interruption and dose reduction rates – again, broadly similar, [but with] a slight trend toward an increase in older age groups,” he said.

Dose modifications related to TEAEs, however, occurred in 65.5% of rucaparib and 9.4% of placebo patients aged under 65 years, compared with 82.3% and 12.5% of those aged 65-74, and 83.3% and 12.5% of those aged 75 or older, respectively. Discontinuations because of TEAEs occurred in 13.6% and 1.7% in those under age 65 years vs. 19.5% and 3.1% in those aged 65-74 years, and 20.8% and 0% of those aged 75 years or older in the groups, respectively.

Of note, the age subgroups and the treatment and placebo groups were well balanced except more of those under age 65 years had a deleterious germline or somatic BRCA mutation (96 and 49 in the rucaparib and placebo arms, respectively) than did patients aged 65-74 years (29 and 15, respectively), and patients aged 75 years and older (5 and 2, respectively).

ARIEL3 was funded by Clovis Oncology. Dr. Ledermann reported financial relationships (consulting, grant receipt, honorarial reimbursement, and/or speakers bureau fees) with AstraZeneca, Clovis Oncology, Pfizer, Seattle Genetics, Roche, and MSD/Merck.

[email protected]

SOURCE: Ledermann J et al. SGO 2019, Abstract 4.

HONOLULU – The improved progression-free survival and reduced risk of disease progression seen with maintenance rucaparib versus placebo in women with recurrent ovarian cancer in the pivotal ARIEL3 study occurred across age subgroups, according to a post hoc exploratory analysis of data from the phase 3 study.

In general, the safety profile of the first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor was consistent across age groups, as well, but rates of dose modifications and treatment discontinuations varied slightly by age subgroup in the rucaparib (Rubraca)and placebo arms, Jonathan A. Ledermann, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

No clear trend emerged with respect to those differences, said Dr. Ledermann, a professor of medical oncology at University College of London Cancer Institute and UCL Hospitals.

Initial results from the randomized, placebo-controlled study were published in 2017 and showed a significant progression-free survival (PFS) benefit with 600 mg of maintenance rucaparib vs. placebo (10.8 vs. 5.4 months, respectively, in the intention-to-treat population). For the current analysis, outcomes were assessed for the ITT population across three baseline age-based subgroups: those under age 65 years, those aged 65-74 years, and those 75 years or older.

Investigator-assessed PFS – the primary endpoint of ARIEL3 – for the rucaparib vs. placebo groups was 11.1 vs. 5.4 months among 237 and 117 patients under age 65 years in the groups, respectively (hazard ratio, 0.33); 8.3 vs. 5.3 for 113 and 64 patients aged 65-74 years, respectively (HR, 0.43); and 9.2 and 5.5 months in 25 and 8 patients aged 75 and older (HR, 0.47), he said.

“The hazard ratios are comparable across all three age cohorts,” Dr. Ledermann said.

Treatment-emergent adverse events (TEAEs) of any grade occurring in at least 35% of patients included nausea, asthenia, vomiting, dysgeusia, constipation, anemia, ALT/AST increase, diarrhea, abdominal pain, thrombocytopenia, and pruritus.

The rates of these events were similar across age groups, although slight, nonsignificant numerical increases in grade 3 toxicities occurred with increasing age, he noted.

“If we look at dose interruption and dose reduction rates – again, broadly similar, [but with] a slight trend toward an increase in older age groups,” he said.

Dose modifications related to TEAEs, however, occurred in 65.5% of rucaparib and 9.4% of placebo patients aged under 65 years, compared with 82.3% and 12.5% of those aged 65-74, and 83.3% and 12.5% of those aged 75 or older, respectively. Discontinuations because of TEAEs occurred in 13.6% and 1.7% in those under age 65 years vs. 19.5% and 3.1% in those aged 65-74 years, and 20.8% and 0% of those aged 75 years or older in the groups, respectively.

Of note, the age subgroups and the treatment and placebo groups were well balanced except more of those under age 65 years had a deleterious germline or somatic BRCA mutation (96 and 49 in the rucaparib and placebo arms, respectively) than did patients aged 65-74 years (29 and 15, respectively), and patients aged 75 years and older (5 and 2, respectively).

ARIEL3 was funded by Clovis Oncology. Dr. Ledermann reported financial relationships (consulting, grant receipt, honorarial reimbursement, and/or speakers bureau fees) with AstraZeneca, Clovis Oncology, Pfizer, Seattle Genetics, Roche, and MSD/Merck.

[email protected]

SOURCE: Ledermann J et al. SGO 2019, Abstract 4.

HONOLULU – The improved progression-free survival and reduced risk of disease progression seen with maintenance rucaparib versus placebo in women with recurrent ovarian cancer in the pivotal ARIEL3 study occurred across age subgroups, according to a post hoc exploratory analysis of data from the phase 3 study.

In general, the safety profile of the first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor was consistent across age groups, as well, but rates of dose modifications and treatment discontinuations varied slightly by age subgroup in the rucaparib (Rubraca)and placebo arms, Jonathan A. Ledermann, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

No clear trend emerged with respect to those differences, said Dr. Ledermann, a professor of medical oncology at University College of London Cancer Institute and UCL Hospitals.

Initial results from the randomized, placebo-controlled study were published in 2017 and showed a significant progression-free survival (PFS) benefit with 600 mg of maintenance rucaparib vs. placebo (10.8 vs. 5.4 months, respectively, in the intention-to-treat population). For the current analysis, outcomes were assessed for the ITT population across three baseline age-based subgroups: those under age 65 years, those aged 65-74 years, and those 75 years or older.

Investigator-assessed PFS – the primary endpoint of ARIEL3 – for the rucaparib vs. placebo groups was 11.1 vs. 5.4 months among 237 and 117 patients under age 65 years in the groups, respectively (hazard ratio, 0.33); 8.3 vs. 5.3 for 113 and 64 patients aged 65-74 years, respectively (HR, 0.43); and 9.2 and 5.5 months in 25 and 8 patients aged 75 and older (HR, 0.47), he said.

“The hazard ratios are comparable across all three age cohorts,” Dr. Ledermann said.

Treatment-emergent adverse events (TEAEs) of any grade occurring in at least 35% of patients included nausea, asthenia, vomiting, dysgeusia, constipation, anemia, ALT/AST increase, diarrhea, abdominal pain, thrombocytopenia, and pruritus.

The rates of these events were similar across age groups, although slight, nonsignificant numerical increases in grade 3 toxicities occurred with increasing age, he noted.

“If we look at dose interruption and dose reduction rates – again, broadly similar, [but with] a slight trend toward an increase in older age groups,” he said.

Dose modifications related to TEAEs, however, occurred in 65.5% of rucaparib and 9.4% of placebo patients aged under 65 years, compared with 82.3% and 12.5% of those aged 65-74, and 83.3% and 12.5% of those aged 75 or older, respectively. Discontinuations because of TEAEs occurred in 13.6% and 1.7% in those under age 65 years vs. 19.5% and 3.1% in those aged 65-74 years, and 20.8% and 0% of those aged 75 years or older in the groups, respectively.

Of note, the age subgroups and the treatment and placebo groups were well balanced except more of those under age 65 years had a deleterious germline or somatic BRCA mutation (96 and 49 in the rucaparib and placebo arms, respectively) than did patients aged 65-74 years (29 and 15, respectively), and patients aged 75 years and older (5 and 2, respectively).

ARIEL3 was funded by Clovis Oncology. Dr. Ledermann reported financial relationships (consulting, grant receipt, honorarial reimbursement, and/or speakers bureau fees) with AstraZeneca, Clovis Oncology, Pfizer, Seattle Genetics, Roche, and MSD/Merck.

[email protected]

SOURCE: Ledermann J et al. SGO 2019, Abstract 4.

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

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

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

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

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

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

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

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

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

Dr. D’Souza reported having no financial disclosures.

[email protected]

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

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

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

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

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

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

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

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

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

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

Dr. D’Souza reported having no financial disclosures.

[email protected]

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

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

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

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

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

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

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

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

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

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

Dr. D’Souza reported having no financial disclosures.

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Pierce had no disclosures.

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Pierce had no disclosures.

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Pierce had no disclosures.

[email protected]

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

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

Sharon Worcester/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Lu reported having no disclosures.

[email protected]

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

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

Sharon Worcester/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Lu reported having no disclosures.

[email protected]

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

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

Sharon Worcester/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Lu reported having no disclosures.

[email protected]

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

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

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

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

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

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

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

Results

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

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

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

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

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

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

Results

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

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

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

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

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

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

Results

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

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

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

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

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

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

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

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

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

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

[email protected]

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