In the Journals

Nivolumab-bevacizumab combination safe, active in relapsed ovarian cancer

A combination of nivolumab and bevacizumab appeared safe and induced responses among women with relapsed ovarian cancer, according to results of a single-arm, phase 2 trial published in JAMA Oncology.

Researchers observed higher rates of response among women with platinum-sensitive disease.

“Studies performed in archival epithelial ovarian cancer specimens support the notion that the immune system is actively involved in ovarian cancer control,” Joyce F. Liu, MD, MPH, director of clinical research in the division of gynecologic oncology at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School, and colleagues wrote. “Similarly, increased PD-L1 or PD-L2 expression has also been reported to correlate with poorer OS in ovarian cancer, supporting the hypothesis that signaling via the PD-1/PD-L1 immune checkpoint is a mechanism of immune evasion in these tumors.”

Although PD-1/PD-L1 inhibitors have shown limited activity as single agents in ovarian cancer, Lin and colleagues hypothesized that the combination of antiangiogenic therapy with bevacizumab (Avastin, Genentech) and PD-1/PD-L1 inhibition with nivolumab would induce synergistic activity by modulating the tumor microenvironment.

Their study included 38 women (mean age, 63 years) with platinum-resistant (n = 18) or platinum-sensitive (n = 20) relapsed epithelial ovarian cancer. All of the women had experienced disease recurrence within 12 months of their last platinum-based therapy and had as many as three lines of prior therapy.

Researchers assigned the women to receive 240 mg IV nivolumab (Opdivo, Bristol-Myers Squibb) and 10 mg/kg IV bevacizumab once every 2 weeks.

Objective response rate served as the study’s primary endpoint. ORR by platinum sensitivity, PFS, safety, and analysis of the association between tumor PD-L1 with response to therapy served as secondary endpoints.

Results showed 11 confirmed responses, for an ORR of 28.9% (95% CI, 15.4-45.9).

Women with platinum-sensitive disease demonstrated a higher ORR (40%; 95% CI, 19.1-64) than women with platinum-resistant disease (16.7%; 95% CI, 3.6-41.4).

Median duration of response was 6 months, and median PFS was 8.1 months (95% CI, 6.3-14.)

Women with platinum-resistant disease had a longer median duration of response than women with platinum-sensitive disease (12.3 months vs. 5.6 months) but shorter median PFS (5.3 months vs. 9.4 months).

Thirty-four women (89.5%) experienced one or more treatment-related adverse events, including nine with grade 3 or higher adverse events. Common adverse events included fatigue (n = 18), headache (n = 11), myalgia (n = 11), serum amylase level increase (n = 11), aspartate aminotransferase level increase (n = 10) and hypertension (n = 10).

PD-L1 testing performed on 36 histologic samples showed 22 women had a PD-L1 tumor percentage lower than 1, whereas 14 had a percentage of 1 or more. Researchers observed 10 responses among women with a PD-L1 tumor percentage below 1, and two among women with a percentage of 1 or more.

The small sample size and lack of randomization, served as the study’s primary limitations.

“The findings suggest that combination therapy with nivolumab and bevacizumab is safe and tolerable in women with relapsed ovarian cancer and may provide evidence of clinical activity,” Liu and colleagues wrote. “Given the limited activity of single-agent PD-1/PD-L1- directed therapy in ovarian cancer, combination studies of immune checkpoint inhibitors with other agents are of growing interest in this disease.” – by John DeRosier

Disclosures: Liu reports research funding from AstraZeneca, Clovis Oncology, Genentech/Roche, Mersana Therapeutics and Tesaro, and a consultant role with Merck. Please see the study for all other authors’ relevant financial disclosures.

A combination of nivolumab and bevacizumab appeared safe and induced responses among women with relapsed ovarian cancer, according to results of a single-arm, phase 2 trial published in JAMA Oncology.

Researchers observed higher rates of response among women with platinum-sensitive disease.

“Studies performed in archival epithelial ovarian cancer specimens support the notion that the immune system is actively involved in ovarian cancer control,” Joyce F. Liu, MD, MPH, director of clinical research in the division of gynecologic oncology at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School, and colleagues wrote. “Similarly, increased PD-L1 or PD-L2 expression has also been reported to correlate with poorer OS in ovarian cancer, supporting the hypothesis that signaling via the PD-1/PD-L1 immune checkpoint is a mechanism of immune evasion in these tumors.”

Although PD-1/PD-L1 inhibitors have shown limited activity as single agents in ovarian cancer, Lin and colleagues hypothesized that the combination of antiangiogenic therapy with bevacizumab (Avastin, Genentech) and PD-1/PD-L1 inhibition with nivolumab would induce synergistic activity by modulating the tumor microenvironment.

Their study included 38 women (mean age, 63 years) with platinum-resistant (n = 18) or platinum-sensitive (n = 20) relapsed epithelial ovarian cancer. All of the women had experienced disease recurrence within 12 months of their last platinum-based therapy and had as many as three lines of prior therapy.

Researchers assigned the women to receive 240 mg IV nivolumab (Opdivo, Bristol-Myers Squibb) and 10 mg/kg IV bevacizumab once every 2 weeks.

Objective response rate served as the study’s primary endpoint. ORR by platinum sensitivity, PFS, safety, and analysis of the association between tumor PD-L1 with response to therapy served as secondary endpoints.

Results showed 11 confirmed responses, for an ORR of 28.9% (95% CI, 15.4-45.9).

Women with platinum-sensitive disease demonstrated a higher ORR (40%; 95% CI, 19.1-64) than women with platinum-resistant disease (16.7%; 95% CI, 3.6-41.4).

Median duration of response was 6 months, and median PFS was 8.1 months (95% CI, 6.3-14.)

Women with platinum-resistant disease had a longer median duration of response than women with platinum-sensitive disease (12.3 months vs. 5.6 months) but shorter median PFS (5.3 months vs. 9.4 months).

Thirty-four women (89.5%) experienced one or more treatment-related adverse events, including nine with grade 3 or higher adverse events. Common adverse events included fatigue (n = 18), headache (n = 11), myalgia (n = 11), serum amylase level increase (n = 11), aspartate aminotransferase level increase (n = 10) and hypertension (n = 10).

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PD-L1 testing performed on 36 histologic samples showed 22 women had a PD-L1 tumor percentage lower than 1, whereas 14 had a percentage of 1 or more. Researchers observed 10 responses among women with a PD-L1 tumor percentage below 1, and two among women with a percentage of 1 or more.

The small sample size and lack of randomization, served as the study’s primary limitations.

“The findings suggest that combination therapy with nivolumab and bevacizumab is safe and tolerable in women with relapsed ovarian cancer and may provide evidence of clinical activity,” Liu and colleagues wrote. “Given the limited activity of single-agent PD-1/PD-L1- directed therapy in ovarian cancer, combination studies of immune checkpoint inhibitors with other agents are of growing interest in this disease.” – by John DeRosier

Disclosures: Liu reports research funding from AstraZeneca, Clovis Oncology, Genentech/Roche, Mersana Therapeutics and Tesaro, and a consultant role with Merck. Please see the study for all other authors’ relevant financial disclosures.

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