Pembrolizumab Improves Survival in Platinum-Resistant Ovarian Cancer
The phase 3 ENGOT-ov65/KEYNOTE-B96 trial confirms the drug’s place in future therapies.
Treatment options for platinum-resistant ovarian cancer (PROC) remain limited, but recent research findings demonstrate benefits for an increasing range of therapies.
Today’s late-breaking abstract, “Patient-reported outcomes from the phase 3 ENGOT-ov65/KEYNOTE-B96 trial of pembrolizumab versus placebo plus paclitaxel, with or without bevacizumab, in platinum-resistant ovarian cancer,” highlighted the first phase 3 trial to demonstrate both progression-free and overall survival benefits with an immune checkpoint inhibitor-based regimen in PROC.
“This represents a meaningful step forward in a population where progress has historically been limited,” said presenter Emese Zsiros, MD, PhD, FACOG, chair of the Department of Gynecologic Oncology at Roswell Park Comprehensive Cancer Center in Buffalo, New York.
ENGOT-ov65/KEYNOTE-B96 is a randomized, double-blind, placebo-controlled phase 3 trial in which 643 participants were given either 400 mg of pembrolizumab intravenously or a placebo every six weeks. Both groups received weekly paclitaxel, with or without bevacizumab administered at the investigator’s discretion.
Eligible participants were 18 years of age and older with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. They also must have received one to two prior lines of systemic therapy, including at least one prior platinum-based regimen, and had platinum-resistant ovarian cancer. In the study, PROC was defined as radiographic progression within six months after the last platinum dose.
The study demonstrated improvements in progression-free and overall survival with pembrolizumab plus weekly paclitaxel compared with placebo plus weekly paclitaxel. In addition, pembrolizumab plus weekly paclitaxel, with or without bevacizumab, was associated with maintenance of health-related quality of life, and patient-reported symptom burden was similar between the treatment and control groups.
Dr. Zsiros said the results point toward a future with increased survival rates for patients with PROC.
“These results build on a growing body of recent phase 3 trials showing survival improvements in platinum-resistant ovarian disease and suggest that the choice and schedule of chemotherapy backbone may be critical to optimizing immunotherapy activity,” she said.
One of the most important aspects of the study related to that chemotherapy backbone, according to Dr. Zsiros, is that immunotherapy was combined with weekly paclitaxel, which is known to have both cytotoxic and immunomodulatory effects.
“Weekly taxane schedules can influence the tumor microenvironment in ways that may enhance immune activation, for example, by promoting antigen release and modulating immune cell populations within the tumor,” she said.
Weekly paclitaxel has long been recognized as one of the more active chemotherapy options for platinum-resistant ovarian cancer. Dr. Zsiros said the findings from this trial suggest that pairing an immune checkpoint blockade with an effective immunologically favorable chemotherapy schedule may be important for maximizing benefit.
“This highlights that the choice and schedule of the chemotherapy partner may be an important determinant of how well immunotherapy performs in ovarian cancer,” she said.
As for the next steps, the regimen outlined in the trial recently received approval from the U.S. Food and Drug Administration based on the outcome of the trial. In addition, the Committee for Medicinal Products for Human Use — the European Medicines Agency’s (EMA) medication review body — has issued a favorable opinion, which puts the treatment one step closer to adoption by the EMA.
“These developments suggest that the regimen is moving rapidly into clinical practice and may become an important new treatment option for patients with platinum-resistant ovarian cancer,” said Dr. Zsiros.
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