Pembrolizumab Plus Weekly Paclitaxel in Platinum-Resistant Recurrent Ovarian Cancer - Article Summary

Summary Author: Ashley Lin

Background:

Epithelial ovarian cancer is the most prevalent type of ovarian cancer and is the leading cause of death among gynecologic malignancies. Platinum-resistant ovarian cancer is characterized by disease recurrence or progression within six months of completing platinum-based chemotherapy, carrying a poor prognosis. Pembrolizumab, an immune checkpoint inhibitor, binds to the PD-1 receptor on T-cells, blocking its interaction with PD-L1 and PD-L2. This action restores T-cell-mediated antitumor immune responses. The KEYNOTE-B96 study investigated whether adding pembrolizumab to a dose-dense paclitaxel regimen could improve outcomes in platinum-resistant recurrent ovarian cancer.

Study Design:

This multicenter, double-blind, phase 3 randomized controlled trial was conducted across 187 sites in 25 countries. 643 participants with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who had previously received one to two lines of systemic therapy were enrolled. Participants were randomized 1:1 to receive either intravenous (IV) pembrolizumab every six weeks plus weekly IV paclitaxel (n = 322) or IV placebo every six weeks plus weekly IV paclitaxel (n = 321). Based on the investigators' clinical judgment, participants could also receive IV bevacizumab every two weeks. Randomization was stratified by planned bevacizumab use, region of study enrollment, and tumor PD-L1 status. The primary endpoint was progression-free survival (PFS), and the main secondary endpoint was overall survival (OS).

Findings:

First interim analysis (9 months after enrollment end): Pembrolizumab plus paclitaxel improved PFS compared to placebo plus paclitaxel in the overall population (median 8.3 months vs. 6.4 months; hazard ratio [HR] 0.70; p < 0.0001).

Second interim analysis (20 months after enrollment end): Pembrolizumab plus paclitaxel improved OS compared to placebo plus paclitaxel among participants whose tumors demonstrated higher PD-L1 expression (median 18.2 months vs. 14.0 months; HR 0.76; p = 0.0053).

Final analysis (26 months after enrollment end): Pembrolizumab plus paclitaxel improved OS compared to placebo plus paclitaxel in the overall population (median 17.7 months vs. 14.0 months; HR 0.82; p = 0.011).

A greater percentage of participants in the pembrolizumab plus paclitaxel group (68%) experienced Grade 3 or higher treatment-related adverse events compared to the placebo plus paclitaxel group (55%).

Limitations:

Study eligibility was restricted to participants who had received one or two previous systemic therapies, which limits the generalizability of the findings to patients with a greater number of prior treatments. The investigator-discretionary use of bevacizumab may correlate with certain patient- or disease-related characteristics, potentially confounding the results.

Conclusions:

This study is the first to demonstrate an increase in overall survival with an immune checkpoint inhibitor regimen in platinum-resistant ovarian cancer. The favorable activity observed with weekly paclitaxel may be related in part to its proposed immunomodulatory effects compared with the conventional every-three-week dosing schedule. Based on these findings, the Food and Drug Administration approved the combination of pembrolizumab and paclitaxel in February 2026 for tumors with positive PD-L1 expression.

Main Takeaway

Pembrolizumab plus weekly paclitaxel, with or without bevacizumab, significantly improved progression-free survival and overall survival for patients who had previously received one or two systemic treatment regimens.

References:

Colombo N, Zsiros E, Parma G, et al. Pembrolizumab plus weekly paclitaxel in platinum-resistant recurrent ovarian cancer (ENGOT-ov65/KEYNOTE-B96): a multicentre, randomised, double-blind, phase 3 study. The Lancet. 2026;407(10538):1525-1537. doi:10.1016/S0140-6736(26)00602-1

Research C for DE and. FDA approves pembrolizumab with paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. FDA. Published online February 10, 2026. Accessed June 2, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-paclitaxel-platinum-resistant-epithelial-ovarian-fallopian-tube-or