Pembrolizumab Plus Weekly Paclitaxel Improves Survival in Platinum-Resistant Ovarian Cancer
Results from the phase 3 ENGOT-ov65/KEYNOTE-B96 trial reveal that pembrolizumab combined with weekly paclitaxel, with or without bevacizumab, significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone in patients with platinum-resistant recurrent ovarian cancer.
These findings, presented at the 2025 European Society for Medical Oncology (ESMO) Congress, support this combination an emerging immunotherapy-based option in a setting long characterized by limited treatment efficacy.
The international, randomized, double-blind study enrolled 643 patients with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who had received 1 to 2 prior systemic regimens, including ≥4 cycles of a platinum-based therapy, and whose disease recurred within 6 months of their last platinum dose. Patients were randomized 1:1 to receive pembrolizumab (400 mg IV every 6 weeks) or placebo, each combined with weekly paclitaxel (80 mg/m² on days 1, 8, and 15 of each 3-week cycle) with optional bevacizumab (10 mg/kg every 2 weeks). Patients were treated until disease progression or unacceptable toxicity.
The primary trial end point was investigator-assessed PFS and OS was a key secondary end point.
At the first interim analysis (median follow-up, 15.6 months), pembrolizumab significantly improved PFS across all populations. Median PFS was 8.3 months vs 7.2 months in patients with PD-L1 CPS ≥1 (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.58 to 0.89; P = .0014) and 8.3 vs 6.4 months in the overall population (HR, 0.70; 95% CI, 0.58 to 0.84; P <.0001).
At the second interim analysis (median follow-up, 26.6 months), OS was also significantly prolonged in the PD-L1 CPS ≥1 subgroup, reaching 18.2 months vs 14 months (HR, 0.76; 95% CI, 0.61 to 0.94; P = .0053). A favorable trend was observed in the overall population (17.7 vs 14 months; HR, 0.81; 95% CI, 0.68 to 0.97; P = .0114). These improvements were consistent across key clinical subgroups, regardless of bevacizumab use.
Safety findings were consistent with known profiles of pembrolizumab and paclitaxel. Grade ≥3 treatment-related adverse events occurred in 67.5% of patients receiving pembrolizumab vs 55.3% with placebo. No new safety signals emerged, and immune-related adverse events were manageable with standard protocols.
These findings support pembrolizumab plus weekly paclitaxel, with or without bevacizumab as a new standard therapeutic option for patients with platinum-resistant ovarian cancer, delivering meaningful improvements in PFS and OS with manageable toxicity. The trial marks a pivotal advance in integrating immunotherapy into recurrent ovarian cancer management.
Source:
Colombo N, Zsiros E, Sebastionelli A, et al. Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: Results from the randomized double-blind phase III ENGOT-ov65/KEYNOTE-B96 study. Presented at the 2025 ESMO Congress; October 17-21, 2025. Berlin, Germany. LBA3
