Comment on “Pembrolizumab Plus Weekly Paclitaxel in Platinum-resistant Recurrent Ovarian Cancer (ENGOT-Ov65/KEYNOTE-B96): A Multicentre, Randomized, Double-blind, Phase 3 Study”

Epithelial ovarian cancer has a high mortality rate and a high rate of recurrence, which is often associated with resistance to platinum chemotherapy. This resistance contributes to a poor prognosis for these patients. Studies show minimal benefit of non-platinum chemotherapy on progression-free survival and no benefit to overall survival. Preliminary trials have shown that a weekly administration of paclitaxel at a lower dose combined with pembrolizumab and/or other agents may be more effective in platinum-resistant recurrent ovarian cancer. The current study (ENGOT-ov65/KEYNOTE-B96) is a phase 3 study designed to assess if adding pembrolizumab to weekly paclitaxel with or without bevacizumab improves progression-free or overall survival compared with weekly paclitaxel with or without bevacizumab.

This study is a randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted in 187 sites and 25 countries. Inclusion criteria were age 18 and above, histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, including serous, low-grade serous, clear cell, carcinosarcoma, and endometrioid histology. Patients were treated with 1 or 2 previous lines of systemic therapy for ovarian cancer, including at least one platinum-based therapy. The study was double-blinded for the administration of pembrolizumab; participants were randomized in a 1:1 ratio to receive weekly paclitaxel with or without pembrolizumab, and the decision whether to use bevacizumab was made by the investigator before randomization based on clinical factors. The primary outcome for this study was progression-free survival defined as time from randomization to first documented disease progression or death from any cause. The secondary outcome was overall survival, and other outcomes included patient-reported outcomes of quality of life and adverse events.

Final analysis included 638 patients who received at least one dose of the treatment regimen, with 320 in the pembrolizumab group and 318 in the placebo group. Baseline characteristics were similar between groups. Addition of pembrolizumab significantly improved progression-free survival compared with placebo both in the overall population [hazard ratio (HR): 0.70, 95% CI: 0.58-0.84, P < 0.001, α = 0.0023] and in PD-L1–expressing tumors (HR: 0.72, 95% CI: 0.58-0.89, P = 0.0014, α = 0.012). Overall survival was not significantly improved at the first interim analysis but was improved at the second for PD-L1–expressing tumors (HR: 0.76, 95% CI: 0.61-0.94, P = 0.0053, α = 0.0021) but not in the overall population. The progression-free survival improvement was also evident at the second interim analysis in both the PD-L1 population and the overall population. At the final analysis, overall survival showed significant improvement in the overall population (HR: 0.82, 95% CI: 0.69-0.97, P = 0.011, α = 0.024) as well as in the PD-L1 population, and the progression-free survivalresults remained.

Adverse events occurred in 319 patients in the pembrolizumab group and 316 patients in the placebo group, with grade 3 or higher adverse events occurring in 265 patients in the pembrolizumab group and 225 patients in the placebo group. Grade 3 or higher adverse events related to treatment occurred in 217 patients in the pembrolizumab group and 176 patients in the placebo group. The most common adverse events were anemia, peripheral neuropathy, alopecia, fatigue, and nausea. Adverse events led to discontinuation in 107 patients in the pembrolizumab group and 63 patients in the placebo group.

These results indicate that the addition of pembrolizumab to weekly paclitaxel with or without bevacizumab significantly improved progression-free survival and overall survival in patients with platinum-resistant ovarian cancer. The safety profile of the pembrolizumab and paclitaxel regimen is consistent with other regimens of its kind and with those of the individual agents used. Future research should further evaluate the role of bevacizumab in this regimen, as well as increase the statistical power and study the effectiveness of this regimen in populations who have received more treatments prior to this regimen.

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