Phase 3 trial reports progression-free and overall survival benefit with pembrolizumab plus weekly paclitaxel in platinum-resistant recurrent ovarian cancer

Evidence before this study

We searched PubMed, major conference proceedings, and up to Jan 31, 2026, for phase 2–3 studies evaluating immune checkpoint inhibitors for platinum-resistant recurrent ovarian cancer using the keywords: “ovarian cancer”, “platinum-resistant”, “recurrent ovarian cancer”, “immune checkpoint inhibitor”, “pembrolizumab”, “paclitaxel”, “metronomic paclitaxel”, “phase 2”, and “phase 3”. In the KEYNOTE-028 and KEYNOTE-100 studies, pembrolizumab monotherapy showed modest activity in recurrent ovarian cancer, with objective response rates of 8–12% and greater benefit in PD-L1-expressing tumours. Several investigator-initiated studies explored combination immunotherapy strategies in this setting. A phase 2 study () of weekly paclitaxel plus pembrolizumab suggested encouraging efficacy compared with historical weekly paclitaxel. In another phase 2 study (), pembrolizumab combined with bevacizumab and oral metronomic cyclophosphamide produced an objective response rate of 43% and a median progression-free survival of 7·6 months in the platinum-resistant cohort, supporting the rationale for combining immunotherapy with immune-modulating or metronomic chemotherapy.

Two randomised phase 3 trials, evaluating atezolizumab (AGO-OVAR 2.29/ENGOT-ov34, ) or avelumab (JAVELIN Ovarian 200, ) added to single-agent chemotherapy (pegylated liposomal doxorubicin or weekly paclitaxel), did not show statistically significant improvements in progression-free survival or overall survival in unselected platinum-resistant recurrent ovarian cancer populations. However, exploratory analyses suggested higher activity when immune checkpoint inhibitors were combined with weekly paclitaxel compared with other chemotherapy backbones. This observation is consistent with preclinical evidence that metronomic or low-dose taxanes can enhance antigen presentation, reduce immunosuppressive cell populations, and enhance the activity of immune checkpoint blockade.

Although between-trial differences preclude direct comparisons, several recent studies in platinum-resistant ovarian cancer, MIRASOL (mirvetuximab soravtansine), SCORES (suvemcitug plus chemotherapy), and ROSELLA (relacorilant plus nab-paclitaxel), have shown significant improvements in progression-free survival and overall survival after decades of largely negative results in this setting. To our knowledge, no previous randomised phase 3 study had demonstrated an overall survival benefit with an immune checkpoint inhibitor–based regimen in ovarian cancer and the potential benefit of combining pembrolizumab and weekly paclitaxel had not been validated in a definitive trial.

Added value of this study

The randomised, placebo-controlled phase 3 ENGOT-ov65/KEYNOTE-B96 study showed that adding pembrolizumab to weekly paclitaxel, with or without bevacizumab, significantly prolongs progression-free survival and overall survival in platinum-resistant recurrent ovarian cancer in both the PD-L1 combined positive score 1 or higher and the overall populations, representing the first demonstration of an overall survival benefit with an immune checkpoint inhibitor regimen in ovarian cancer. The magnitude and consistency of benefit across clinically relevant subgroups—including older patients, those previously treated with poly(ADP-ribose) polymerase inhibitors, and those with short platinum-free intervals—underscore the robustness of these findings. Safety outcomes were consistent with the known profiles of pembrolizumab and weekly paclitaxel, with no new safety signals and manageable immune-mediated adverse events.

Implications of all the available evidence

Taken together with previous negative phase 3 trials of immune checkpoint inhibitors combined with non-metronomic chemotherapy in platinum-resistant recurrent ovarian cancer, the findings from ENGOT-ov65/KEYNOTE-B96 indicate that the choice and schedule of chemotherapy are critical determinants of immunotherapy effectiveness. Weekly (metronomic) paclitaxel appears to potentiate checkpoint blockade, consistent with translational data suggesting enhanced antigen presentation, reduced immunosuppressive cell populations, and a more immunogenic tumour microenvironment with metronomic dosing. These results establish pembrolizumab plus weekly paclitaxel, with or without bevacizumab, as an effective treatment option for platinum-resistant recurrent ovarian cancer, provide the first randomised evidence of an overall survival benefit with immunotherapy in ovarian cancer, and support this regimen as a new standard of care.

Source: The Lancet