Multinational phase 3 trial of pembrolizumab plus weekly paclitaxel in platinum-resistant ovarian cancer

The phase 3 ENGOT-ov65/KEYNOTE-B96 trial, at 187 centers in 25 countries, evaluated addition of pembrolizumab to weekly paclitaxel with or without bevacizumab in patients with platinum-resistant ovarian cancer (PROC) who had received one or two previous systemic regimens, with progression 6 months or less after the last platinum regimen. Patients were randomized 1:1 to pembrolizumab (n=322) or placebo (n=321) for up to 18 six-week cycles, both in combination with paclitaxel; bevacizumab every two weeks was permitted per investigator. The primary endpoint was investigator assessed progression-free survival (PFS). At the first interim analysis, pembrolizumab plus paclitaxel significantly improved PFS versus placebo plus paclitaxel in both the PD-L1 CPS 1 or higher (median 8.3 versus 7.2 months; HR 0.72; p=0.0014) and overall populations (median 8.3 months versus 6.4 months; HR 0.0.70; p<0.0001). At the second interim analysis, overall survival (OS) was significantly improved in the PD L1 CPS1 or higher population (median 18.2 months versus 14.0 months; HR 0.76; p=0.0053). At the final analysis, OS was significantly improved in the overall population (median 17.7 months versus 14.0 months; HR 0.82; p=0.011). Grade 3 or worse treatment-related adverse events occurred in 68% of patients in the pembrolizumab plus paclitaxel group and 55% of patients in the placebo plus paclitaxel group; treatment-related occurred in four and five patients, respectively. The authors conclude that pembolizumab plus paclitaxel, with or without bevacizumab, significantly improved PFS and OS in PROC patients who had received one or two previous systemic regimens.