FDA Approves Pembrolizumab With Chemotherapy for Advanced, Recurrent Endometrial Cancer

This week, the US Food and Drug Administration (FDA) approved pembrolizumab with carboplatin and paclitaxel for adult patients with primary advanced or recurrent endometrial carcinoma.

The efficacy of this treatment combination was assessed in KEYNOTE-868/NRG-GY018, a multicenter, randomized, double-blind, placebo-controlled trial comprising 810 patients with advanced or recurrent endometrial carcinoma. The trial, consisting of 2 separate cohorts based on mismatch repair (MMR) status, included 222 patients in the MMR deficient (dMMR) cohort and 588 patients in the MMR proficient (pMMR) cohort. Subsequently, study subjects were randomized (1:1) to the following treatment arms:

• Pembrolizumab 200 mg every 3 weeks, paclitaxel 175 mg/m² and carboplatin AUC 5 mg/mL/min for 6 cycles, followed by pembrolizumab 400 mg every 6 weeks for up to 14 cycles
• Placebo every 3 weeks, paclitaxel 175 mg/m² and carboplatin AUC 5 mg/mL/min for 6 cycles, followed by placebo every 6 weeks for up to 14 cycles

The key efficacy end point was defined as progression-free survival (PFS).

According to the results, in the dMMR cohort, median PFS was not reached (NR; 95% CI, 30.7 to NR) in the pembrolizumab and chemotherapy arm and 6.5 months (95% CI, 6.4-8.7) in the placebo and chemotherapy arm (hazard ratio [HR], 0.30 [95% CI: 0.19-0.48]; P-value<.0001). However, in the pMMR cohort, median PFS was 11.1 months (95% CI, 8.7-13.5) in the pembrolizumab and chemotherapy arm and 8.5 months (95% CI, 7.2-8.8) in the placebo and chemotherapy arm (HR, 0.60 [95% CI: 0.46-0.78; P-value<.0001).