FDA officials approved pembrolizumab (Keytruda, Merck) with carboplatin and paclitaxel, followed by single- agent pembrolizumab, for adult patients with primary advanced or recurrent endometrial carcinoma on June 17, 2024.
The efficacy of this treatment was evaluated in KEYNOTE-868/NRG-GY018 (NCT03914612), a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 810 patients with advanced or recurrent endometrial carcinoma. The trial included 2 separate cohorts based on mismatch repair (MMR) status: 222 patients in the mismatch repair deficient (dMMR) cohort, and 588 patients in the mismatch repair proficient (pMMR) cohort.
Patients were randomly assigned (1:1) to one of 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
Randomization was stratified according to MMR status, ECOG performance status (0 or 1 vs 2), and prior adjuvant chemotherapy. The major efficacy outcome measure was progression- free survival (PFS), assessed by the investigator according to RECIST 1.1. In the dMMR cohort, median PFS was not reached (NR) (95% CI: 30.7, NR) in the pembrolizumab and chemotherapy arm and was 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<.001)
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) for those receiving placebo and chemotherapy (HR 0.60 [95% CI: 0.46, 0.78; P<.001).Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported with the exception of a higher incidence of rash.
Reference