Background
Phase 3, open-label, randomized, active-comparator trial at 122 centres in 24 countries. N=299. First-line inoperable stage III/IV, persistent or recurrent dMMR endometrial cancer. Tests a chemotherapy-free PD-1 approach.
Results
Interventions and follow up: Arm A: pembrolizumab 400 mg IV q6w, up to 18 cycles (n=149)
Arm B: carboplatin AUC 5-6 + paclitaxel 175 mg/m2 q3w x6 (n=150)
Primary endpoints: PFS (BICR, RECIST 1.1) and OS
mFollow up: NR (interim analysis, cutoff Apr 24, 2026)
Results: PFS: median 38.2 mo (95% CI 17.9-NR) vs 8.4 mo (6.8-10.4); HR 0.57 (0.42-0.79); P=.0002
PFS rate 6 mo: 75% vs 76%
PFS rate 12 mo: 67% vs 40%
PFS rate 36 mo: 53% vs 30%
OS: medians NR; HR 0.77 (0.52-1.15); P=.10 (prespecified significance not met at interim)
Arm B: carboplatin AUC 5-6 + paclitaxel 175 mg/m2 q3w x6 (n=150)
Primary endpoints: PFS (BICR, RECIST 1.1) and OS
mFollow up: NR (interim analysis, cutoff Apr 24, 2026)
Results: PFS: median 38.2 mo (95% CI 17.9-NR) vs 8.4 mo (6.8-10.4); HR 0.57 (0.42-0.79); P=.0002
PFS rate 6 mo: 75% vs 76%
PFS rate 12 mo: 67% vs 40%
PFS rate 36 mo: 53% vs 30%
OS: medians NR; HR 0.77 (0.52-1.15); P=.10 (prespecified significance not met at interim)
Adverse events
Grade ≥3 TRAEs: 18% vs 51%
Alopecia: 2% vs 50%
Anemia: 5% vs 49%
Neutropenia: 3% vs 28%
Peripheral neuropathy: 0% vs 26%
Discontinuation (TRAE): 9% vs 15%
Treatment-related deaths: 2 vs 1
Alopecia: 2% vs 50%
Anemia: 5% vs 49%
Neutropenia: 3% vs 28%
Peripheral neuropathy: 0% vs 26%
Discontinuation (TRAE): 9% vs 15%
Treatment-related deaths: 2 vs 1
Conclusions
Pembrolizumab monotherapy significantly improved PFS versus carboplatin-paclitaxel in first-line dMMR endometrial cancer, with markedly less grade ≥3 toxicity. OS is immature and not yet significant.
Key Limitations
Interim analysis; OS not significant and medians not reached. Open-label design. Control arm was chemotherapy alone, which is no longer the standard in dMMR disease; pembrolizumab was not compared with PD-1 inhibitor plus chemotherapy (as acknowledged by the authors). Early PFS curves are similar (6-mo PFS 75% vs 76%), with separation emerging later.
Clinical Context
Current first-line standard for advanced/recurrent endometrial cancer is chemotherapy plus a PD-1/PD-L1 inhibitor (e.g., RUBY, NRG-GY018, DUO-E), with large benefit in dMMR. KEYNOTE-C93 supports a chemotherapy-free option for dMMR patients, but the lack of an immunotherapy-plus-chemotherapy comparator and immature OS limit immediate practice change. No regulatory action is cited here.
