Pembrolizumab (PD-1) + carboplatin/paclitaxel sustains 48-mo OS gains in dMMR endometrial cancer

Pembrolizumab is an anti–PD-1 checkpoint inhibitor added to carboplatin/paclitaxel (CP) induction (6 cycles Q3W) followed by pembrolizumab maintenance (Q6W up to 24 months) in the Phase 3, randomized NRG-GY018/KEYNOTE-868 trial (NCT03914612) in primary advanced or recurrent endometrial cancer (n=810), analyzed separately in dMMR vs pMMR cohorts with an OS cutoff of December 23, 2025. In dMMR disease (median follow-up 44.6 mo), 48-month OS was 80% with pembrolizumab+CP vs 60% with placebo+CP (HR 0.53, 95% CI 0.32–0.89), despite substantial post-study ICI crossover (≥55%, n=62 in the placebo arm); in pMMR (median follow-up 40.1 mo; information fraction 78%), median OS was 46.9 vs 35.1 months (HR 0.84, 95% CI 0.66–1.06) despite ≥57% (n=167) of placebo patients receiving post-study ICI (most commonly lenvatinib+pembrolizumab; median ICI duration 6.2 mo in both arms). Clinically, this supports using PD-1 + CP up front (now FDA-approved in this setting) rather than “saving” immunotherapy for later lines—especially since the common salvage option in pMMR (lenvatinib+pembrolizumab after prior platinum) historically delivers mOS ~18.0 vs 12.2 months vs chemo in KEYNOTE-775, with meaningful toxicity tradeoffs that many patients struggle to tolerate long-term.