Niraparib (PARP inhibitor) + dostarlimab (PD-1) maintenance cuts PFS risk ~40% in advanced/recurrent endometrial cancer—at major toxicity cost, no OS gain

Niraparib is an oral PARP inhibitor added to dostarlimab (anti–PD-1) maintenance after induction dostarlimab + carboplatin/paclitaxel in Part 2 of the Phase 3 ENGOT-EN6-NSGO/GOG-3031/RUBY trial (NCT03981796). In primary advanced or recurrent endometrial cancer (n=291; 2:1 randomization), niraparib+dostarlimab significantly improved PFS vs placebo maintenance (overall HR 0.60, p<.001; pMMR/MSS HR 0.63, p=.006) at ~22 months’ follow-up, but showed no OS benefit at 36.2 months (OS HR 1.2). Toxicity meaningfully worsened vs control: Grade ≥3 treatment-related AEs 70.7% vs 37.5%, serious treatment-related AEs 24.6% vs 9.4%, and discontinuations due to AEs 38.7% vs 11.5%—a harder-to-justify profile given that the contemporary frontline SOC already includes chemo + PD-1 (e.g., RUBY Part 1 dostarlimab+CP improved OS vs CP; HR ~0.69 in the overall population).