Pembrolizumab (PD-1) + chemo → maintenance pembrolizumab + olaparib (PARP) extends PFS in BRCA–wild-type ovarian cancer

Pembrolizumab is an anti–PD-1 antibody and olaparib is a PARP inhibitor; in KEYLYNK-001 (ENGOT-OV43/GOG-3036; NCT03740165), patients with newly diagnosed stage III–IV BRCA1/2 non-mutated epithelial ovarian/primary peritoneal/fallopian tube cancer received pembrolizumab + platinum-taxane chemotherapy followed by maintenance pembrolizumab + olaparib vs pembrolizumab + chemo → pembrolizumab maintenance vs placebo + chemo → placebo maintenance (ITT n=1367; bevacizumab allowed per investigator). At final analysis (median follow-up 49.6 months), pembrolizumab-olaparib improved PFS vs control in PD-L1 CPS≥10 (HR 0.66, 95% CI 0.53–0.83) and in ITT (HR 0.71, 0.61–0.84), while pembrolizumab alone was not significant in CPS≥10 (HR 0.95, p=0.33). Grade ≥3 TRAEs were higher with pembrolizumab-olaparib (66%) vs pembrolizumab (56%) vs control (51%), driven largely by cytopenias (eg, anemia 22% vs 13% vs 11%); treatment-related deaths occurred in 1% vs <1% vs 0%—a tolerability tradeoff vs current first-line maintenance options where benefit in BRCA–wild-type/HRD-negative disease can be modest (eg, PAOLA-1 HRD-negative/unknown: median PFS 16.9 vs 16.0 months; HR 0.92 with olaparib+bevacizumab).