Background
Phase 3, randomized, double-blind, placebo-controlled trial (ENGOT-OV43/GOG-3036/KEYLYNK-001; NCT03740165) at 224 centers in 22 countries. N=1367 (ITT) with newly diagnosed stage III-IV BRCA1/2 non-mutated epithelial ovarian, primary peritoneal, or fallopian tube cancer. Three arms; bevacizumab permitted at investigator discretion. Evaluates adding pembrolizumab ± olaparib maintenance to first-line platinum chemotherapy.
Results
Interventions and follow up: Arm A (pembrolizumab-olaparib, n=455): chemo + pembrolizumab → maintenance pembrolizumab + olaparib
Arm B (pembrolizumab, n=458): chemo + pembrolizumab → pembrolizumab + placebo
Arm C (control, n=454): chemo + placebo → placebo
Primary endpoint: PFS (tested first in PD-L1 CPS ≥10, then ITT)
mFollow up: 30.1 mo (first interim); 49.6 mo (final)
Results: PFS (pembro-olaparib vs control), CPS≥10: HR 0.63 (0.49-0.80, P<.0001)
PFS, ITT: HR 0.68 (0.58-0.81, P<.0001)
PFS at final analysis: CPS≥10 HR 0.66 (0.53-0.83); ITT HR 0.71 (0.61-0.84)
Pembrolizumab alone vs control (CPS≥10): HR 0.95 (0.77-1.19, P=.33) — not significant, no further ITT testing
OS: NR
Arm B (pembrolizumab, n=458): chemo + pembrolizumab → pembrolizumab + placebo
Arm C (control, n=454): chemo + placebo → placebo
Primary endpoint: PFS (tested first in PD-L1 CPS ≥10, then ITT)
mFollow up: 30.1 mo (first interim); 49.6 mo (final)
Results: PFS (pembro-olaparib vs control), CPS≥10: HR 0.63 (0.49-0.80, P<.0001)
PFS, ITT: HR 0.68 (0.58-0.81, P<.0001)
PFS at final analysis: CPS≥10 HR 0.66 (0.53-0.83); ITT HR 0.71 (0.61-0.84)
Pembrolizumab alone vs control (CPS≥10): HR 0.95 (0.77-1.19, P=.33) — not significant, no further ITT testing
OS: NR
Adverse events
Grade ≥3 TRAE: 66% vs 56% vs 51% (A/B/C)
Most common: neutropenia, anemia, decreased neutrophil count
Serious TRAE: 24% vs 21% vs 9%
TRAE deaths: 4 (pembro-olaparib), 1 (pembro)
Most common: neutropenia, anemia, decreased neutrophil count
Serious TRAE: 24% vs 21% vs 9%
TRAE deaths: 4 (pembro-olaparib), 1 (pembro)
Conclusions
Adding pembrolizumab plus olaparib maintenance significantly improved PFS versus chemotherapy in BRCA non-mutated advanced ovarian cancer. The pembrolizumab-alone arm showed no benefit, indicating the PARP inhibitor drives the effect. OS remains immature.
Key Limitations
PFS primary endpoint with immature OS; the negative pembrolizumab-alone arm suggests benefit is attributable to olaparib rather than the checkpoint inhibitor; added toxicity and treatment-related deaths; contribution in the HRD-negative subset unclear; bevacizumab use was non-randomized.
Clinical Context
First-line maintenance olaparib is established for BRCA-mutated ovarian cancer, and bevacizumab+olaparib (PAOLA-1, HRD+) and niraparib cover broader populations. KEYLYNK-001 extends a pembrolizumab+olaparib maintenance strategy to BRCA non-mutated disease, but the negative pembrolizumab-alone arm and immature OS temper immediate practice change; regulatory positioning is pending.