Background
Phase III, double-blind, placebo-controlled RCT. 733 patients with newly diagnosed advanced ovarian cancer (stage III/IV) who achieved complete or partial response after first-line platinum-based chemotherapy. Enrolled regardless of BRCA/HRD status. Randomized 2:1 to niraparib or placebo.
Interventions and follow up
Arm A: Niraparib once daily (individualized starting dose: 300 mg if ≥77 kg and platelets ≥150×10&sup9;/L; otherwise 200 mg)
Arm B: Placebo
Primary endpoint: PFS in HRD-positive population, then overall population
mFollow up: 13.8 months
Arm B: Placebo
Primary endpoint: PFS in HRD-positive population, then overall population
mFollow up: 13.8 months
Results
mPFS (HRD+, 50.9%): 21.9 vs 10.4 months (Arm A vs Arm B), HR 0.43, 95%CI 0.31-0.59, P<.001
mPFS (overall): 13.8 vs 8.2 months, HR 0.62, 95%CI 0.50-0.76, P<.001
mPFS (HRD-/non-BRCA-mut, ~30%): 8.1 vs 5.4 months, HR 0.68
mPFS (overall): 13.8 vs 8.2 months, HR 0.62, 95%CI 0.50-0.76, P<.001
mPFS (HRD-/non-BRCA-mut, ~30%): 8.1 vs 5.4 months, HR 0.68
Adverse events
Hematologic (grade ≥3, Arm A vs Arm B): thrombocytopenia 28.6% vs 1.2%; anemia 30.6% vs 2.4%; neutropenia 12.8% vs 1.2%
Tolerability: individualized dosing reduced hematologic toxicity vs fixed 300 mg dosing; treatment discontinuation 14.7% vs 2.7% (Arm A vs Arm B)
Tolerability: individualized dosing reduced hematologic toxicity vs fixed 300 mg dosing; treatment discontinuation 14.7% vs 2.7% (Arm A vs Arm B)
Conclusions
Niraparib maintenance significantly prolonged PFS in newly diagnosed advanced ovarian cancer in both HRD-positive and unselected populations, making it applicable across all-comers regardless of biomarker status.
Key Limitations
Benefit is modest in HRD-negative patients (HR 0.68, ~3 months absolute gain), raising questions about clinical meaningfulness in this subgroup. Significant hematologic toxicity (thrombocytopenia, anemia) requires frequent CBC monitoring. OS data immature. Individualized dosing based on weight/platelets was pragmatic but introduced variability in drug exposure.
Clinical Context
FDA approved 2020 for first-line maintenance of advanced ovarian cancer after platinum-based chemotherapy, regardless of BRCA/HRD status - the broadest label of any first-line PARP inhibitor. ESMO-MCBS: A for HRD+ population. PARP inhibitor choice (olaparib, niraparib, rucaparib) is now guided by biomarker status: BRCA mut favors olaparib; HRD+ BRCA-wt allows any PARP +/- bevacizumab; HRD- shows modest niraparib benefit.