Background
Phase III RCT (PRIMA/ENGOT-OV26/GOG-3012). 733 patients with newly diagnosed advanced (stage III-IV) high-grade serous or endometrioid ovarian cancer who had complete or partial response to first-line platinum-based chemotherapy (unselected for BRCA/HRD). Randomized 2:1 to niraparib 300 mg QD maintenance (with individualized starting dose 200 mg QD for patients <77 kg or platelet count <150×10⁹/L) vs placebo. Treatment continued until progression or unacceptable toxicity. Niraparib is an oral PARP1/2 inhibitor. Prospectively stratified by HRD status (BRCAm/HRd vs HRp).
Interventions and follow up
Arm A: Niraparib 300 mg QD (or 200 mg QD per individualized starting dose) maintenance until progressio
Arm B: Placebo
Primary endpoint: PFS in HRd population (BRCAm + non-BRCAm HRd), then overall populatio
mFollow up: 13.8 month
Arm B: Placebo
Primary endpoint: PFS in HRd population (BRCAm + non-BRCAm HRd), then overall populatio
mFollow up: 13.8 month
Results
Median PFS — HRd population: 21.9 months (niraparib) vs 10.4 months (placebo), HR 0.43 (95% CI 0.31–0.59), P<.001
Median PFS — overall population: 13.8 vs 8.2 months, HR 0.62 (95% CI 0.50–0.76), P<.001
Median PFS — BRCAm subgroup: Not reached vs 8.2 months, HR 0.40
Median PFS — HRp subgroup: 8.1 vs 5.4 months, HR 0.68 (95% CI 0.49–0.94)
Median PFS — overall population: 13.8 vs 8.2 months, HR 0.62 (95% CI 0.50–0.76), P<.001
Median PFS — BRCAm subgroup: Not reached vs 8.2 months, HR 0.40
Median PFS — HRp subgroup: 8.1 vs 5.4 months, HR 0.68 (95% CI 0.49–0.94)
Adverse events
Main adverse events: Grade ≥3 thrombocytopenia: 28.7% (niraparib) vs 0.5% (placebo) — most common dose-limiting toxicity. Grade ≥3 anemia: 31.3% vs 0.5%. Grade ≥3 neutropenia: 12.8% vs 1.2%. Individualized starting dose reduced grade ≥3 hematologic toxicity vs fixed 300 mg QD in prior trial (NOVA). Discontinuation due to AEs: 12% vs 3%.
Conclusions
Niraparib maintenance significantly improved PFS across all populations (HRd, overall) in newly diagnosed ovarian cancer, supporting its use as first-line maintenance regardless of HRD/BRCA status, with greatest benefit in HRd/BRCAm patients.
Key Limitations
Key Limitations: OS data immature at primary analysis. The individualized starting dose (200 vs 300 mg) was introduced to reduce thrombocytopenia — not prospectively randomized. HRd testing (Myriad myChoice CDx) is complex and not universally available. Thrombocytopenia remains a clinically meaningful toxicity requiring dose modifications in ~30% of patients. Patients with HRp tumors had a more modest PFS benefit (HR 0.68).
Clinical Context
PRIMA led to FDA approval of niraparib as first-line maintenance for all advanced ovarian cancer patients who respond to platinum-based chemotherapy (regardless of HRD status) in 2020. However, in clinical practice, the greatest benefit is in BRCA-mutated and HRd patients. PAOLA-1 (olaparib + bevacizumab) is typically preferred for patients who received bevacizumab in first-line treatment. Niraparib is preferred when bevacizumab was not used.
References