Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase 3 trial.
This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.In this phase 3, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2:1 to oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with bodyweight <77 kg or platelet count <150×103/μL received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was by interactive web response system and stratified by BRCA mutation, time-to-recurrence following penultimate chemotherapy and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.Between September 26, 2017 and February 2, 2019, 265 patients were randomized to niraparib (n=177) or placebo (n=88); 249 patients received an ISD (300 mg, n=14; 200 mg, n=235) per protocol. In the ITT population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 (95% CI, 10.9-not evaluable) versus 5.4 (95% CI, 3.7-5.7) months (HR=0.32; 95% CI, 0.23-0.45; p <0.0001), and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common were neutrophil count decreased (20.3 vs. 8.0%), and anemia (14.7 vs. 2.3%).Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.