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
Mené sur 265 patientes atteintes d'un cancer de l'ovaire sensible aux sels de platine et récidivant, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du niraparib dispensé en traitement d'entretien par doses personnalisées
Background : 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. Patients and methods : 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. Results
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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%). Conclusions : 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.
Annals of Oncology 2021