Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): fi nal overall survival analysis of a phase 3 randomised, placebo-controlled trial

Background Niraparib significantly prolonged progression -free survival versus placebo in patients with platinumsensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (g BRCA m) status, in NORA. This analysis reports final data on overall survival (OS). Methods This randomised, double-blind, placebo -controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with g BRCA m) and had received >= 2 prior lines of platinum -based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with strati fi cation by g BRCA m status, time to recurrence following penultimate platinum -based chemotherapy, and response to last platinum -based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 x 10 (3) / mu L at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8 - 61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4 - 58.9) versus 47.6 (33.3 - not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60 - 1.23), in the overall population; 56.0 (36.1 - NE) versus 47.6 (31.6 - NE) months, with HR of 0.86 (95% CI, 0.46 - 1.58), in patients with g BRCA m; and 46.5 (41.0 - NE) versus 46.9 (31.8 - NE) months, with HR of 0.87 (95% CI, 0.56 - 1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of g BRCA m status.