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

作者：Xiaohua Wu, Jianqing Zhu, Rutie Yin, Jiaxin Yang, Jihong Liu, Jing Wang, Lingying Wu, Ziling Liu, Yunong Gao, Danbo Wang, Ge Lou, Hongying Yang, Qi Zhou, Beihua Kong, Yi Huang, Lipai Chen, Guiling Li, Ruifang An, Ke Wang, Yu Zhang, Xiaojian Yan, Xin Lü, Weiguo Lu, Min Hao, Li Wang, Heng Cui, Qionghua Chen, Guzhalinuer Abulizi, Xianghua Huang, Xiaofei Tian, Hao Wen, Zhao Huang, Juan Dong, Charlie Zhang, Jianmei Hou, Mansoor Raza Mirza · 发表于：EClinicalMedicine · 年份：2024 · DOI：10.1016/j.eclinm.2024.102629 · 被引用次数：24 · 研究领域：PARP inhibition in cancer therapy、Ovarian cancer diagnosis and treatment、Toxin Mechanisms and Immunotoxins

Background Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, 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 stratification 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 × 10 3 /μL 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...