TY - JOUR
T1 - Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA)
T2 - final overall survival analysis of a phase 3 randomised, placebo-controlled trial
AU - Wu, Xiaohua
AU - Zhu, Jianqing
AU - Yin, Rutie
AU - Yang, Jiaxin
AU - Liu, Jihong
AU - Wang, Jing
AU - Wu, Lingying
AU - Liu, Ziling
AU - Gao, Yunong
AU - Wang, Danbo
AU - Lou, Ge
AU - Yang, Hongying
AU - Zhou, Qi
AU - Kong, Beihua
AU - Huang, Yi
AU - Chen, Lipai
AU - Li, Guiling
AU - An, Ruifang
AU - Wang, Ke
AU - Zhang, Yu
AU - Yan, Xiaojian
AU - Lu, Xin
AU - Lu, Weiguo
AU - Hao, Min
AU - Wang, Li
AU - Cui, Heng
AU - Chen, Qionghua
AU - Abulizi, Guzhalinuer
AU - Huang, Xianghua
AU - Tian, Xiaofei
AU - Wen, Hao
AU - Huang, Zhao
AU - Dong, Juan
AU - Zhang, Charlie
AU - Hou, Jianmei
AU - Mirza, Mansoor R
N1 - © 2024 The Authors.
PY - 2024/6
Y1 - 2024/6
N2 - BACKGROUND: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) 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 gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm 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 × 103/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 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 gBRCAm; 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 gBRCAm status.FUNDING: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].
AB - BACKGROUND: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) 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 gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm 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 × 103/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 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 gBRCAm; 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 gBRCAm status.FUNDING: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].
UR - http://www.scopus.com/inward/record.url?scp=85192190065&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2024.102629
DO - 10.1016/j.eclinm.2024.102629
M3 - Journal article
C2 - 38745967
SN - 2589-5370
VL - 72
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 102629
ER -