Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆
X H Wu, J Q Zhu, R T Yin, J X Yang, J H Liu, J Wang, L Y Wu, Z L Liu, Y N Gao, D B Wang, G Lou, H Y Yang, Q Zhou, B H Kong, Y Huang, L P Chen, G L Li, R F An, K Wang, Y Zhang, X J Yan, X Lu, W G Lu, M Hao, L Wang, H Cui, Q H Chen, G Abulizi, X H Huang, X F Tian, H Wen, C Zhang, J M Hou, M R Mirza, X H Wu, J Q Zhu, R T Yin, J X Yang, J H Liu, J Wang, L Y Wu, Z L Liu, Y N Gao, D B Wang, G Lou, H Y Yang, Q Zhou, B H Kong, Y Huang, L P Chen, G L Li, R F An, K Wang, Y Zhang, X J Yan, X Lu, W G Lu, M Hao, L Wang, H Cui, Q H Chen, G Abulizi, X H Huang, X F Tian, H Wen, C Zhang, J M Hou, M R Mirza
Abstract
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 III, 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 receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an 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: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (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 events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 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.
Keywords: maintenance therapy; niraparib; ovarian cancer.
Conflict of interest statement
Disclosure MRM has received fees for serving on advisory boards from Tesaro, GSK, Clovis Oncology, AstraZeneca, and Zai Lab and speaker fees from AstraZeneca, Tesaro, GSK, Zai Lab, and Roche. The other authors have declared no conflicts of interest. Data sharing From the publication date, upon reasonable request to the corresponding author (researchers who provide a methodologically sound proposal and assuming use of the data to meet the goals of this proposal), individual participant data that underlie the results reported in this article (text, tables, and figures) can be made available after de-identification. The study protocol can also be made available with reasonable request.
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Source: PubMed