Question  Does treatment with niraparib prolong progression-free survival in patients with newly diagnosed advanced ovarian cancer?

Finding  In the PRIME phase 3 randomized clinical trial of 384 patients with newly diagnosed advanced ovarian cancer after receiving first-line platinum-based chemotherapy, including those who underwent R0 resection at primary debulking surgery, treatment with niraparib with an individualized starting dose significantly extended progression-free survival vs placebo and reduced the risk of disease progression or death by 55%.

Meaning  The results of this randomized clinical trial support niraparib monotherapy as a standard of care after first-line platinum-based chemotherapy in a broad patient population with advanced ovarian cancer.

Importance  The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease.

Objective  To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted).

Design, Setting, and Participants  This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months.

Interventions  Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×10³/μL [to convert to ×10⁹/μL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy.

Main Outcomes and Measurements  The primary end point was blinded, independent central review–assessed PFS in the intention-to-treat population.

Results  A total of 384 patients were randomized (255 niraparib [66.4%]; median age, 53 [32-77] years; 129 placebo [33.6%]; median age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio , 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events.

Conclusion and Relevance  This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting.

Trial RegistrationClinicalTrials.gov Identifier: NCT03709316  

Accepted for Publication: May 4, 2023.

Published Online: July 13, 2023. doi:10.1001/jamaoncol.2023.2283

Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2023 Li N et al. JAMA Oncology.

Corresponding Author: Lingying Wu, MD, PhD, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nali, Chaoyang District, Beijing 100021, China (wulingying@csco.org.cn).

Author Contributions: Dr L. Wu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs N. Li, Zhu, and Yin are co–first authors and contributed equally to the manuscript.

Concept and design: N. Li, Jing Wang, X. Wu, Zhen, Hang, Hou, L. Wu.

Acquisition, analysis, or interpretation of data: All authors.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: N. Li, Zhen, Hang, Hou.

Obtained funding: L. Wu.

Administrative, technical, or material support: N. Li, Zhu, Yin, Jing Wang, L. Pan, Kong, Zheng, J. Liu, X. Wu, L. Wang, Huang, K. Wang, Zou, Zhao, C. Wang, Lu, Lin, Lou, G. Li, Qu, H. Yang, Zhang, Cai, Y. Pan, Hao, Z. Liu, Cui, Y. Yang, Yao, Zhen, Hang, Juan Wang, L. Wu.

Supervision: Hou, L. Wu.

Conflict of Interest Disclosures: Drs Zhen, Hang, Hou, and Juan Wang reported being employees of and holding shares and stock options in Zai Lab during the conduct of the study. Dr L. Wu reported grants from Zai Lab during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was funded by Zai Lab (Shanghai) Co, Ltd, and partially supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development in 2020 (China; grant 2020ZX09101-014).

Role of the Funder/Sponsor: The study sponsor, Zai Lab, supported the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Meeting Presentations: Results from this study were presented in part as oral presentations at the 2022 Society of Gynecologic Oncology (SGO) Annual Meeting (Phoenix, Arizona; March 18-21, 2022), European Society for Medical Oncology (ESMO) Gynaecological Cancers Congress 2022 (Valencia, Spain; June 17-18, 2022), and ESMO Gynaecological Cancers Congress 2023 (Valencia, Spain; January 23-24, 2023), and as posters at the 2022 American Society of Clinical Oncology Annual Meeting (ASCO; Chicago, Illinois; June 3-7, 2022), the 2022 International Gynecologic Cancer Society Annual Global Meeting (New York, New York; September 29-October 1, 2022), 2023 SGO Annual Meeting (Tampa, Florida; March 25-28, 2023), and the 2023 ASCO Annual Meeting (Chicago, Illinois; June 2-6, 2023).

Data Sharing Statement: See Supplement 4.

Additional Contributions: We thank the patients, the investigators, and their teams who took part in this study. Zai Lab provided funding for third-party writing assistance for this article from Jinlong Guo, PhD, Costello Medical. He did not receive any additional compensation beyond his usual salary.