机构：[1]National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.[2]Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.浙江省肿瘤医院[3]West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China.[4]Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.[5]Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.[6]Qilu Hospital of Shandong University, Jinan, China.[7]Peking University Cancer Hospital and Institute, Beijing, China.[8]Sun Yat-sen University Cancer Center, Guangzhou, China.[9]Fudan University Shanghai Cancer Center, Shanghai, China.[10]Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China.河南省肿瘤医院[11]Hubei Cancer Hospital (Affiliated Cancer Hospital of Tongji Medical College, Huazhong University of Science and Technology), Wuhan, China.[12]Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.[13]Chongqing University Cancer Hospital (Chongqing Cancer Hospital), Chongqing, China.[14]The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.[15]Cancer Hospital of China Medical University (Liaoning Cancer Hospital & Institute), Shenyang, China.[16]Women's Hospital School of Medicine Zhejiang University, Hangzhou, China.浙江大学医学院附属妇产科医院[17]Cancer Hospital of Fujian Medical University (Fujian Cancer Hospital), Fuzhou, China.[18]Harbin Medical University Cancer Hospital, Harbin, China.[19]Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.华中科技大学同济医学院附属协和医院[20]Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China.[21]The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, China.[22]Xiangya Hospital of Central South University, Changsha, China.[23]Zhongnan Hospital of Wuhan University, Wuhan, China.[24]Anhui Provincial Hospital (The First Affiliated Hospital of USTC), Hefei, China.[25]Second Hospital of Shanxi Medical University, Taiyuan, China.[26]The First Hospital of Jilin University, The First Hospital of Jilin University, Changchun, China.[27]Peking University People's Hospital, Beijing, China.[28]The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China.[29]The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.中山大学附属第一医院[30]Zai Lab (US) LLC, Boston, Massachusetts.[31]Zai Lab (Shanghai) Co, Ltd, Shanghai, China.
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.To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted).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.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.The primary end point was blinded, independent central review-assessed PFS in the intention-to-treat population.A total of 384 patients were randomized (255 niraparib [66.4%]; median [range] age, 53 [32-77] years; 129 placebo [33.6%]; median [range] 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 [HR], 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.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.ClinicalTrials.gov Identifier: NCT03709316.
基金：
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).
第一作者机构：[1]National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Li Ning,Zhu Jianqing,Yin Rutie,et al.Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial[J].JAMA ONCOLOGY.2023,9(9):1230-1237.doi:10.1001/jamaoncol.2023.2283.
APA：
Li Ning,Zhu Jianqing,Yin Rutie,Wang Jing,Pan Lingya...&Wu Lingying.(2023).Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial.JAMA ONCOLOGY,9,(9)
MLA：
Li Ning,et al."Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial".JAMA ONCOLOGY 9..9(2023):1230-1237
医学