Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer

Author:

Li Ning1,Zhu Jianqing2,Yin Rutie3,Wang Jing4,Pan Lingya5,Kong Beihua6,Zheng Hong7,Liu Jihong8,Wu Xiaohua9,Wang Li10,Huang Yi11,Wang Ke12,Zou Dongling13,Zhao Hongqin14,Wang Chunyan15,Lu Weiguo16,Lin An17,Lou Ge18,Li Guiling19,Qu Pengpeng20,Yang Hongying21,Zhang Yu22,Cai Hongbing23,Pan Yueyin24,Hao Min25,Liu Ziling26,Cui Heng27,Yang Yingjie28,Yao Shuzhong29,Zhen Xiaoa30,Hang Wenzhao31,Hou Jianmei31,Wang Juan31,Wu Lingying1

Affiliation:

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

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

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

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

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

30. Zai Lab (US) LLC, Boston, Massachusetts

31. Zai Lab (Shanghai) Co, Ltd, Shanghai, China

Abstract

ImportanceThe 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.ObjectiveTo evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted).Design, Setting, and ParticipantsThis 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.InterventionsPatients 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 MeasurementsThe primary end point was blinded, independent central review–assessed PFS in the intention-to-treat population.ResultsA 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.Conclusion and RelevanceThis 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

Publisher

American Medical Association (AMA)

Subject

Oncology,Cancer Research

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