Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Efficacy and safety of niraparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer using an individualized starting dose (PRIME Study): A randomized, double-blind, placebo-controlled, phase 3 trial (#216)

Ning Li 1 , Jianqing Zhu 2 , Rutie Yin 3 , Jing Wang 4 , Lingya Pan 5 , Beihua Kong 6 , Hong Zheng 7 , Jihong Liu 8 , Xiaohua Wu 9 , Li Wang 10 , Yi Huang 11 , Ke Wang 12 , Dongling Zou 13 , Hongqin Zhao 14 , Chunyan Wang 15 , Weiguo Lu 16 , An Lin 17 , Ge Lou 18 , Guiling Li 19 , Pengpeng Qu 20 , Hongying Yang 21 , Xiaoa Zhen 22 , Wenzhao Hang 23 , Jianmei Hou 23 , Ashish Banerjee 24 , Lingying Wu 1
  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 & 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
  21. The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, China
  22. Zai Lab (US) LLC, Boston
  23. Zai Lab (Shanghai) Co., Ltd, Shanghai, China
  24. GSK, Melbourne, Australia

Aims

The PRIME study (NCT03709316) evaluated the efficacy and safety of niraparib using an individualized starting dose as maintenance treatment following complete or partial response (CR/PR) to first-line (1L) platinum-based chemotherapy (CT) in Chinese patients with advanced ovarian cancer (OC).

Methods

In this double-blind, placebo-controlled, phase 3 study, patients with newly diagnosed, advanced (stage III–IV) OC were randomized 2:1 to niraparib or placebo after CR/PR to 1L CT. The study aimed to recruit 381 patients. Patients in the niraparib arm received 200 mg once daily, except patients with baseline body weight ≥77 kg and platelet count ≥150,000/μL who received 300 mg once daily. Patients were stratified by germline BRCA (gBRCA) status, tumor homologous recombination deficiency/proficiency (HRd/HRp) status, neoadjuvant chemotherapy, and best response to 1L CT. Primary endpoint was progression-free survival (PFS); secondary endpoint included overall survival (OS). All efficacy outcomes were analyzed based on the intention-to-treat population.

Results

Of 384 randomized patients (niraparib, n=255; placebo, n=129), 125 (32.6%) were gBRCA-mutated and 257 (66.9%) were HRd. Median follow-up was 27.5 months. Median PFS was significantly longer in patients receiving niraparib compared with placebo (24.8 vs 8.3 months; HR 0.45; 95% CI 0.34–0.60; P<0.001). Treatment benefit was demonstrated in HRd-subgroup (HR 0.48; 95% CI 0.34–0.68; P<0.001) and HRp-subgroup (HR 0.41; 95% CI 0.25–0.65; P<0.001) subgroups. OS data was immature (HR 0.63; 95% CI 0.38–1.03; P=0.061). The most common grade ≥3 adverse events in the niraparib arm were anemia (18.0%), neutrophil count decreased (17.3%) and platelet count decreased (14.1%).

Conclusions

This phase 3 study is the first to confirm the efficacy and safety of niraparib in Chinese patients with advanced OC. Niraparib resulted in a clinically meaningful and significant PFS improvement over placebo, regardless of biomarker status. Niraparib was well tolerated, and no new safety signals were identified.

  1. This work was previously presented at Society of Gynecologic Oncology, March 2022; submitted with permission and on behalf of the original authors. The study was funded Zai Lab (Shanghai) Co. Ltd. This work was also partially supported by the National Major Scientific and Technological Special Project for ‘Significant New Drugs Development’ in 2020, China [grant number 2020ZX09101 014]. ClinicalTrials.gov identifier: NCT03709316 Third-party medical writing support: Writing and editorial support, funded by GlaxoSmithKline and coordinated by Rebecca Crawford, PhD, of GlaxoSmithKline, was provided by Sanuji Gajamange, PhD, and Joyce Lee, PhD, of Meditech Media (Sydney, Australia), part of Nucleus Global.