Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial

  • Nat Med. 2024 Jun;30(6):1612-1621. doi: 10.1038/s41591-024-03003-9.
Xiaohua Wu  #  1 ,  Jihong Liu  #  2 ,  Jing Wang  3 ,  Li Wang  4 ,  Zhongqiu Lin  5 ,  Xiaobin Wang  6 ,  Jianqing Zhu  7 ,  Beihua Kong  8 ,  Junwei Fei  9 ,  Ying Tang  10 ,  Bairong Xia  11 ,  Zhiqing Liang  12 ,  Ke Wang  13 ,  Yi Huang  14 ,  Hong Zheng  15 ,  An Lin  16 ,  Kui Jiang  17 ,  Wei Wang  18 ,  Xin Wang  19 ,  Ge Lou  20 ,  Hongming Pan  21 ,  Shuzhong Yao  22 ,  Guiling Li  23 ,  Min Hao  24 ,  Yunlang Cai  25 ,  Xuejun Chen  26 ,  Zhijun Yang  27 ,  Youguo Chen  28 ,  Hongwu Wen  29 ,  Pengpeng Qu  30 ,  Cong Xu  31 ,  Chih-Yi Hsieh  31 ,  FLAMES Investigators
Affiliations
  • 1. Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. [email protected].
  • 2. Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • 3. Department of Gynecologic Cancer, Hunan Cancer Hospital, Central South University, Changsha, China.
  • 4. Department of Gynecological Oncology, Affiliated Cancer Hospital of Zhengzhou University Henan Cancer Hospital, Zhengzhou, China.
  • 5. Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
  • 6. Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
  • 7. Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
  • 8. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China.
  • 9. Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.
  • 10. Gynecological Oncology Center, Chongqing University Cancer Hospital, Chongqing, China.
  • 11. Department of Gynecology and Oncology, Anhui Provincial Cancer Hospital, Anhui Provincial Hospital West District, Hefei, China.
  • 12. Department of Obstetrics and Gynecology, South West Hospital, The First Affiliated Hospital of Army Medical University, Chongqing, China.
  • 13. Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  • 14. Department of Gynecologic Oncology, Hubei Cancer Hospital, Wuhan, China.
  • 15. Department of Gynecologic Oncology, Beijing Cancer Hospital, Beijing, China.
  • 16. Department of Gynecology, Fujian Provincial Cancer Hospital, Fuzhou, China.
  • 17. Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
  • 18. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 19. Department of Oncology, Zhongshan Hospital of Xiamen University, Xiamen, China.
  • 20. Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, China.
  • 21. Department of Internal Medical Oncology, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 22. Department of Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 23. Department of Gynecologic Oncology, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 24. Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan, China.
  • 25. Department of Obstetrics and Gynecology, Zhong Da Hospital, Southeast University, Nanjing, China.
  • 26. Department of Gynecology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • 27. Department of Gynecologic Oncology, The Tumor Hospital Affiliated to Guangxi Medical University, Nanning, China.
  • 28. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • 29. Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
  • 30. Department of Gynecological Oncology, Tianjin Central Hospital of Obstetrics and Gynecology, Nankai, Tianjin, China.
  • 31. IMPACT Therapeutics (Shanghai) Inc., Shanghai, China.
  • # Contributed equally.
PMID: 38750351 DOI: 10.1038/s41591-024-03003-9
Abstract

Poly(Adenosine diphosphate-ribose) polymerase (PARP) inhibitors as maintenance therapy after first-line chemotherapy have improved progression-free survival in women with advanced ovarian cancer; however, not all PARP inhibitors can provide benefit for a biomarker-unselected population. Senaparib is a PARP Inhibitor that demonstrated antitumor activity in patients with solid Tumors, including Ovarian Cancer, in phase 1 studies. The multicenter, double-blind, phase 3 trial FLAMES randomized (2:1) 404 females with advanced Ovarian Cancer (International Federation of Gynecology and Obstetrics stage III-IV) and response to first-line platinum-based chemotherapy to senaparib 100 mg (n = 271) or placebo (n = 133) orally once daily for up to 2 years. The primary endpoint was progression-free survival assessed by blinded independent central review. At the prespecified interim analysis, the median progression-free survival was not reached with senaparib and was 13.6 months with placebo (hazard ratio 0.43, 95% confidence interval 0.32-0.58; P < 0.0001). The benefit with senaparib over placebo was consistent in the subgroups defined by BRCA1 and BRCA2 mutation or homologous recombination status. Grade ≥3 treatment-emergent adverse events occurred in 179 (66%) and 27 (20%) patients, respectively. Senaparib significantly improved progression-free survival versus placebo in patients with advanced Ovarian Cancer after response to first-line platinum-based chemotherapy, irrespective of BRCA1 and BRCA2 mutation status and with consistent benefits observed between homologous recombination subgroups, and was well tolerated. These results support senaparib as a maintenance treatment for patients with advanced Ovarian Cancer after a response to first-line chemotherapy. ClinicalTrials.gov identifier: NCT04169997 .

Products