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

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

Affiliations

  • 1 Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. wu.xh@fudan.edu.cn.
  • 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 .

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