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

Autor: Wu X; Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. wu.xh@fudan.edu.cn., Liu J; Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China., Wang J; Department of Gynecologic Cancer, Hunan Cancer Hospital, Central South University, Changsha, China., Wang L; Department of Gynecological Oncology, Affiliated Cancer Hospital of Zhengzhou University Henan Cancer Hospital, Zhengzhou, China., Lin Z; Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China., Wang X; Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China., Zhu J; Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou, China., Kong B; Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China., Fei J; Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China., Tang Y; Gynecological Oncology Center, Chongqing University Cancer Hospital, Chongqing, China., Xia B; Department of Gynecology and Oncology, Anhui Provincial Cancer Hospital, Anhui Provincial Hospital West District, Hefei, China., Liang Z; Department of Obstetrics and Gynecology, South West Hospital, The First Affiliated Hospital of Army Medical University, Chongqing, China., Wang K; Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China., Huang Y; Department of Gynecologic Oncology, Hubei Cancer Hospital, Wuhan, China., Zheng H; Department of Gynecologic Oncology, Beijing Cancer Hospital, Beijing, China., Lin A; Department of Gynecology, Fujian Provincial Cancer Hospital, Fuzhou, China., Jiang K; Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China., Wang W; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Wang X; Department of Oncology, Zhongshan Hospital of Xiamen University, Xiamen, China., Lou G; Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, China., Pan H; Department of Internal Medical Oncology, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China., Yao S; Department of Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Li G; Department of Gynecologic Oncology, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Hao M; Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan, China., Cai Y; Department of Obstetrics and Gynecology, Zhong Da Hospital, Southeast University, Nanjing, China., Chen X; Department of Gynecology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China., Yang Z; Department of Gynecologic Oncology, The Tumor Hospital Affiliated to Guangxi Medical University, Nanning, China., Chen Y; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China., Wen H; Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China., Qu P; Department of Gynecological Oncology, Tianjin Central Hospital of Obstetrics and Gynecology, Nankai, Tianjin, China., Xu C; IMPACT Therapeutics (Shanghai) Inc., Shanghai, China., Hsieh CY; IMPACT Therapeutics (Shanghai) Inc., Shanghai, China.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2024 Jun; Vol. 30 (6), pp. 1612-1621. Date of Electronic Publication: 2024 May 15.
DOI: 10.1038/s41591-024-03003-9
Abstrakt: 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 .
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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