Fuzuloparib with or without apatinib as maintenance therapy in newly diagnosed, advanced ovarian cancer (FZOCUS‐1): A multicenter, randomized, double‐blind, placebo‐controlled phase 3 trial
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Although poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPis) and bevacizumab were approved as first-line maintenance for advanced ovarian cancer (OC), evidence comparing this combination with PARPi monotherapy, especially in BRCA-mutated/homologous recombination-deficient (HRD) patients, is lacking. This study compared combined fuzuloparib (a PARPi) plus apatinib (a vascular endothelial growth factor receptor-2 inhibitor) with either fuzuloparib or placebo as first-line maintenance in patients with advanced OC. Patients who had newly diagnosed, advanced OC and responded to first-line, platinum-based chemotherapy were randomized 2:2:1 to receive combined fuzuloparib (100 mg twice daily) plus apatinib (375 mg daily), fuzuloparib (150 mg twice daily) plus placebo, or double-placebo treatment. The primary end point was blinded independent review committee (BIRC)-assessed progression-free survival (PFS). Six hundred seventy-four patients were randomized to receive fuzuloparib plus apatinib (n = 269), fuzuloparib (n = 269), or placebo (n = 136). At the final analysis (November 1, 2024; 385 BIRC-assessed PFS events; median follow-up, 40 months), the median BIRC-assessed PFS was 26.9 months with the combination versus placebo (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.44-0.75; one-sided p < .0001) and 29.9 months with fuzuloparib monotherapy versus placebo (HR, 0.58; 95% CI, 0.44-0.75; one-sided p < .0001) compared with 11.1 months with placebo. A PFS benefit was observed regardless of germline BRCA1/2 mutation status. In homologous recombination-deficient patients (including those with BRCA1/2 mutations), combined fuzuloparib and apatinib produced a PFS similar to that of fuzuloparib (34.1 vs. 35.8 months, respectively); in homologous recombination-proficient patients, PFS had a trend favoring the combination (16.6 vs. 11.0 months; HR, 0.73; 95% CI, 0.45-1.19). Both treatments were well tolerated. Overall survival was immature. Both fuzuloparib and combination therapy improved PFS compared with placebo as maintenance therapy for patients who had newly diagnosed, advanced OC. Adding apatinib to fuzuloparib did not prolong PFS among homologous recombination-deficient patients. There was a PFS benefit trend among homologous recombination-proficient patients who received combination therapy compared with those who received monotherapy.
DOI: 10.3322/caac.70042
Authors: Lingying Wu, Jing Wang, Qingshui Li, Danbo Wang, Cuiying Zhang, Junying Tang, Guonan Zhang, Min Hao, Desheng Yao, Qinglei Gao, Youzhong Zhang, Ruifang An, Rutie Yin, Li Wang, Bairong Xia, Qi Zhou, Hongying Yang, Jianqing Zhu, Kui Jiang, Zhengzheng Chen, Qiang Wu, Wei Duan, Yi Huang, Hui Zhang, Shuqing Wei, Guiling Li, Yuanguang Meng, Ke Wang, Xinfeng Yang, Xianghua Huang, Lingya Pan, Jinjin Yu, Ge Lou, Yu Zhang, Huaijun Zhou, Xiaoqing Guo, Hong Yang, Xiaodong Cheng, Xiumin Li, Wuliang Wang, Hongqin Zhao, Yunxia Li, Yingjie Yang, An Lin, Wenjun Cheng, Lihong Chen, Xiaoying Xie, Wen Di, Yuanjing Hu, Mo Chen, Hongwu Wen, Liping Cai, Xiaohua Wu, Zhongqiu Lin, Quanren Wang, Xinfeng Yang, Ning Li
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Cancer Hospital of Chinese Academy of Medical Sciences, Hunan Cancer Hospital, Shandong First Medical University, Liaoning Cancer Hospital & Institute, China Medical University, Inner Mongolia People's Hospital, The Affiliated Yongchuan Hospital of Chongqing Medical University, Sichuan Cancer Hospital, Shanxi Medical University, Second Hospital of Shanxi Medical University, Guangxi Medical University, Tumor Hospital of Guangxi Medical University, Tongji Hospital, Huazhong University of Science and Technology, Xiangya Hospital Central South University, Qilu Hospital of Shandong University, First Affiliated Hospital of Xi'an Jiaotong University, Sichuan University, West China Second University Hospital of Sichuan University, Zhengzhou University, Henan Cancer Hospital, Chongqing University, Chongqing Cancer Hospital, Kunming Medical University, Air Force Medical University, Zhejiang Cancer Hospital, Second Affiliated Hospital of Dalian Medical University, University of Science and Technology of China, Jiangsu Cancer Hospital, Capital Medical University, Beijing Obstetrics and Gynecology Hospital, Hubei Cancer Hospital, Hebei Medical University, Fourth Hospital of Hebei Medical University, Shanxi Provincial Cancer Hospital, Wuhan Union Hospital, Chinese PLA General Hospital, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Jiangxi Provincial Cancer Hospital, Jiangsu Hengrui Medicine (China), Second Hospital of Hebei Medical University, Jiangnan University, Wuxi Fourth People's Hospital, Harbin Medical University, Third Affiliated Hospital of Harbin Medical University, Nanjing Drum Tower Hospital, Shanghai First Maternity and Infant Hospital, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang University, Second Affiliated Hospital of Zhengzhou University, First Affiliated Hospital of Wenzhou Medical University, Ningxia Medical University, Ningxia Medical University General Hospital, Guiyang Medical University, Affiliated Hospital of Guizhou Medical University, Fujian Provincial Cancer Hospital, Jiangsu Province Hospital, Nanjing Medical University, Shaanxi Provincial People's Hospital, Gannan Medical University, First Affiliated Hospital of Gannan Medical University, Shanghai Jiao Tong University, Renji Hospital, Tianjin Central Hospital of Gynecology Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Peking University First Hospital, First Affiliated Hospital of Nanchang University, Fudan University Shanghai Cancer Center, Sun Yat-sen University, Sun Yat-sen Memorial Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,330
OpenAlex ID: W4416673826