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
Abstract
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.
Article Details
Authors (55)
Lingying Wu
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Jing Wang
Hunan Cancer Hospital Changsha China
Qingshui Li
Affiliated Cancer Hospital of Shandong First Medical University Jinan China
Danbo Wang
Cancer Hospital of China Medical University Liaoning Cancer Hospital and Institute Shenyang China
Cuiying Zhang
Inner Mongolia People's Hospital Hohhot China
Junying Tang
The First Affiliated Hospital of Chongqing Medical University Chongqing China
Guonan Zhang
Sichuan Cancer Hospital Chengdu China
Min Hao
Second Hospital of Shanxi Medical University Taiyuan China
Desheng Yao
Guangxi Medical University Cancer Hospital Nanning China
Qinglei Gao
Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology Wuhan China
Youzhong Zhang
Qilu Hospital of Shandong University Jinan China
Ruifang An
The First Affiliated Hospital of Xi’an Jiaotong University Xi’an China
Rutie Yin
Sichuan University West China Second Hospital Chengdu China
Li Wang
The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital Zhengzhou China
Bairong Xia
Anhui Provincial Cancer Hospital Hefei China
Qi Zhou
Chongqing University Cancer Hospital Chongqing China
Hongying Yang
Yunnan Cancer Hospital and The Third Affiliated Hospital of Kunming Medical University Kunming China
Jianqing Zhu
Zhejiang Cancer Hospital Hangzhou China
Kui Jiang
The Second Affiliated Hospital of Dalian Medical University Dalian China
Zhengzheng Chen
The First Affiliated Hospital of USTC Hefei China
Qiang Wu
Jiangsu Cancer Hospital Nanjing China
Wei Duan
Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing China
Yi Huang
Hubei Cancer Hospital Wuhan China
Hui Zhang
The Fourth Hospital of Hebei Medical University Shijiazhuang China
Shuqing Wei
Shanxi Cancer Hospital Taiyuan China
Guiling Li
Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
Yuanguang Meng
Seventh Medical Center of Chinese PLA General Hospital Beijing China
Ke Wang
Tianjin Medical University Cancer Institute and Hospital Tianjin China
Xinfeng Yang
Jiangxi Cancer Hospital Nanchang China
Xianghua Huang
The Second Hospital of Hebei Medical University Shijiazhuang China
Lingya Pan
Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Jinjin Yu
Jiangnan University Affiliated Hospital Wuxi China
Ge Lou
Cancer Hospital of Harbin Medical University Harbin China
Yu Zhang
Xiangya Hospital, Central South University Changsha China
Huaijun Zhou
Nanjing Drum Tower Hospital Nanjing China
Xiaoqing Guo
Shanghai First Maternity and Infant Hospital Shanghai China
Hong Yang
The First Affiliated Hospital of Air Force Military Medical University Xi’an China
Xiaodong Cheng
Women's Hospital School of Medicine Zhejiang University Hangzhou China
Xiumin Li
Linyi Cancer Hospital Linyi China
Wuliang Wang
The Second Affiliated Hospital of Zhengzhou University Zhengzhou China
Hongqin Zhao
The First Affiliated Hospital of Wenzhou Medical University Wenzhou China
Yunxia Li
General Hospital of Ningxia Medical University Yinchuan China
Yingjie Yang
The Affiliated Cancer Hospital of Guizhou Medical University Guiyang China
An Lin
Fujian Provincial Cancer Hospital Fuzhou China
Wenjun Cheng
The First Affiliated Hospital Nanjing Medical University Nanjing China
Lihong Chen
Shaanxi Provincial People's Hospital Xi’an China
Xiaoying Xie
The First Affiliated Hospital of Gannan Medical University Ganzhou China
Wen Di
Renji Hospital Affiliated with Shanghai Jiaotong University School of Medicine Shanghai China
Yuanjing Hu
Tianjin Central Hospital of Obstetrics and Gynecology Tianjin China
Mo Chen
Obstetrics and Gynecology Hospital of Fudan University Shanghai China
Hongwu Wen
Peking University First Hospital Beijing China
Liping Cai
The First Affiliated Hospital of Nanchang University Nanchang China
Xiaohua Wu
Fudan University Shanghai Cancer Center Shanghai China
Zhongqiu Lin
Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
Quanren Wang
Jiangsu Hengrui Pharmaceuticals Shanghai China