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

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.

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Journal
CA A Cancer Journal for Clinicians
Published
2025-11-25
DOI
https://doi.org/10.3322/caac.70042
Citations
1
Primary Topic
PARP inhibition in cancer therapy
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article
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1.05
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article

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

Hong Yang, Jinjin Yu, Danbo Wang, Liping Cai et al.
1 citations
CA A Cancer Journal for Clinicians
PARP inhibition in cancer therapy
1.05
article

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

Hong Yang, Jinjin Yu, Danbo Wang, Liping Cai, Jianqing Zhu, Desheng Yao, Xiumin Li, Wen J. Di, Xiaoqing Guo, Guonan Zhang, Shuqing Wei, Ke Wang, Qinglei Gao, Min Hao, Yingjie Yang, Junying Tang, Wenjun Cheng, Quanren Wang, Qingshui Li, Bairong Xia, Xianghua Huang, Wei Duan, Youzhong Zhang, Lingying Wu, Ge Lou, Cuiying Zhang, Wuliang Wang, Rutie Yin, Hui Zhang, Li Wang, Ning Li, Mo Chen, Yu Zhang, Yunxia Li, Qi Zhou, Guiling Li, Xiaohua Wu, Lihong Chen, Qiang Wu, Hongying Yang, Hongwu Wen, Xinfeng Yang, Xiaoying Xie, Jing Wang, Hongqin Zhao, Yuanguang Meng, Yuanjing Hu, Yi Huang, Huaijun Zhou, Lin An, Ruifang An, Zhongqiu Lin, Kui Jiang, Xiaodong Cheng, Zhengzheng Chen, Lingya Pan
article en
1 citations

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.

CA A Cancer Journal for CliniciansVol. 76(1)
Hebei Medical University (CN), Jiangnan University (CN), Central South University (CN), Nanchang University (CN), Guiyang Medical University (CN), Harbin Medical University (CN), Sun Yat-sen University (CN), Chongqing University (CN), Guangxi Medical University (CN), Shanxi Medical University (CN), Capital Medical University (CN), Dalian Medical University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Sichuan University (CN), Kunming Medical University (CN), Wenzhou Medical University (CN), Renji Hospital (CN), Peking Union Medical College Hospital (CN), First Affiliated Hospital of Wenzhou Medical University (CN), Tianjin Medical University Cancer Institute and Hospital (CN), Chinese PLA General Hospital (CN), Zhengzhou University (CN), West China Second University Hospital of Sichuan University (CN), Shaanxi Provincial People's Hospital (CN), Fudan University Shanghai Cancer Center (CN), Jiangxi Provincial Cancer Hospital (CN), Sun Yat-sen Memorial Hospital (CN), Zhejiang Cancer Hospital (CN), Second Hospital of Hebei Medical University (CN), Second Affiliated Hospital of Dalian Medical University (CN), Guizhou Cancer Hospital (CN), Shanxi Provincial Cancer Hospital (CN), Third Affiliated Hospital of Harbin Medical University (CN), Fourth Hospital of Hebei Medical University (CN), Nanjing Drum Tower Hospital (CN), Second Affiliated Hospital of Zhengzhou University (CN), Wuxi Fourth People's Hospital (CN), Hunan Cancer Hospital (CN), Sichuan Cancer Hospital (CN), First Affiliated Hospital of Xi'an Jiaotong University (CN), Inner Mongolia People's Hospital (CN), Tianjin Central Hospital of Gynecology Obstetrics (CN), Ningxia Medical University (CN), Jiangsu Cancer Hospital (CN), Wuhan Union Hospital (CN), Anhui Provincial Hospital (CN), The Affiliated Yongchuan Hospital of Chongqing Medical University (CN), Peking University First Hospital (CN), Second Hospital of Shanxi Medical University (CN), First Affiliated Hospital of Gannan Medical University (CN), Women's Hospital, School of Medicine, Zhejiang University (CN), Ningxia Medical University General Hospital (CN), Henan Cancer Hospital (CN), Obstetrics and Gynecology Hospital of Fudan University (CN), Jiangsu Hengrui Medicine (China) (CN), Fujian Provincial Cancer Hospital (CN), Shanghai First Maternity and Infant Hospital (CN), Chongqing Cancer Hospital (CN), Xijing Hospital (CN), Xiangya Hospital Central South University (CN), Tongji Hospital (CN), Shanxi Provincial People’s Hospital (CN), Hubei Cancer Hospital (CN), Liaoning Cancer Hospital & Institute (CN), Qilu Hospital of Shandong University (CN), Shandong First Medical University (CN), Beijing Obstetrics and Gynecology Hospital (CN), First Affiliated Hospital of Nanchang University (CN), Huazhong University of Science and Technology (CN), Nanjing Medical University (CN), Chongqing Medical University (CN), China Medical University (CN), Air Force Medical University (CN)
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