Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial
Dr. Lucio Gordan's Thoughts
Another PARP-inhibitor in this setting with reasonable toxicity profile and flexibility of efficacy for patients with mutated or non-mutated BRCA status. More options of therapy may decrease cost of treatment in a competitive market.
PURPOSE
This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer.
PATIENTS AND METHODS
Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline BRCA 1/2 mutation.
RESULTS
Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided P < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline BRCA 1/2 mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count).
CONCLUSION
Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline BRCA 1/2 mutation, and showed a manageable safety profile.
Author Affiliations
1National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China.2Qilu Hospital of Shandong University, Jinan, China.3The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University (Hunan Cancer Hospital), Changsha, China.4Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.5Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.6Fudan University Shanghai Cancer Center, Shanghai, China.7Guangxi Medical University Cancer Hospital, Nanning, China.8Jiangsu Cancer Hospital, Nanjing, China.9Sun Yat-Sen University Cancer Center, Guangzhou, China.10The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.11West China Second University Hospital, Sichuan University, Chengdu, China/Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.12Harbin Medical University Cancer Hospital, Harbin, China.13The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China.14Sichuan Cancer Hospital, Chengdu, China.15Anhui Provincial Cancer Hospital, Hefei, China.16Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.17Shanghai General Hospital, Shanghai, China.18Beijing Cancer Hospital, Beijing, China.19Jiangxi Cancer Hospital, Nanchang, China.20Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China.21Liaoning Cancer Hospital & Institute, Shenyang, China.22The Second Hospital of Shanxi Medical University, Taiyuan, China.23Hubei Cancer Hospital, Wuhan, China.24Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.25Chongqing University Cancer Hospital, Chongqing, China.26Shanghai First Maternity and Infant Hospital, Shanghai, China.27The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.28Woman’s Hospital School of Medicine Zhejiang University, Hangzhou, China.29Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.30Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China.31Yunnan Cancer Hospital, Yunnan, China.32Peking University People’s Hospital, Beijing, China.33PLA General Hospital, Beijing, China.34The First Bethune Hospital of Jilin University, Changchun, China.35Jiangsu Hengrui Pharmaceuticals Co, Ltd, Shanghai, China.Related Articles
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