Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial

被引：43

作者：

Li, Ning ^{[1
]}

Zhang, Youzhong ^{[2
]}

Wang, Jing ^{[3
]}

Zhu, Jianqing ^{[4
]}

Wang, Li ^{[5
]}

Wu, Xiaohua ^{[6
]}

Yao, Desheng ^{[7
]}

Wu, Qiang ^{[8
]}

Liu, Jihong ^{[9
]}

Tang, Junying ^{[10
]}

Yin, Rutie ^{[11
,12
]}

Lou, Ge ^{[13
]}

An, Ruifang ^{[14
]}

Zhang, Guonan ^{[15
]}

Xia, Xiaoping ^{[16
]}

Li, Qingshui ^{[17
]}

Zhu, Yaping ^{[18
]}

Zheng, Hong ^{[19
]}

Yang, Xinfeng ^{[20
]}

Hu, Yuanjing ^{[21
]}

Zhang, Xin ^{[22
]}

Hao, Min ^{[23
]}

Huang, Yi ^{[24
]}

Lin, Zhongqiu ^{[25
]}

Wang, Dong ^{[26
]}

Guo, Xiaoqing ^{[27
]}

Yao, Shuzhong ^{[28
]}

Wan, Xiaoyun ^{[29
]}

Zhou, Huaijun ^{[30
]}

Yao, Liangqing ^{[31
]}

Yang, Xielan ^{[32
]}

Cui, Heng ^{[33
]}

Meng, Yuanguang ^{[34
]}

Zhang, Songling ^{[35
]}

Qu, Jing ^{[36
]}

Zhang, Ben ^{[36
]}

Zou, Jianjun ^{[36
]}

Wu, Lingying ^{[1
]}

机构：

[1] Chinese Acad Med Sci, Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr,Natl Clin Res Ctr Canc, Beijing, Peoples R China

[2] Shandong Univ, Qilu Hosp, Jinan, Peoples R China

[3] Cent South Univ, Xiangya Sch Med, Affiliated Canc Hosp, Hunan Canc Hosp, Changsha, Peoples R China

[4] Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Hangzhou, Peoples R China

[5] Zhengzhou Univ, Henan Canc Hosp, Affiliated Canc Hosp, Zhengzhou, Peoples R China

[6] Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China

[7] Guangxi Med Univ Canc Hosp, Nanning, Peoples R China

[8] Jiangsu Canc Hosp, Nanjing, Peoples R China

[9] Sun Yat Sen Univ Canc Ctr, Guangzhou, Peoples R China

[10] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China

[11] Sichuan Univ, West China Second Univ Hosp, Chengdu, Peoples R China

[12] Sichuan Univ, West China Univ Hosp 2, Minist Educ, Key Lab Obstet & Gynecol & Pediat Dis & Birth Def, Chengdu, Peoples R China

[13] Harbin Med Univ Canc Hosp, Harbin, Peoples R China

[14] Xi An Jiao Tong Univ, Affiliated Hosp 1, Xian, Peoples R China

[15] Sichuan Canc Hosp, Chengdu, Peoples R China

[16] Anhui Prov Canc Hosp, Hefei, Peoples R China

[17] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Jinan, Peoples R China

[18] Shanghai Gen Hosp, Shanghai, Peoples R China

[19] Beijing Canc Hosp, Beijing, Peoples R China

[20] Jiangxi Canc Hosp, Nanchang, Jiangxi, Peoples R China

[21] Tianjin Cent Hosp Gynecol Obstet, Tianjin, Peoples R China

[22] Liaoning Canc Hosp & Inst, Shenyang, Peoples R China

[23] Shanxi Med Univ, Hosp 2, Taiyuan, Peoples R China

[24] Hubei Canc Hosp, Wuhan, Peoples R China

[25] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou, Peoples R China

[26] Chongqing Univ Canc Hosp, Chongqing, Peoples R China

[27] Shanghai First Matern & Infant Hosp, Shanghai, Peoples R China

[28] Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Peoples R China

[29] Zhejiang Univ, Womans Hosp, Sch Med, Hangzhou, Peoples R China

[30] Nanjing Univ Med Sch, Affiliated Hosp, Nanjing Drum Tower Hosp, Nanjing, Peoples R China

[31] Fudan Univ, Obstet & Gynecol Hosp, Shanghai, Peoples R China

[32] Yunnan Canc Hosp, Kunming, Yunnan, Peoples R China

[33] Peking Univ Peoples Hosp, Beijing, Peoples R China

[34] Peoples Liberat Army Gen Hosp, Beijing, Peoples R China

[35] Jilin Univ, Bethune Hosp 1, Changchun, Peoples R China

[36] Jiangsu Hengrui Pharmaceut Co Ltd, Shanghai, Peoples R China

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2022年 / 40卷 / 22期

关键词：

CANCER; PROGRESSION; INHIBITOR; SURVIVAL;

D O I：

10.1200/JCO.21.01511

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2436 / +

页数：18

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