National 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.
Qilu Hospital of Shandong University, Jinan, China.
J Clin Oncol. 2022 Aug 1;40(22):2436-2446. doi: 10.1200/JCO.21.01511. Epub 2022 Apr 11.
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 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 mutation.
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 < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline 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).
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 mutation, and showed a manageable safety profile.
这项 III 期临床试验旨在探索氟唑帕利（原称氟唑帕利）作为二线或后线铂类化疗后应答的维持治疗，在铂类敏感、复发性高级别卵巢癌患者中的疗效和安全性。
既往接受至少两种铂类方案治疗的铂类敏感、复发性卵巢癌患者，按照 2:1 的比例被分配接受氟唑帕利（150mg，每日两次）或匹配安慰剂，每 28 天为一个周期。主要终点是盲法独立评审委员会（BIRC）评估的总人群无进展生存期（PFS）和种系 突变亚组人群的 BIRC 评估的 PFS。
2019 年 4 月 30 日至 2020 年 1 月 10 日期间，共有 252 例患者被随机分配至氟唑帕利（n=167）或安慰剂（n=85）组。截至 2020 年 7 月 1 日，BIRC 评估的总人群中，氟唑帕利治疗的中位 PFS 显著改善（风险比[HR]，0.25；95%置信区间[CI]，0.17 至 0.36；单侧 ＜.0001），优于安慰剂组。来自预设亚组分析的 HR 显示，种系 突变患者（HR，0.14；95%CI，0.07 至 0.28）或无突变患者（HR，0.46；95%CI，0.29 至 0.74）均有一致的获益趋势。氟唑帕利组报告的最常见的≥3 级治疗相关不良事件为贫血（25.1%）、血小板计数下降（16.8%）和中性粒细胞计数下降（12.6%）。仅有 1 例患者（0.6%）因治疗相关毒性（白细胞计数和中性粒细胞计数同时下降）而停止使用氟唑帕利。
氟唑帕利作为维持治疗，与安慰剂相比，在铂类敏感、复发性卵巢癌患者中，无论是否存在种系 突变，均显著改善了 PFS，并具有可管理的安全性。
