FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA-Mutated Metastatic Castrate-Resistant Prostate Cancer
FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA-Mutated Metastatic Castrate-Resistant Prostate Cancer
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DOI：
10.1002/onco.13585
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发表时间：
2020-11-17
期刊：
影响因子：
5.8
通讯作者：
Beaver, Julia A.
中科院分区：
文献类型：
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作者：
Anscher, Mitchell S.;Chang, Elaine;Beaver, Julia A.
美国食品药品监督管理局（FDA）于2020年5月加速批准rucaparib用于治疗患有有害BRCA突变（生殖细胞和/或体细胞）相关转移性去势抵抗性前列腺癌（mCRPC）的成人患者，这些患者已接受雄激素受体导向疗法和紫杉烷治疗。该批准是基于正在进行的多中心、开放标签单组试验TRITON 2的数据。在符合上述标准的62例患者中，主要终点（确认的客观缓解率）为44%（95%置信区间[CI]：31%-57%）。中位缓解持续时间无法估计（95% CI：6.4至无法估计）。五十六%的患者的反应持续时间>6个月，15% >12个月。rucaparib的安全性特征与聚（ADP-核糖）聚合酶抑制剂类和rucaparib治疗卵巢癌的其他试验的安全性特征基本一致。1.7%的患者因不良事件（AE）死亡，8%的患者因AE停用rucaparib。59%的患者发生3-4级AE。没有前列腺癌患者发生骨髓增生异常综合征或急性髓性白血病。在mCRPC患者中进行的TRITON 3试验正在进行中，计划验证rucaparib在mCRPC中的临床获益。这篇文章总结了FDA的思维过程和数据支持这一加速approved.Implications实践的加速批准rucaparib用于治疗成人患者的有害BRCA突变（生殖细胞和/或体细胞）相关的转移性去势抵抗性前列腺癌谁已经与雄激素受体导向治疗和紫杉烷代表了第一个批准的治疗这一选定的患者群体。该批准是基于一项单臂试验，该试验证实了客观缓解率大于现有治疗，缓解持续时间有利，毒性特征可接受。正在进行的试验TRITON 3正在验证这种药物的临床益处。
The U.S. Food and Drug Administration (FDA) granted accelerated approval to rucaparib in May 2020 for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)-associated metastatic castrate-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane. This approval was based on data from the ongoing multicenter, open-label single-arm trial TRITON2. The primary endpoint, confirmed objective response rate, in the 62 patients who met the above criteria, was 44% (95% confidence interval [CI]: 31%-57%). The median duration of response was not estimable (95% CI: 6.4 to not estimable). Fifty-six percent of patients had a response duration of >6 months and 15% >12 months. The safety profile of rucaparib was generally consistent with that of the class of poly-(ADP-ribose) polymerase enzyme inhibitors and other trials of rucaparib in the treatment of ovarian cancer. Deaths due to adverse events (AEs) occurred in 1.7% of patients, and 8% discontinued rucaparib because of an AE. Grade 3-4 AEs occurred in 59% of patients. No patients with prostate cancer developed myelodysplastic syndrome or acute myeloid leukemia. The trial TRITON3 in patients with mCRPC is ongoing and is planned to verify the clinical benefit of rucaparib in mCRPC. This article summarizes the FDA thought process and data supporting this accelerated approval.Implications for Practice The accelerated approval of rucaparib for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)-associated metastatic castrate-resistant prostate cancer who have been treated with androgen receptor-directed therapy and a taxane represents the first approved therapy for this selected patient population. This approval was based on a single-arm trial demonstrating a confirmed objective response rate greater than that of available therapy with a favorable duration of response and an acceptable toxicity profile. The ongoing trial TRITON3 is verifying the clinical benefit of this drug.