Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Center for Devices and Radiologic Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncologist. 2021 Feb;26(2):139-146. doi: 10.1002/onco.13585. Epub 2020 Nov 17.
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.
美国食品和药物管理局（FDA）于 2020 年 5 月加速批准了鲁卡帕尼用于治疗已接受雄激素受体靶向治疗和紫杉烷治疗的携带有害 BRCA 突变（种系和/或体细胞）相关转移性去势抵抗性前列腺癌（mCRPC）的成年患者。这一批准基于正在进行的多中心、开放性、单臂试验 TRITON2 的数据。符合上述标准的 62 名患者的主要终点——确认的客观缓解率为 44%（95%置信区间[CI]：31%-57%）。反应持续时间的中位数无法估计（95%CI：6.4 至无法估计）。56%的患者反应持续时间>6 个月，15%的患者反应持续时间>12 个月。鲁卡帕尼的安全性概况与聚（ADP-核糖）聚合酶酶抑制剂类药物以及其他鲁卡帕尼治疗卵巢癌的试验一致。因不良事件（AE）导致的死亡发生在 1.7%的患者中，8%的患者因 AE 停止使用鲁卡帕尼。发生 3-4 级 AE 的患者占 59%。没有前列腺癌患者发生骨髓增生异常综合征或急性髓系白血病。在 mCRPC 患者中进行的 TRITON3 试验正在进行中，计划验证鲁卡帕尼在 mCRPC 中的临床获益。本文总结了 FDA 的思维过程和支持这一加速批准的数据。对实践的意义：鲁卡帕尼加速批准用于治疗已接受雄激素受体靶向治疗和紫杉烷治疗的携带有害 BRCA 突变（种系和/或体细胞）相关转移性去势抵抗性前列腺癌的成年患者，这是为该选定患者群体批准的第一种治疗方法。这一批准基于一项单臂试验，该试验表明，与现有治疗方法相比，确认的客观缓解率更高，反应持续时间更长，毒性特征可接受。正在进行的 TRITON3 试验正在验证该药物的临床获益。
