FDA Approval Summary: Niraparib plus Abiraterone Acetate Fixed-Dose Combination for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer.

Substantial evidence of effectiveness was demonstrated by cohort 1 of MAGNITUDE (NCT03748641), a multi-cohort study.

MAGNITUDE（NCT03748641）研究的第1队列显示了显著的有效性证据，这是一项多队列研究。

Cohort 1 was a double-blindtrial that randomly assigned 423 patients with metastatic castration-resistant prostate cancer and homologous recombination repair mutations to receive niraparib 200 mg daily plus AA 1,000 mg daily and prednisone versus placebo plus AAP.

队列 1 是一项双盲试验，随机分配了 423 名患有转移性去势抵抗性前列腺癌且具有同源重组修复突变的患者，接受每日 200 mg 的尼拉帕利加每日 1,000 mg 的阿比特龙和泼尼松治疗，与安慰剂加 AAP 相比。

The presence of BRCAm was a stratification factor.

BRCAm 的存在是一个分层因素。

There was a statistically significant improvement in the primary endpoint of radiographic progression-free survival(rPFS) by blinded independent central review in the BRCAm subpopulation: the median rPFS was 16.6 months [95% confidence interval(CI), 13.9-not estimable] in the niraparib + AAP arm and 10.9 months (95% CI, 8.3-13.8) in the placebo + AAP arm (HR, 0.53; 95% CI, 0.36-0.79; P = 0.0014).

在BRCAm亚组中，通过盲法独立中央审查的影像学无进展生存期（rPFS）的主要终点有统计学显著改善：niraparib + AAP组的中位rPFS为16.6个月[95%置信区间（CI），13.9-无法估计]，而安慰剂 + AAP组为10.9个月（95% CI, 8.3-13.8）（HR, 0.53; 95% CI, 0.36-0.79; P = 0.0014）。

There was also a statistically significant improvement in rPFS in the all-homologous recombination repair mutation population (intention-to-treatpopulation); however, exploratory analyses conducted by the FDA indicated that this improvement was primarily attributed to the subgroup of patients with BRCAm, which supported limiting the indication to that population.

在所有同源重组修复突变人群中，rPFS也有统计学显著改善（意向治疗人群）；然而，美国食品药品监督管理局进行的探索性分析表明，这种改善主要归因于BRCAm亚组的患者，这支持将适应症限制在该人群。

Adding niraparib to AAP resulted in increased toxicity, including anemia requiring transfusion in 27% of patients.

在 AAP 中加入 niraparib 增加了毒性，包括27%的患者需要输血的贫血。

This article summarizes the data and the FDA's thought process supporting the traditional approval of niraparib plus AA fixed-dose combination.

本文总结了支持 niraparib 加 AA 固定剂量组合传统批准的数据和 FDA 的思考过程。