FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer
正文 · 中文译文
FDA批准尼拉帕利与醋酸阿比特龙联合泼尼松用于BRCA2突变转移性去势敏感性前列腺癌 癌症批准 肿瘤（癌症）/血液系统恶性肿瘤批准通知 进行中 | 癌症加速批准 已证实临床获益 | 癌症加速批准 已撤回 | 癌症加速批准 其他 | 癌症加速批准 2025年12月12日，美国食品药品监督管理局（FDA）批准尼拉帕利与醋酸阿比特龙（Akeega，Janssen Biotech， Inc.）联合泼尼松，用于经FDA批准的检测确定为有害或疑似有害BRCA2突变（BRCA2m）的转移性去势敏感性前列腺癌（mCSPC）成人患者。 Akeega的完整处方信息将发布在Drugs@FDA上。 疗效与安全性 疗效在AMPLITUDE（NCT04497844）中进行了评估，这是一项随机、双盲试验，纳入696例同源重组修复（HRR）基因突变（HRRm）的mCSPC患者。患者按1:1随机接受尼拉帕利与醋酸阿比特龙联合泼尼松（AAP）或安慰剂联合AAP。所有患者同时接受持续雄激素剥夺治疗。 主要疗效结局指标为研究者评估的影像学无进展生存期（rPFS）。总生存期（OS）为另一项疗效结局。 该试验显示，在携带HRRm的患者总体人群中，与安慰剂联合AAP相比，尼拉帕利联合AAP在rPFS方面表现出具有统计学意义的改善。在一项针对323例BRCA2m患者的探索性分析中，尼拉帕利联合AAP组rPFS的风险比（HR）为0.46（95% CI：0.32，0.66），中位rPFS不可估计[NE]（95% CI：41，NE），安慰剂联合AAP组为26个月（95% CI：18，28）。在一项针对373例非BRCA2m患者的探索性分析中，rPFS的HR为0.88（95% CI：0.63，1.24），表明总体改善主要归因于BRCA2m患者中所见的结果。 在OS的首次中期分析中，BRCA2m人群已发生91例死亡，其中尼拉帕利联合AAP组36例（22%），安慰剂联合AAP组55例（34%）。 处方信息包括以下警告和注意事项：骨髓增生异常综合征/急性髓系白血病；骨髓抑制；低钾血症；液体潴留和心血管不良反应；肝毒性；肾上腺皮质功能不全；低血糖症；与镭Ra 223二氯化物联合使用时骨折和死亡率增加；可逆性后部脑病综合征；以及胚胎-胎儿毒性。 推荐剂量为尼拉帕利200 mg和阿比特龙醋酸酯1，000 mg口服，每日一次，联合泼尼松5 mg每日一次，直至疾病进展或出现不可接受的毒性。患者还应同时接受促性腺激素释放激素（GnRH）类似物治疗，或应已接受双侧睾丸切除术。 加速审批程序 本综述使用了评估辅助工具（Assessment Aid），这是申请人自愿提交的材料，旨在便于FDA进行评估。 本申请获得了优先审评资格。FDA加速程序在《行业指南：严重疾病药物和生物制品的加速程序》中有相关描述。 医疗保健专业人员应将所有怀疑与任何药物和器械使用相关的严重不良事件报告至FDA的MedWatch报告系统，或致电1-800-FDA-1088。 如需获取研究性肿瘤产品单患者IND方面的协助，医疗保健专业人员可联系OCE的Project Facilitate，电话240-402-0004，或发送电子邮件至OncProjectFacilitate@fda.hhs.gov。 在X上关注肿瘤卓越中心：@FDAOncology。 内容更新日期： 2025年12月12日 受监管产品 药物 肿瘤学
正文 · 英文原文
FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer Cancer Approvals Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals On December 12, 2025, the Food and Drug Administration approved niraparib and abiraterone acetate (Akeega, Janssen Biotech, Inc.) with prednisone for adults with deleterious or suspected deleterious BRCA2-mutated (BRCA2m) metastatic castration-sensitive prostate cancer (mCSPC), as determined by an FDA-approved test. Full prescribing information for Akeega will be posted on Drugs@FDA. Efficacy and Safety Efficacy was evaluated in AMPLITUDE (NCT04497844), a randomized, double-blind trial in 696 patients with homologous recombination repair (HRR) gene-mutated (HRRm) mCSPC. Patients were randomized (1:1) to receive niraparib and abiraterone acetate plus prednisone (AAP) or placebo and AAP. All patients also received continued androgen deprivation therapy. The major efficacy outcome measure was investigator-assessed radiographic progression-free survival (rPFS). Overall survival (OS) was an additional efficacy outcome. The trial demonstrated a statistically significant improvement in rPFS for niraparib and AAP compared to placebo and AAP in the overall population of patients with HRRm. In an exploratory analysis of 323 patients with BRCA2m, the hazard ratio (HR) for rPFS was 0.46 (95% CI: 0.32, 0.66) with median rPFS not estimable [NE] (95% CI: 41, NE) for niraparib and AAP and 26 months (95% CI: 18, 28) for placebo and AAP. In an exploratory analysis in 373 patients with non-BRCA2m, the HR for rPFS was 0.88 (95% CI: 0.63, 1.24), indicating that the overall improvement was primarily attributed to the results seen in patients with BRCA2m. At the first interim analysis for OS, 91 deaths had occurred in the BRCA2m population, including 36 (22%) on the niraparib and AAP arm and 55 (34%) on the placebo and AAP arm. The prescribing information includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia; myelosuppression; hypokalemia; fluid retention, and cardiovascular adverse reactions; hepatoxicity; adrenocortical insufficiency; hypoglycemia; increased fractures and mortality in combination with radium Ra 223 dichloride; posterior reversible encephalopathy syndrome; and embryo-fetal toxicity. The recommended dose is 200 mg niraparib and 1,000 mg abiraterone acetate orally once daily in combination with 5 mg prednisone once daily until disease progression or unacceptable toxicity. Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. Expedited Programs This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. Follow the Oncology Center of Excellence on X: @FDAOncology. Content current as of: 12/12/2025 Regulated Product(s) Drugs Oncology
摘要 待译
On December 12, 2025, the Food and Drug Administration approved niraparib and abiraterone acetate (Akeega, Janssen Biotech, Inc.) with prednisone for adults with deleterious or suspected deleterious BRCA2-mutated (BRCA2m) metastatic castration-sensitive prostate cancer.