尼拉帕尼、醋酸阿比特龙加强的松治疗转移性去势抵抗性前列腺癌：3期量级试验的最终总生存期分析

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology Pub Date : 2025-08-01 DOI:10.1016/j.euo.2025.04.012

Kim N. Chi , Elena Castro , Gert Attard , Matthew R. Smith , Shahneen Sandhu , Eleni Efstathiou , Guilhem Roubaud , Eric J. Small , Andrea Pereira de Santana Gomes , Dana E. Rathkopf , Marniza Saad , Howard Gurney , Wonho Jung , Won Kim , Shiva Dibaj , Daphne Wu , Jenny Zhang , Angela Lopez-Gitlitz , Peter Francis , David Olmos

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Rathkopf , Marniza Saad , Howard Gurney , Wonho Jung , Won Kim , Shiva Dibaj , Daphne Wu , Jenny Zhang , Angela Lopez-Gitlitz , Peter Francis , David Olmos","doi":"10.1016/j.euo.2025.04.012","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and objective</h3><div>The phase 3 MAGNITUDE trial previously met its primary endpoint of an improvement in radiographic progression-free survival with niraparib + abiraterone acetate and prednisone (AAP) versus placebo + AAP in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in genes involved in DNA homologous recombination repair (HRR<sup>+</sup>), particularly in <em>BRCA1/2</em>.</div></div><div><h3>Methods</h3><div>Patients were prospectively screened for HRR alterations and randomized 1:1 to niraparib + AAP (<em>n</em> = 212) or placebo + AAP (<em>n</em> = 211). 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引用次数: 0

摘要

背景和目的：3期量级试验之前达到了其主要终点，即在转移性阉切抵抗性前列腺癌（mCRPC）和参与DNA同源重组修复（HRR+）的基因改变的患者中，尼拉帕尼+醋酸阿比特龙和泼尼松（AAP）与安慰剂+ AAP相比，放射学无进展生存率的改善，特别是在BRCA1/2中。方法：对患者进行HRR改变的前瞻性筛选，并以1:1的比例随机分配到尼拉帕尼+ AAP （n = 212）或安慰剂+ AAP （n = 211）。我们报告的结果来自预先指定的、事件驱动的、次要疗效终点的最终分析。主要发现和局限性：中位随访37.3个月的最终分析显示，在HRR+人群中，尼拉帕尼+ AAP与安慰剂+ AAP的总生存期（OS）无差异(风险比[HR] 0.931, 95%可信区间[CI] 0.720-1.203；p = 0.585)或BRCA1/2改变亚组(HR 0.788, 95% CI 0.554-1.120；名义p = 0.183)。调整基线预后因素的预先指定多变量分析显示，在HRR+人群中，尼拉帕尼+ AAP比安慰剂+ AAP有更长的生存期趋势(HR 0.785, 95% CI 0.606-1.016；名义p = 0.066)和BRCA1/2亚组(HR 0.663, 95% CI 0.464-0.947；名义p = 0.024)。在HRR+人群中，尼拉帕尼+ AAP在症状进展时间上具有统计学意义，具有临床意义的改善(HR 0.547, 95% CI 0.396-0.754；p = 0.006)和BRCA1/2亚组(HR 0.562, 95% CI 0.371-0.849；名义p = 0.006)，在HRR+人群中，到细胞毒性化疗的时间有临床意义的改善(HR 0.688, 95% CI 0.499-0.950；p = 0.022)和BRCA1/2亚组(HR 0.598, 95% CI 0.387-0.924；名义p = 0.019)，与安慰剂+ AAP相比。尼拉帕尼+ AAP的安全性在更长时间的随访中保持不变；不良事件主要是血液学和可控的。结论和临床意义：MAGNITUDE最终分析显示，HRR+ mCRPC患者，包括那些已批准brca改变mCRPC适应症的患者，与安慰剂+ AAP相比，一般继续从尼拉帕尼+ AAP一线治疗中获益。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Niraparib and Abiraterone Acetate plus Prednisone in Metastatic Castration-resistant Prostate Cancer: Final Overall Survival Analysis for the Phase 3 MAGNITUDE Trial

Background and objective

The phase 3 MAGNITUDE trial previously met its primary endpoint of an improvement in radiographic progression-free survival with niraparib + abiraterone acetate and prednisone (AAP) versus placebo + AAP in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in genes involved in DNA homologous recombination repair (HRR⁺), particularly in BRCA1/2.

Methods

Patients were prospectively screened for HRR alterations and randomized 1:1 to niraparib + AAP (n = 212) or placebo + AAP (n = 211). We report results from the prespecified, event-driven, final analysis of secondary efficacy endpoints.

Key findings and limitations

Final analysis at median follow-up of 37.3 mo revealed no difference in overall survival (OS) between niraparib + AAP and placebo + AAP in the HRR⁺ population (hazard ratio [HR] 0.931, 95% confidence interval [CI] 0.720–1.203; p = 0.585) or the subgroup with BRCA1/2 alterations (HR 0.788, 95% CI 0.554–1.120; nominal p = 0.183). Prespecified multivariate analyses adjusted for baseline prognostic factors showed a trend toward longer OS with niraparib + AAP over placebo + AAP in the HRR⁺ population (HR 0.785, 95% CI 0.606–1.016; nominal p = 0.066) and the BRCA1/2 subgroup (HR 0.663, 95% CI 0.464–0.947; nominal p = 0.024). Niraparib + AAP led to a statistically significant, clinically meaningful improvement in time to symptomatic progression in both the HRR⁺ population (HR 0.547, 95% CI 0.396–0.754; p = 0.006) and the BRCA1/2 subgroup (HR 0.562, 95% CI 0.371–0.849; nominal p = 0.006), and a clinically meaningful improvement in time to cytotoxic chemotherapy in the HRR⁺ population (HR 0.688, 95% CI 0.499–0.950; p = 0.022) and the BRCA1/2 subgroup (HR 0.598, 95% CI 0.387–0.924; nominal p = 0.019) in comparison to placebo + AAP. The niraparib + AAP safety profile remains unchanged at longer follow-up; adverse events were primarily hematologic and manageable.

Conclusions and clinical implications

The MAGNITUDE final analysis showed that patients with HRR⁺ mCRPC, including those with the approved indication of BRCA-altered mCRPC, generally continue to benefit from first-line treatment with niraparib + AAP in comparison to placebo + AAP.

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来源期刊

European urology oncology Multiple-

CiteScore

15.50

自引率

2.40%

发文量

128

审稿时长

20 days

期刊介绍： Journal Name: European Urology Oncology Affiliation: Official Journal of the European Association of Urology Focus: First official publication of the EAU fully devoted to the study of genitourinary malignancies Aims to deliver high-quality research Content: Includes original articles, opinion piece editorials, and invited reviews Covers clinical, basic, and translational research Publication Frequency: Six times a year in electronic format