Final overall survival results from EORTC 1333/PEACE-3 trial of enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer.

The primary endpoint was rPFS, while overall survival(OS) was a key secondary endpoint.

主要终点是rPFS，而总生存(OS)是一个关键的次要终点。

Interim OS results were reported at the time of primary analysis.

在主要分析时报告了中期总生存结果。

Here, we report the final OS analysis.

在这里，我们报告了最终的总生存分析结果。

patients_and_methods

From November 2015 to March 2023, 446 patients were randomly assigned to receive enzalutamide alone or enzalutamide combined with six cycles of Ra223.

从2015年11月至2023年3月，共有446名患者随机接受恩杂鲁胺单药治疗或恩杂鲁胺联合六周期的Ra223治疗。

Co-administration of bone-protecting agents (BPAs) became mandatory for all patients from March 2018.

从2018年3月起，所有患者必须联合使用骨保护剂(BPAs)。

Final analysis of OS was triggered on 1 May 2025.

总生存期(OS)的最终分析于2025年5月1日启动。

Results

With a median follow-up of 58 months and 317 reported deaths, the hazard ratio(HR) was 0.76 [95% confidence interval(CI) 0.60-0.96, P = 0.0096] for OS in favor of the enzalutamide + Ra223 arm, reaching the predefined level of statistical significance of <0.0248.

中位随访时间为58个月，共报告317例死亡，对于总生存期(OS)，恩杂鲁胺+Ra223治疗组的危险比(HR)为0.76 [95%置信区间(CI)为0.60-0.96，P=0.0096]，达到了预设的统计显著性水平<0.0248。

Median OS was 32.6 months (95% CI 29.3-38.2 months) in the enzalutamide arm (n = 224) and 38.2 months (95% CI 33.1-44.8 months) in the combination arm (n = 222).

恩杂鲁胺组的中位总生存期为32.6个月（95%置信区间29.3-38.2个月，n = 224），联合治疗组为38.2个月（95%置信区间33.1-44.8个月，n = 222）。

The HR for rPFS was 0.71 (95% CI 0.57-0.89).

无进展生存期的危险比为0.71（95%置信区间0.57-0.89）。

Grade ≥3 treatment-emergent adverse events (TEAEs) increased from 57.6% to 69.3% in the combination arm, as did treatment-related grade ≥3 TEAEs (18.8% versus 28.9%), with the most frequent being hypertension.

组合治疗组中3级或更高级别的治疗相关不良事件（TEAEs）发生率从57.6%增加到69.3%，治疗相关3级或更高级别的TEAEs发生率也从18.8%增加到28.9%，其中最常见的是高血压。

Conclusions

The final analysis of this study confirmed that the combination of enzalutamide with Ra223 significantly improved not only rPFS but also OS as first-line therapy for mCRPC versus enzalutamide alone.

该研究的最终分析证实，恩杂鲁胺联合Ra223作为mCRPC一线治疗，不仅显著改善了rPFS，而且显著改善了总生存期（OS），与单独使用恩杂鲁胺相比。

Co-administration of a BPA is required to reduce skeletal complications.

联合使用双膦酸盐类药物（BPA）是减少骨骼并发症所必需的。