Enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer: results of the EORTC 1333/PEACE-3 trial.

materials_and_methods

From November 2015 to March 2023, 446 patients, including 11 who received abiraterone, were randomized to enzalutamide (without placebo) or enzalutamide combined with six cycles of Ra223.

从2015年11月到2023年3月，共有446名患者（包括11名接受阿比特龙治疗的患者）被随机分配接受恩杂鲁胺（无安慰剂）或恩杂鲁胺联合六个周期的Ra223治疗。

As of March 2018, the co-administration of zoledronic acid or denosumab was mandatory.

截至2018年3月，联合使用唑来膦酸或地舒单抗是强制性的。

The primary endpoint was radiological progression-free survival(rPFS) by investigator assessment.

主要终点是通过研究者评估的放射学无进展生存期（rPFS）。

Key secondary endpoints included overall survival(OS), time to subsequent systemic treatment, pain progression, and symptomatic skeletal event.

主要次要终点包括总生存（OS）、后续系统治疗时间、疼痛进展和症状性骨事件。

Results

The hazard ratio(HR) for rPFS was 0.69 [95% confidence interval(CI) 0.54-0.87, P = 0.0009], with a median rPFS of 16.4 months (95% CI 13.8-19.2 months) in the enzalutamide arm and 19.4 months (95% CI 17.1-25.3 months) in the combination arm.

无进展生存期（rPFS）的风险比（HR）为0.69 [95%置信区间（CI）0.54-0.87，P = 0.0009]，恩杂鲁胺组的中位无进展生存期为16.4个月（95% CI 13.8-19.2个月），联合治疗组为19.4个月（95% CI 17.1-25.3个月）。

At the preplanned interim analysis conducted at 80% of the OS events, the HR for OS was 0.69 (95% CI 0.52-0.90, P = 0.0031), with a median OS of 35.0 months (95% CI 28.8-38.9 months) in the enzalutamide arm and 42.3 months (95% CI 36.8-49.1 months) in the combination arm.

在预先计划的中期分析中，当总生存事件达到80%时，总生存的危险比为0.69（95%置信区间0.52-0.90，P = 0.0031），恩杂鲁胺组的中位总生存期为35.0个月（95%置信区间28.8-38.9个月），联合治疗组的中位总生存期为42.3个月（95%置信区间36.8-49.1个月）。

Due to non-proportional hazards, this will be tested further at the final OS analysis.

由于风险比例不一致，将在最终总生存分析中进一步测试。

Treatment-emergent adverse events (TEAEs) ≥ grade 3 were recorded in 55.8% and 65.6% of the patients in the enzalutamide and combination arms, respectively.

在恩杂鲁胺组和联合治疗组中，分别有55.8%和65.6%的患者记录了≥3级的治疗相关不良事件（TEAEs）。

The most frequent grade ≥3 TEAEs in the combination arm were hypertension (34%), fatigue (6%), fracture (5%), anemia (5%), and neutropenia (5%).

联合治疗组中最常见的≥3级TEAEs是高血压（34%）、疲劳（6%）、骨折（5%）、贫血（5%）和中性粒细胞减少症（5%）。

Fractures [either treatment-emergent or post-treatment, symptomatic or pathologic, or with or without bone-protecting agent (BPA) use] were reported in 30 (13.4%) patients in the enzalutamide arm and 53 patients (24.3%) in the combination arm.

在恩杂鲁胺组中，有30名（13.4%）患者报告出现骨折（无论是治疗后出现的、治疗期间出现的、有症状的、病理性骨折，还是使用或未使用骨保护剂（BPA））；而在联合治疗组中，有53名患者（24.3%）报告出现骨折。

Conclusions

PEACE-3 demonstrates that combining enzalutamide with Ra223 as first-line therapy for mCRPC significantly improves rPFS.

PEACE-3研究显示，将恩杂鲁胺与Ra223联合作为转移性去势抵抗性前列腺癌一线治疗显著改善了放射学无进展生存期（rPFS）。

Although statistically significant at the OS interim boundary, the study will continue to the final OS analysis.

尽管在总生存期（OS）中期分析中具有统计学意义，研究将继续进行最终的总生存期分析。