Background

Enzalutamide and abiraterone acetate plus prednisone, which target the androgen receptor axis, have expanded the treatment of advanced prostate cancer. Retrospective analyses suggest some cross-resistance between these two drugs when used sequentially, but robust, prospective studies have not yet been reported.

Objective

To fulfil a regulatory postregistration commitment by evaluating the efficacy and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed following abiraterone acetate plus prednisone treatment.

Design, setting, and participants

Multicentre, single-arm, open-label study, enrolled patients with progressing mCRPC after ≥24 wk of abiraterone acetate plus prednisone treatment. All patients maintained castration therapy during the trial. Prior chemotherapy was allowed but not required.

Intervention

Patients received enzalutamide 160 mg/d orally.

Outcome measurements and statistical analysis

The primary endpoint was radiographic progression-free survival. Secondary endpoints were overall survival, prostate-specific antigen (PSA) response, and time-to-PSA progression. Safety data were also assessed. Kaplan-Meier methods were used to descriptively analyse time-to-event endpoints.

Results and limitations

Overall, 214 patients received enzalutamide treatment, 145 of whom were chemotherapy-naïve. Median radiographic progression-free survival was 8.1 mo (95% confidence interval: 6.1–8.3); median overall survival had not been reached. Unconfirmed PSA response rate was 27% (48 of 181). Median time-to-PSA progression was 5.7 mo (95% confidence interval: 5.6–5.8). The most common treatment-emergent adverse events were fatigue (32%), decreased appetite (25%), asthenia (18%), back pain (17%), and arthralgia (16%). No seizures were reported.

Conclusions

Enzalutamide showed antitumour activity in some patients with mCRPC who had previously progressed following ≥24 wk of abiraterone acetate plus prednisone treatment.

Patient summary

Patients with mCRPC who progressed on previous abiraterone acetate plus prednisone treatment, with or without prior chemotherapy, received enzalutamide. Although cross-resistance between the two agents was observed in a majority of patients, some still benefited from enzalutamide treatment.

中文翻译：

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恩扎鲁胺在欧洲曾接受醋酸阿比特龙+泼尼松治疗≥24周的转移性去势抵抗性前列腺癌患者的抗肿瘤活性和安全性

背景

恩扎鲁胺和醋酸阿比特龙加泼尼松靶向雄激素受体轴，已扩大了晚期前列腺癌的治疗范围。回顾性分析表明，当依次使用时，这两种药物之间存在交叉耐药性，但尚未进行有力的前瞻性研究。

客观的

为了通过评估enzalutamide在醋酸阿比特龙加泼尼松治疗后进展的转移性去势抵抗性前列腺癌（mCRPC）患者中的疗效和安全性，来完成注册后的监管承诺。

设计，设置和参与者

多中心，单臂，开放标签研究纳入了≥24 wk醋酸阿比特龙酯加泼尼松治疗后进展为mCRPC的患者。所有患者在试验期间均维持去势治疗。允许但不要求事先化疗。

干涉

患者口服恩杂鲁胺160 mg / d。

成果测量和统计分析

主要终点是影像学无进展生存期。次要终点是总体生存期，前列腺特异性抗原（PSA）反应和PSA转化时间。还评估了安全性数据。Kaplan-Meier方法用于描述性地分析事件发生时间的终点。

结果与局限性

总体而言，有214例患者接受了enzalutamide治疗，其中145例未经化疗。中位放射学无进展生存期为8.1 mo（95％置信区间：6.1–8.3）；尚未达到中位总体生存率。未确认的PSA应答率为27％（181个中的48个）。到PSA的时间中位数为5.7 mo（95％置信区间：5.6–5.8）。最常见的治疗性不良事件为疲劳（32％），食欲下降（25％），乏力（18％），背痛（17％）和关节痛（16％）。没有癫痫发作的报道。

结论

恩扎鲁胺在某些mCRPC患者中显示出抗肿瘤活性，这些患者先前≥24 wk醋酸阿比特龙加泼尼松治疗后已进展。

病人总结

曾接受醋酸阿比特龙酯加泼尼松治疗而进展的mCRPC患者，无论是否接受过化疗，均接受恩杂鲁胺治疗。尽管在大多数患者中观察到两种药物之间有交叉耐药性，但仍有一些患者受益于恩杂鲁胺治疗。