European Urology ( IF 25.3 ) Pub Date : 2017-08-23 , DOI: 10.1016/j.eururo.2017.07.035 Johann S. de Bono , Simon Chowdhury , Susan Feyerabend , Tony Elliott , Enrique Grande , Amal Melhem-Bertrandt , Benoit Baron , Mohammad Hirmand , Patrick Werbrouck , Karim Fizazi
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:
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。