新型雄激素受体通路靶向药物在去势抵抗性前列腺癌治疗中的作用：基于随机试验的文献荟萃分析。

Role of the novel generation of androgen receptor pathway targeted agents in the management of castration-resistant prostate cancer: A literature based meta-analysis of randomized trials.

机构信息

Department of Molecular and Translational Medicine, University of Brescia, 25123, Brescia, Italy; Molecular Therapy and Pharmacogenomic Unit, ASST di Cremona, Viale Concordia 1, 26100, Cremona, Italy.

Department of Molecular and Translational Medicine, University of Brescia, 25123, Brescia, Italy.

出版信息

Eur J Cancer. 2016 Jul;61:111-21. doi: 10.1016/j.ejca.2016.04.002. Epub 2016 May 7.

DOI:10.1016/j.ejca.2016.04.002

PMID:27162152

Abstract

BACKGROUND

Several novel androgen receptor pathway targeted agents have recently entered on to therapeutic landscape for metastatic castration-resistant prostate cancer (CRPC). We performed a meta-analysis to assess the effect of these novel androgen receptor pathway targeted agents in improving outcome of CRPC patients.

METHODS

A literature-based meta-analysis of randomized controlled trials (RCTs) in accordance with the preferences for reported items in systematic reviews and meta-analyses guidelines was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology meetings were searched. The primary outcome was overall survival. The secondary end-points were time to the first symptomatic skeletal event, progression-free survival, prostatic antigen specific (PSA) response rate, time to PSA progression and safety.

RESULTS

Pooled analysis from RCTs of novel androgen receptor pathway targeted agents revealed significantly increased overall survival compared with placebo or prednisone (hazard ratio [HR] for death: 0.79, 95% confidence interval [CI]: 0.71-0.87; P < 0.00001). All secondary end-points favoured the androgen receptor pathway targeted agents, although heterogeneity was high in some cases. The pooled analysis revealed that the androgen receptor pathway targeted agents significantly improved time to the first skeletal event (HR = 0.69, 95% CI: 0.63-0.75; P < 0.00001), progression-free survival (HR = 0.48, 95% CI: 0.37-0.62; P < 0.00001), time to PSA progression (HR = 0.37, 95% CI: 0.24-0.59; P < 0.0001) and PSA response rate (relative risk [RR] = 4.46, 95% CI: 2.63-7.55; P < 0.00001). The incidence of grade ≥3 adverse events was moderately higher with androgen receptor pathway targeted agents as compared with the control arms (RR = 1.11, 95% CI: 0.98-1.25; P = 0.09).

CONCLUSION

This study confirmed the efficacy and safety of the novel androgen receptor pathway targeted agents.

摘要

背景

几种新型雄激素受体通路靶向药物最近已进入转移性去势抵抗性前列腺癌（CRPC）的治疗领域。我们进行了一项荟萃分析，以评估这些新型雄激素受体通路靶向药物在改善 CRPC 患者结局方面的疗效。

方法

根据系统评价和荟萃分析报告项目偏好原则，对随机对照试验（RCT）进行文献基础的荟萃分析。从 PubMed、Cochrane 图书馆和美国临床肿瘤学会会议摘要中检索相关文献。主要结局是总生存期。次要终点是首次有症状骨骼事件的时间、无进展生存期、前列腺抗原特异性（PSA）反应率、PSA 进展时间和安全性。

结果

新型雄激素受体通路靶向药物 RCT 的汇总分析显示，与安慰剂或泼尼松相比，总生存期显著延长（死亡风险比 [HR]：0.79，95%置信区间 [CI]：0.71-0.87；P<0.00001）。所有次要终点均有利于雄激素受体通路靶向药物，尽管在某些情况下存在高度异质性。汇总分析显示，雄激素受体通路靶向药物显著改善了首次骨骼事件时间（HR=0.69，95%CI：0.63-0.75；P<0.00001）、无进展生存期（HR=0.48，95%CI：0.37-0.62；P<0.00001）、PSA 进展时间（HR=0.37，95%CI：0.24-0.59；P<0.0001）和 PSA 反应率（相对风险 [RR]：4.46，95%CI：2.63-7.55；P<0.00001）。与对照组相比，雄激素受体通路靶向药物的 3 级及以上不良事件发生率略高（RR=1.11，95%CI：0.98-1.25；P=0.09）。