Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation,UK.
Cancer Treat Rev. 2014 Feb;40(1):170-7. doi: 10.1016/j.ctrv.2013.06.008. Epub 2013 Aug 16.
Standard first-line treatment for metastatic castration-resistant prostate cancer (mCRPC) is docetaxel plus prednisone; however, patients will usually experience disease progression during or after docetaxel treatment due to inherent or acquired resistance. Before 2010, second-line options for mCRPC were limited. However, cabazitaxel, abiraterone acetate and enzalutamide have since been approved for patients with mCRPC whose disease has progressed during or after receiving docetaxel, based on the Phase III trials TROPIC, COU-AA-301 and AFFIRM. In all three trials, an overall survival benefit (primary endpoint) was seen in the experimental arm compared with the control arm: 15.1 vs. 12.7months for cabazitaxel plus prednisone compared with mitoxantrone plus prednisone in TROPIC (hazard ratio [HR] 0.70; P<0.0001); 14.8 vs. 10.9months for abiraterone acetateplus prednisone compared with placebo plus prednisone in COU-AA-301 (HR 0.65; P<0.001); and 18.4 vs. 13.6months for enzalutamide compared with placebo alone in AFFIRM (0.63; P<0.001). However, differences in patient populations, comparators, and selection and/or definition of secondary endpoints make it difficult to draw direct cross-trial comparisons. Radium-223 dichloride has also been approved for patients with mCRPC with metastases to bone but not other organs. To date, no comparative trials or sequencing studies with newer agents have been performed. Without such data, treatment decisions must be based on evaluation of the existing evidence. This commentary compares and contrasts study designs and key data from each of these Phase III trials, and also discusses recent and ongoing clinical trials with new agents in the first- and second-line settings in mCRPC.
转移性去势抵抗性前列腺癌（mCRPC）的标准一线治疗是多西他赛加泼尼松；然而，由于内在或获得性耐药，患者在接受多西他赛治疗期间或之后通常会出现疾病进展。在 2010 年之前，mCRPC 的二线选择有限。然而，自那时以来，卡巴他赛、醋酸阿比特龙和恩扎鲁胺已被批准用于在接受多西他赛治疗期间或之后疾病进展的 mCRPC 患者，这基于 III 期试验 TROPIC、COU-AA-301 和 AFFIRM。在所有这三项试验中，与对照组相比，实验组观察到总生存期获益（主要终点）：TROPIC 中卡巴他赛加泼尼松与米托蒽醌加泼尼松相比，为 15.1 个月比 12.7 个月（风险比 [HR] 0.70；P<0.0001）；COU-AA-301 中醋酸阿比特龙加泼尼松与安慰剂加泼尼松相比，为 14.8 个月比 10.9 个月（HR 0.65；P<0.001）；AFFIRM 中恩扎鲁胺与安慰剂相比，为 18.4 个月比 13.6 个月（0.63；P<0.001）。然而，由于患者人群、比较药物、次要终点的选择和/或定义的不同，使得难以进行直接的试验间比较。镭-223 二氯化物也已被批准用于有骨转移但无其他器官转移的 mCRPC 患者。迄今为止，尚未进行与新药物比较的试验或序贯研究。在没有这些数据的情况下，治疗决策必须基于对现有证据的评估。本评论比较和对比了这些 III 期试验中的每个试验的研究设计和关键数据，并讨论了最近和正在进行的一线和二线治疗 mCRPC 的新药物的临床试验。
