Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Urology, Aichi Medical University Hospital, Nagakute, Japan.
Prostate. 2020 Nov;80(15):1373-1380. doi: 10.1002/pros.24069. Epub 2020 Sep 11.
The optimal sequential therapy for castration-resistant prostate cancer (CRPC) remains unknown. In recent years, some doubts have emerged regarding the clinical benefit of sequential therapy with androgen receptor axis-targeted agents (ART) such as abiraterone (ABI) or enzalutamide (ENZ) for patients with CRPC. We compared the effect of ART-to-ART (AA) sequential therapy after castration resistance with that of docetaxel (DTX)-combined sequential therapy (ART to DTX or DTX to ART) in patients with CRPC.
We retrospectively identified and analyzed the data of 315 patients with CRPC treated in our seven affiliated institutions between 2009 and 2019. All patients received either DTX or ART (ABI or ENZ) as the first- or second-line therapy after castration resistance. We compared the overall survival (OS) and the second progression-free survival (PFS2), calculated from the initiation of first-line therapy after castration resistance, between the AA sequence group and the DTX-combined sequence group. PFS2 was defined as the period from the start of first-line treatment after castration resistance to progression on second-line treatment. To minimize selection bias from possible confounders, we performed propensity score matching using one-to-one nearest neighbor matching without replacement.
Overall, 106 and 209 patients were administered the AA sequential therapy and DTX-combined sequential therapy, respectively. The clinicopathological variables of patients were well balanced after propensity score matching, and there were no significant differences between the two groups. In the propensity score-matched cohort, OS was not significantly different between the two groups (median, 37.9 vs. 45.4 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.68-1.79; p = .701), while PFS2 was significantly shorter in the AA group than in the DTX-combined group (median, 12.9 vs. 21.6 months; HR, 1.70; 95% CI, 1.16-2.48; p = .007).
Certain patients with CRPC can benefit from ART-to-ART sequential therapy in a daily clinical setting.
对于去势抵抗性前列腺癌（CRPC），最佳的序贯治疗方案仍不明确。近年来，人们对 CRPC 患者接受雄激素受体轴靶向药物（如阿比特龙（ABI）或恩扎卢胺（ENZ））序贯治疗的临床获益产生了一些质疑。我们比较了 CRPC 患者接受雄激素受体轴靶向药物序贯治疗（ART 序贯治疗）与多西他赛（DTX）联合序贯治疗（ART 转 DTX 或 DTX 转 ART）的效果。
我们回顾性地分析了 2009 年至 2019 年在我们 7 家附属医院接受治疗的 315 例 CRPC 患者的数据。所有患者在去势抵抗后均接受 DTX 或 ART（ABI 或 ENZ）作为一线或二线治疗。我们比较了去势抵抗后开始一线治疗后的总生存期（OS）和二线治疗后的第二次无进展生存期（PFS2），其中 PFS2 定义为从去势抵抗后的一线治疗开始到二线治疗进展的时间段。为了尽量减少可能的混杂因素造成的选择偏倚，我们采用了无替换的一对一最近邻匹配的倾向评分匹配。
总体而言，106 例患者接受了 ART 序贯治疗，209 例患者接受了 DTX 联合序贯治疗。经过倾向评分匹配后，患者的临床病理变量得到很好的平衡，两组间无显著差异。在倾向评分匹配队列中，两组间 OS 无显著差异（中位 OS，37.9 个月 vs. 45.4 个月；风险比 [HR]，1.10；95%置信区间 [CI]，0.68-1.79；p = .701），而 ART 序贯组的 PFS2 明显短于 DTX 联合序贯组（中位 PFS2，12.9 个月 vs. 21.6 个月；HR，1.70；95%CI，1.16-2.48；p = .007）。
在日常临床实践中，某些 CRPC 患者可以从 ART 序贯治疗中获益。
