Department of Urology, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Cancer Treat Rev. 2022 Nov;110:102441. doi: 10.1016/j.ctrv.2022.102441. Epub 2022 Jul 26.
The current standard of care for the systemic treatment of metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) with either docetaxel or advanced androgen blockage (AAB). Recently, two studies have tested the combination of ADT, docetaxel and AAB (triplet therapy) relative to docetaxel and ADT in this setting. Herein, we aimed to compare the effect on survival outcomes of available systemic treatments for mHSPC.
A comprehensive search for all published phase III randomized control trials on first line mHSPC that evaluated AAB (TITAN, ARCHES, STAMPEDE, LATITUDE, ENZAMET) or docetaxel (GETUG-AFU15, CHAARTED, STAMPEDE) or their combination (ARASENS, PEACE-1) was conducted PubMed, EMBASE, Web of Science, and Scopus databases up to 15/04/2022. We reconstructed survival data from published Kaplan-Meier curves on overall survival (OS) and progression free survival (PFS) and meta-analyzed docetaxel versus AAB versus triplet therapy (grouping together abiraterone/darolutamide and docetaxel). The outcomes of interest were assessed using differences in restricted mean survival time (ΔRMST) at different time points and Cox regression.
Ten trials were included involving 5,544 patients for assessing OS and 5,725 for PFS. Triplet therapy was associated with longer OS when compared to docetaxel (48-month ΔRMST: 2.6; 95 %CI: 1.8,3.4; p < 0.001) but yielded similar OS when compared to AAB (48-month ΔRMST: -0.8; 95 % CI: -1.8, 0.2; p = 0.1). Similarly, triplet therapy was associated with longer PFS when compared to docetaxel (48-month ΔRMST: 10.3; 95 %CI: 9.0,11.6; p < 0.001) but yielded similar PFS when compared to AAB (48-month ΔRMST: 1.1; 95 %CI: -0.2,2.3; p = 0.1).
Overall, we found no OS nor PFS benefit for patients with mHSPC treated with triplet therapy compared to AAB alone, while an advantage emerged for both AAB or triplet therapy relative to docetaxel.
转移性去势敏感型前列腺癌（mHSPC）的系统治疗目前的标准治疗包括雄激素剥夺治疗（ADT）联合多西他赛或高级别雄激素阻断（AAB）。最近，两项研究比较了 ADT、多西他赛和 AAB（三联疗法）与该治疗环境中的多西他赛联合 ADT 的疗效。在此，我们旨在比较 mHSPC 可用的系统治疗方法对生存结果的影响。
我们对所有已发表的一线 mHSPC 中评估 AAB（TITAN、ARCHES、STAMPEDE、LATITUDE、ENZAMET）或多西他赛（GETUG-AFU15、CHAARTED、STAMPEDE）或其联合治疗（ARASENS、PEACE-1）的 III 期随机对照试验进行了全面检索。我们使用 PubMed、EMBASE、Web of Science 和 Scopus 数据库进行了检索，检索时间截至 2022 年 4 月 15 日。我们从已发表的总生存期（OS）和无进展生存期（PFS）的 Kaplan-Meier 曲线中重建了生存数据，并对多西他赛与 AAB 与三联疗法（将阿比特龙/达罗他胺和多西他赛组合在一起）进行了荟萃分析。使用不同时间点的限制性平均生存时间（ΔRMST）和 Cox 回归评估了感兴趣的结局。
共纳入 10 项试验，涉及 5544 例患者评估 OS，5725 例患者评估 PFS。与多西他赛相比，三联疗法可延长 OS（48 个月 ΔRMST：2.6；95%CI：1.8，3.4；p<0.001），但与 AAB 相比，OS 无显著差异（48 个月 ΔRMST：-0.8；95%CI：-1.8，0.2；p=0.1）。同样，与多西他赛相比，三联疗法可延长 PFS（48 个月 ΔRMST：10.3；95%CI：9.0，11.6；p<0.001），但与 AAB 相比，PFS 无显著差异（48 个月 ΔRMST：1.1；95%CI：-0.2，2.3；p=0.1）。
总的来说，与单独使用 AAB 相比，我们未发现三联疗法治疗 mHSPC 患者在 OS 或 PFS 方面有获益，而 AAB 或三联疗法与多西他赛相比均有获益。
