European Georges Pompidou Hospital, Paris, France.
Centre Armoricain d'Oncologie, CARIO, Plerin, France.
Eur Urol Oncol. 2018 Dec;1(6):467-475. doi: 10.1016/j.euo.2018.05.009. Epub 2018 Jun 8.
The optimal sequence of life-extending therapies in metastatic castration-resistant prostate cancer (mCRPC) is unknown.
To evaluate outcomes among mCRPC patients treated with docetaxel (DOC), cabazitaxel (CABA), and a novel androgen receptor-targeted agent (ART; abiraterone acetate or enzalutamide) according to three different sequences.
DESIGN, SETTING, AND PARTICIPANTS: Data from 669 consecutive mCRPC patients were retrospectively collected between November 2012 and October 2016.
The primary endpoint was the prostate-specific antigen (PSA) response (decrease ≥50% from baseline) to each therapy. Secondary endpoints included best clinical benefit, time to PSA progression, radiological progression-free survival (rPFS), overall survival (OS), and toxicity.
A total of 158 patients received DOC→CABA→ART (group 1), 456 received DOC→ART→CABA (group 2), and 55 received ART→DOC→CABA (group 3). At baseline, PSA progression only and Gleason <8 were more common in group 3. PSA response on DOC was lower in group 3 than in other groups (p=0.02) and PSA response on CABA was higher in the second than in the third line (p=0.001). In Group 3, rPFS on ART (6.6 mo) and DOC (9.2 mo) was also shorter than in the other groups. OS calculated from the first life-extending therapy reached 34.8, 35.8, and 28.9 mo in groups 1, 2 and 3, respectively (p=0.007). Toxicity was comparable between the arms. The main limitations of the trial are its retrospective design and the low number of patients in group 3.
In this retrospective trial, sequencing of DOC, CABA, and one ART, was associated with median OS of up to 35.8 mo. CABA seemed to retain its activity regardless of treatment sequence. DOC activity after ART appeared to be reduced, but the data are insufficient to conclude that cross-resistance occurs.
The order of drugs administered to patients with metastatic castration-resistant prostate cancer could impact their efficacy, with cabazitaxel appearing to retain its activity whatever the therapeutic sequence.
转移性去势抵抗性前列腺癌（mCRPC）中延长生命的治疗方法的最佳顺序尚不清楚。
根据三种不同的方案，评估接受多西他赛（DOC）、卡巴他赛（CABA）和新型雄激素受体靶向药物（ART；醋酸阿比特龙或恩扎卢胺）治疗的 mCRPC 患者的结局。
设计、地点和参与者：回顾性收集了 2012 年 11 月至 2016 年 10 月间 669 例连续 mCRPC 患者的数据。
主要终点是每种治疗方法的前列腺特异性抗原（PSA）应答（与基线相比下降≥50%）。次要终点包括最佳临床获益、PSA 进展时间、影像学无进展生存期（rPFS）、总生存期（OS）和毒性。
共有 158 例患者接受了 DOC→CABA→ART（第 1 组），456 例患者接受了 DOC→ART→CABA（第 2 组），55 例患者接受了 ART→DOC→CABA（第 3 组）。在基线时，第 3 组仅 PSA 进展和 Gleason<8 更常见。与其他组相比，第 3 组在 DOC 上的 PSA 反应较低（p=0.02），在 CABA 上的 PSA 反应在二线治疗中高于三线治疗（p=0.001）。在第 3 组中，ART（6.6 个月）和 DOC（9.2 个月）的 rPFS 也短于其他组。从第一次延长生命的治疗开始计算的 OS 在第 1、2 和第 3 组分别达到 34.8、35.8 和 28.9 个月（p=0.007）。各组之间的毒性相当。该试验的主要局限性在于其回顾性设计和第 3 组患者数量较少。
在这项回顾性试验中，DOC、CABA 和一种 ART 的治疗顺序与最长达 35.8 个月的中位 OS 相关。无论治疗顺序如何，CABA 似乎都保持其活性。在 ART 后，DOC 的活性似乎降低，但数据不足以得出发生交叉耐药的结论。
转移性去势抵抗性前列腺癌患者接受药物的顺序可能会影响其疗效，卡巴他赛无论治疗顺序如何，似乎都保持其活性。
