Prior long response to androgen deprivation predicts response to next-generation androgen receptor axis targeted drugs in castration resistant prostate cancer
Prior long response to androgen deprivation predicts response to next-generation androgen receptor axis targeted drugs in castration resistant prostate cancer
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DOI：
10.1016/j.ejca.2015.06.128
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发表时间：
2015-09-01
影响因子：
8.4
通讯作者：
Fizazi, Karim
中科院分区：
文献类型：
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作者：
Loriot, Yohann;Eymard, Jean-Christophe;Fizazi, Karim
背景资料：对于去势抵抗性前列腺癌（CRPC）患者的治疗，迫切需要合格的敏感性预测生物标志物。我们试图确定准备使用的临床预测指标的改善结果在转移性CRPC（mCRPC）患者治疗下一代雄激素受体（AR）轴靶向drugs.Patients和方法：我们回顾了一个队列的患者接受AR轴靶向药物CRPC在两个主要的法国癌症中心。几个临床，生物学和放射学参数对无进展生存期（PFS）的预测作用进行了研究。对初始雄激素剥夺治疗（ADT）的中位反应持续时间（至去势抵抗的时间，TTCRPC）为17.8个月。在12个月以下和12个月以上的TTCRPC患者中，AR轴靶向药物的50%前列腺特异性抗原（PSA）应答率分别为16%（95%置信区间（CI）：6-27）和41%（95% CI：30-47）（p = 0.005）。中位PFS分别为2.8个月（95% CI：2.1-3.9）和5.8个月（95% CI：4.6-7.8; HR：0.58，p = 0.002）。根据TTCRPC，在多西他赛后Enzalutamide治疗患者（n = 57）中，中位PFS分别为2.8个月和8.6个月（风险比（HR）= 3.1; 95% CI：1.6-5.8，p = 0.0016），而在安慰剂治疗患者（n = 27）中未观察到差异。在TTCRPC小于和大于12个月的患者中，Enzalutamide的50%PSA缓解率分别为8%（95%CI：0-38）和58%（95%CI：42-73）（p < 0.001）。结论：既往ADT缓解持续时间是mCRPC患者对下一代AR轴靶向药物敏感性的预测因素。(C)2015由Elsevier Ltd.出版
Background: There is an urgent need for qualified predictive biomarkers of sensitivity for the treatments used in patients with castration-resistant prostate cancer (CRPC). We attempted to identify ready-to-use clinical predictors of improved outcome in metastatic CRPC (mCRPC) patients treated with next generation androgen receptor (AR) axis targeted drugs.Patients and methods: We reviewed a cohort of patients who received AR axis targeted drugs for CRPC at two major French cancer centres. The predictive role of several clinical, biological and radiological parameters on progression-free survival (PFS) was studied.Results: The study cohort consisted of 173 patients. Median duration of response to initial androgen deprivation therapy (ADT) (time to castration resistance, TTCRPC) was 17.8 months. The 50% prostate-specific antigen (PSA) response rate to AR axis targeted drugs was 16% (95% confidence interval (CI): 6-27) and 41% (95% CI: 30-47) in patients with TTCRPC of under and over 12 months respectively (p = 0.005). Median PFS was 2.8 months (95% CI: 2.1-3.9) and 5.8 (95% CI: 4.6-7.8; HR: 0.58, p = 0.002). In patients treated with post-docetaxel enzalutamide (n = 57), median PFS was 2.8 months and 8.6 months, (Hazard ratio (HR) = 3.1; 95% CI: 1.6-5.8, p = 0.0016) according to TTCRPC, whereas no difference was observed in placebo-treated patients (n = 27). The 50% PSA response rate to enzalutamide was 8% (95% CI: 0-38) and 58% (95% CI: 42-73) in patients with a TTCRPC of under and over 12 months respectively (p < 0.001).Conclusion: The previous duration of response to ADT is a predictor of sensitivity to next generation AR axis targeted drugs in patients with mCRPC. (C) 2015 Published by Elsevier Ltd.