Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC.
The University of Chicago, Chicago, IL.
J Clin Oncol. 2019 Nov 10;37(32):2974-2986. doi: 10.1200/JCO.19.00799. Epub 2019 Jul 22.
Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC).
ARCHES (ClinicalTrials.gov identifier: NCT02677896) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival.
As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; < .001; median not reached 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT ( < .001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events.
Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer.
恩扎卢胺是一种强效的雄激素受体抑制剂，已在转移性和非转移性去势抵抗性前列腺癌中显示出显著的益处。我们评估了恩扎卢胺在转移性激素敏感性前列腺癌（mHSPC）中的疗效和安全性。
ARCHES（临床试验编号：NCT02677896）是一项多中心、双盲、III 期试验，共纳入 1150 例 mHSPC 男性患者，按疾病体积和先前多西他赛化疗情况进行分层，以 1:1 的比例随机分配至恩扎卢胺（160mg/天）或安慰剂联合雄激素剥夺治疗（ADT）组。主要终点为影像学无进展生存期。
截至 2018 年 10 月 14 日，与安慰剂联合 ADT 相比，恩扎卢胺联合 ADT 可显著降低影像学进展或死亡风险（风险比，0.39；95%CI，0.30 至 0.50；<0.001；中位未达到 19.0 个月）。基于疾病体积和先前多西他赛治疗情况的预先设定亚组分析中，也观察到影像学无进展生存期的显著改善。恩扎卢胺联合 ADT 可显著降低前列腺特异性抗原进展、新抗肿瘤治疗开始、首次症状性骨骼事件、去势抵抗和疼痛进展风险。更多患者接受恩扎卢胺联合 ADT 治疗后达到了前列腺特异性抗原水平不可检测和/或客观缓解（<0.001）。两组患者治疗前的生活质量水平均较高，且随时间推移保持稳定。恩扎卢胺联合 ADT 组 24.3%的患者报告了 3 级或更高级别的不良事件，安慰剂联合 ADT 组为 25.6%，两组均未报告新的不良反应事件。
与安慰剂联合 ADT 相比，恩扎卢胺联合 ADT 可显著降低 mHSPC 患者的疾病转移进展或死亡风险，包括低体积疾病和/或先前接受过多西他赛治疗的患者，安全性分析似乎与恩扎卢胺在先前去势抵抗性前列腺癌临床试验中的安全性一致。
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