Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial
Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial
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DOI：
10.1016/s1470-2045(19)30688-6
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发表时间：
2019-12-01
期刊：
影响因子：
51.1
通讯作者：
Chi, Kim N.
中科院分区：
文献类型：
--
作者：
Khalaf, Daniel J.;Annala, Matti;Chi, Kim N.
背景醋酸阿比特龙加强的松和恩杂鲁胺都被用于治疗转移性去势抵抗性前列腺癌。我们的目的是确定使用这两种药物的最佳顺序，以及它们的二线疗效。在加拿大不列颠哥伦比亚省的6个癌症中心进行的这项多中心、随机、开放标签、2期交叉试验中，我们招募了年龄在18岁或以上的新诊断的转移性阉割抵抗性前列腺癌患者，这些患者没有神经内分泌分化，东部合作肿瘤组的表现状态为2或以下。使用计算机生成的随机数字表随机分配患者（1:1），接受醋酸阿比特龙1000 mg，每日口服一次，加强的松5 mg，每日口服两次，直到PSA进展，然后交叉到enzalutamide 160 mg，每日口服一次（a组），或相反的顺序（B组）。治疗没有对调查人员或参与者隐瞒。主要终点是二线治疗的PSA第二次进展时间和PSA反应（>=比基线下降30%），分别通过意向治疗对所有随机分配的患者和交叉患者进行分析。该试验已在ClinicalTrials.gov注册，注册号为NCT02125357。在2014年10月21日至2016年12月13日期间，202例患者入组，随机分为A组（n=101）和B组（n=101）。截止数据时，A组73例（72%）患者和B组75例（74%）患者发生交叉。A组到第二次PSA进展的时间比B组长（中位19.3个月[95% CI 16.0-30.5] vs 15.2个月[95% CI 11.9-19.8]个月；风险比0.66,95% CI 0.45-0.97, p=0.036），中位随访22.8个月（IQR 10.3-33.4）。73例恩杂鲁胺患者中有26例（36%）出现PSA应答，75例阿比特龙患者中有3例（4%）出现PSA应答
Background Abiraterone acetate plus prednisone and enzalutamide are both used for the treatment of metastatic castration-resistant prostate cancer. We aimed to determine the best sequence in which to use both drugs, as well as their second-line efficacy.Methods In this multicentre, randomised, open-label, phase 2, crossover trial done in six cancer centres in British Columbia, Canada, we recruited patients aged 18 years or older with newly-diagnosed metastatic castration-resistant prostate cancer without neuroendocrine differentiation and Eastern Cooperative Oncology Group performance status 2 or less. Patients were randomly assigned (1:1) using a computer-generated random number table to receive either abiraterone acetate 1000 mg orally once daily plus prednisone 5 mg orally twice daily until PSA progression followed by crossover to enzalutamide 160 mg orally once daily (group A), or the opposite sequence (group B). Treatment was not masked to investigators or participants. Primary endpoints were time to second PSA progression and PSA response (>= 30% decline from baseline) on second-line therapy, analysed by intention-to-treat in all randomly assigned patients and in patients who crossed over, respectively. The trial is registered with ClinicalTrials.gov, NCT02125357.Findings Between Oct 21, 2014, and Dec 13, 2016, 202 patients were enrolled and randomly assigned to either group A (n=101) or group B (n=101). At the time of data cutoff, 73 (72%) patients in group A and 75 (74%) patients in group B had crossed over. Time to second PSA progression was longer in group A than in group B (median 19.3 months [95% CI 16.0-30.5] vs 15.2 months [95% CI 11.9-19.8] months; hazard ratio 0.66, 95% CI 0.45-0.97, p=0.036), at a median follow-up of 22.8 months (IQR 10.3-33.4). PSA responses to second-line therapy were seen in 26 (36%) of 73 patients for enzalutamide and three (4%) of 75 for abiraterone (chi(2) p