Serum Androgens As Prognostic Biomarkers in Castration-Resistant Prostate Cancer: Results From an Analysis of a Randomized Phase III Trial
Serum Androgens As Prognostic Biomarkers in Castration-Resistant Prostate Cancer: Results From an Analysis of a Randomized Phase III Trial
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DOI：
10.1200/jco.2012.45.4595
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发表时间：
2013-08-01
影响因子：
45.3
通讯作者：
Scher, Howard I.
中科院分区：
文献类型：
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作者：
Ryan, Charles J.;Molina, Arturo;Scher, Howard I.
目的在III期研究COU-AA-301中，醋酸阿比特龙（AA）联合泼尼松（P）延长多西他赛治疗后转移性去势抵抗性前列腺癌（mCRPC）患者的总生存期（OS）。在这篇文章中，我们调查基线血清雄激素（SA）水平和OS.Patients和MethodsCOU-AA-301之间的关系是一个随机的，双盲研究AA（1,000毫克每天）加P（5毫克，每天两次，n = 797）与P单独（n = 398）。根据东部肿瘤协作组体力状态（0 - 1 v2）、疼痛（过去24小时简明疼痛量表-简表：4 - 10，存在; v 0 - 3，不存在）、既往化疗（1 v2）和进展（前列腺特异性抗原v放射学）对随机化进行分层。通过超灵敏液-液提取或蛋白沉淀和二维液相色谱-质谱联用测定基线SA（睾酮、雄烯二酮、硫酸脱氢表雄酮）与OS的相关性，通过双变量和多变量考克斯模型测定OS。OS检查SA大于中位数和小于或等于medium.ResultsMedian生存增加与睾酮水平的每个四分位数的增加，无论治疗arm. SA水平在基线强相关的生存（P < .0001）在双变量和多变量分析。在AA和P组中，SA高于中位数的患者的生存期长于SA低于中位数的患者（例如，睾酮，AA;风险比，0.64; 95%CI，0.53至0.77; P <0.0001）。AA治疗导致较长的生存期与P单独在上述或低于中位数组的所有androgens.ConclusionSA，一种新的超灵敏度测定COU-AA-301，测量OS的预后，并可能是有用的风险分层mCRPC临床试验。(C)2013年美国临床肿瘤学会
PurposeIn the phase III study COU-AA-301, abiraterone acetate (AA) plus prednisone (P) prolonged overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel administration. In this article, we investigate the relationship between baseline serum androgen (SA) levels and OS.Patients and MethodsCOU-AA-301 is a randomized, double-blind study of AA (1,000 mg every day) plus P (5 mg by mouth twice daily; n = 797) versus P alone (n = 398). Randomization was stratified by Eastern Cooperative Oncology Group performance status (0 to 1 v 2), pain (Brief Pain Inventory-Short Form over past 24 hours: 4 to 10, present; v 0 to 3, absent), prior chemotherapy (1 v 2), and progression (prostate-specific antigen v radiographic). Association of baseline SA (testosterone, androstenedione, dehydroepiandrosterone sulfate), was measured by ultrasensitive liquid-liquid extraction or protein precipitation and two-dimensional liquid chromatography coupled to mass spectrometry, with OS determined by bivariate and multivariable Cox models. OS was examined with SA as greater than median and less than or equal to the median.ResultsMedian survival increased with each quartile increase in testosterone level regardless of treatment arm. SA levels at baseline strongly associated with survival (P < .0001) in bivariate and multivariable analyses. Longer survival was observed for patients with SA above median compared with below median in both the AA and P arms (eg, testosterone, AA; hazard ratio, 0.64; 95% CI, 0.53 to 0.77; P < .0001). Treatment with AA led to longer survival versus P alone in the above-or below-median group for all androgens.ConclusionSA, measured with a novel ultrasensitive assay in COU-AA-301, is prognostic for OS and may be useful for risk stratification in mCRPC clinical trials. (C) 2013 by American Society of Clinical Oncology