Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy.
Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy.
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DOI：
10.1056/nejmoa1702900
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发表时间：
2017-07-27
期刊：
影响因子：
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通讯作者：
STAMPEDE Investigators
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作者：
James ND;de Bono JS;Spears MR;Clarke NW;Mason MD;Dearnaley DP;Ritchie AWS;Amos CL;Gilson C;Jones RJ;Matheson D;Millman R;Attard G;Chowdhury S;Cross WR;Gillessen S;Parker CC;Russell JM;Berthold DR;Brawley C;Adab F;Aung S;Birtle AJ;Bowen J;Brock S;Chakraborti P;Ferguson C;Gale J;Gray E;Hingorani M;Hoskin PJ;Lester JF;Malik ZI;McKinna F;McPhail N;Money-Kyrle J;O'Sullivan J;Parikh O;Protheroe A;Robinson A;Srihari NN;Thomas C;Wagstaff J;Wylie J;Zarkar A;Parmar MKB;Sydes MR;STAMPEDE Investigators
醋酸阿比特龙联合泼尼松龙可提高复发性前列腺癌患者的生存率我们采用多组、多阶段试验设计，评估了这种联合治疗对开始长期雄激素剥夺治疗（ADT）的男性的影响。我们以1：1的比例将患者随机分配接受ADT单药治疗或ADT+醋酸阿比特龙（每日1000 mg）和泼尼松龙（每日5 mg）（联合治疗）。局部放射治疗是强制性的，对于淋巴结阴性，非转移性疾病的患者，并鼓励那些积极的节点。对于未计划放疗的非转移性疾病患者和转移性疾病患者，治疗持续至放射学、临床或前列腺特异性抗原（PSA）进展;否则，治疗持续2年或直至任何类型的进展，以先发生者为准。主要结果指标是总生存率。中间主要结局是无失败生存期（治疗失败定义为放射学、临床或PSA进展或前列腺癌死亡）。从2011年11月至2014年1月，共有1917例患者接受了随机化。中位年龄为67岁，中位PSA水平为53 ng/ml。共有52%的患者患有转移性疾病，20%患有淋巴结阳性或淋巴结不确定的非转移性疾病，28%患有淋巴结阴性的非转移性疾病; 95%患有新诊断的疾病。中位随访时间为40个月。联合用药组有184例死亡，而ADT单药组有262例死亡（风险比为0.63; 95%可信区间[CI]为0.52 ~ 0.76; P<0.001）;非转移性疾病患者的风险比为0.75，转移性疾病患者的风险比为0.61。联合用药组有248例治疗失败事件，而ADT单药组有535例（风险比，0.29; 95%CI，0.25 - 0.34; P<0.001）;非转移性疾病患者的风险比为0.21，转移性疾病患者的风险比为0.31。联合用药组47%的患者发生3 - 5级不良事件（9起5级事件），ADT单药组33%的患者发生3 - 5级不良事件（3起5级事件）。在局部晚期或转移性前列腺癌男性患者中，ADT联合阿比特龙和泼尼松龙与ADT单药相比，总体和无失败生存率显著更高。（由英国癌症研究所资助）和其他; STAMPEDE ClinicalTrials.gov编号，NCT 00268476和当前对照试验编号，ISRCTN 78818544。）
Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design. We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy). Local radiotherapy was mandated for patients with node-negative, nonmetastatic disease and encouraged for those with positive nodes. For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease, treatment continued until radiologic, clinical, or prostate-specific antigen (PSA) progression; otherwise, treatment was to continue for 2 years or until any type of progression, whichever came first. The primary outcome measure was overall survival. The intermediate primary outcome was failure-free survival (treatment failure was defined as radiologic, clinical, or PSA progression or death from prostate cancer). A total of 1917 patients underwent randomization from November 2011 through January 2014. The median age was 67 years, and the median PSA level was 53 ng per milliliter. A total of 52% of the patients had metastatic disease, 20% had node-positive or node-indeterminate nonmetastatic disease, and 28% had node-negative, nonmetastatic disease; 95% had newly diagnosed disease. The median follow-up was 40 months. There were 184 deaths in the combination group as compared with 262 in the ADT-alone group (hazard ratio, 0.63; 95% confidence interval [CI], 0.52 to 0.76; P<0.001); the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease. There were 248 treatment-failure events in the combination group as compared with 535 in the ADT-alone group (hazard ratio, 0.29; 95% CI, 0.25 to 0.34; P<0.001); the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease. Grade 3 to 5 adverse events occurred in 47% of the patients in the combination group (with nine grade 5 events) and in 33% of the patients in the ADT-alone group (with three grade 5 events). Among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. (Funded by Cancer Research U.K. and others; STAMPEDE ClinicalTrials.gov number, NCT00268476, and Current Controlled Trials number, ISRCTN78818544.)