Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment
Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment
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DOI：
10.1200/jco.2018.77.9827
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发表时间：
2018-09-01
影响因子：
45.3
通讯作者：
Taplin, Mary-Ellen
中科院分区：
文献类型：
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作者：
Attard, Gerhardt;Borre, Michael;Taplin, Mary-Ellen
目的恩扎鲁胺耐药可由雄激素升高引起，联合应用醋酸阿比特龙可克服其耐药性。柏拉图(ClinicalTrials.gov识别码：NCT01995513)使用随机、双盲、安慰剂对照设计对这一假设进行了询问。患者和方法在第一阶段，接受化疗的转移性去势抵抗前列腺癌的男性患者每天接受开放标签的苯扎鲁胺160 mg。在第13周和第21周，前列腺特异性抗原(PSA)没有升高的男性接受治疗，直到PSA进展(增加25%，低于最低点2 ng/ml)，然后在第二期按1：1比例随机分配给服用苯扎鲁胺或安慰剂的阿比特龙每天1,000毫克和泼尼松5毫克，每天两次(分别为联合组或对照组)，直到疾病进展(主要终点：无进展生存(研究期间放射学或明确的临床进展或死亡))。次要终点包括第二阶段的PSA进展时间和PSA反应。结果在第一阶段登记的509名患者中，251人被随机分配到第二阶段。中位无进展生存期联合组为5.7个月，对照组为5.6个月(风险比，0.83；95%CI，0.61至1.12；P=.22)。次要终点无差异。联合用药组3级高血压(10%比2%)和ALT升高(6%比2%)或AST升高(2%比0%)发生率更高。结论苯扎鲁胺与醋酸阿比特龙和强的松联合治疗PSA进展后不宜联合应用苯扎鲁胺，合并高血压和肝酶升高的发生率较高。
PurposeEnzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO (ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design.Patients and MethodsIn period one, men with chemotherapy-naive metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression ( 25% increase and 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two.ResultsOf 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group.ConclusionCombining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy.