Siemens D Robert, Klotz Laurence, Heidenreich Axel, Chowdhury Simon, Villers Arnauld, Baron Benoit, van Os Steve, Hasabou Nahla, Wang Fong, Lin Ping, Shore Neal D
Centre for Applied Urological Research, Queen's University, Kingston, Ontario, Canada.
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
J Urol. 2018 Jan;199(1):147-154. doi: 10.1016/j.juro.2017.08.080. Epub 2017 Aug 19.
Enzalutamide significantly prolonged median progression-free survival vs bicalutamide in chemotherapy naïve men with metastatic castration resistant prostate cancer in the TERRAIN (Enzalutamide versus Bicalutamide in Castrate Men with Metastatic Prostate Cancer) trial. In this post hoc analysis we investigated the influence of age on the efficacy and safety of enzalutamide vs bicalutamide in this population.
Patients were randomized 1:1 to enzalutamide 160 mg per day or bicalutamide 50 mg per day. Progression-free survival, time to prostate specific antigen progression and safety were analyzed post hoc in younger (age less than 75 years) and older (age 75 years or greater) subgroups.
Enzalutamide significantly reduced the risk of disease progression or death vs bicalutamide in patients younger than 75 years (HR 0.38, 95% CI 0.27-0.52, p <0.0001) and 75 years old or older (HR 0.59, 95% CI 0.37-0.92, p = 0.018). Time to prostate specific antigen progression was also significantly prolonged with enzalutamide vs bicalutamide in each subgroup. The adverse event distribution between treatments was similar in each subgroup except for more (5% or greater difference between subgroups) atrial fibrillation, urinary tract infections, falls and decreased appetite as well as less extremity pain and hot flushing in enzalutamide treated patients 75 years old or older, and less back pain and hot flushing in bicalutamide treated patients 75 years old or older. Grade 3 or greater cardiac events were more frequent in enzalutamide treated and bicalutamide treated patients who were 75 years old or older vs younger than 75 years. Fatigue was more frequent in enzalutamide treated patients with a similar distribution in each age subgroup.
Enzalutamide improved clinical outcomes vs bicalutamide irrespective of age. Increased falls and cardiac events suggest caution when prescribing to older patients (age 75 years or greater) with significant comorbidity.
在TERRAIN（转移性去势抵抗性前列腺癌去势男性中恩杂鲁胺对比比卡鲁胺）试验中，与比卡鲁胺相比，恩杂鲁胺显著延长了未接受过化疗的转移性去势抵抗性前列腺癌男性患者的中位无进展生存期。在这项事后分析中，我们研究了年龄对该人群中恩杂鲁胺对比比卡鲁胺疗效和安全性的影响。
患者按1:1随机分组，分别接受每日160毫克恩杂鲁胺或每日50毫克比卡鲁胺治疗。对年龄较轻（小于75岁）和年龄较大（75岁及以上）亚组进行事后分析，评估无进展生存期、前列腺特异性抗原进展时间和安全性。
在年龄小于75岁（风险比[HR] 0.38，95%置信区间[CI] 0.27 - 0.52，p <0.0001）和75岁及以上（HR 0.59，95% CI 0.37 - 0.92，p = 0.018）的患者中，与比卡鲁胺相比，恩杂鲁胺显著降低了疾病进展或死亡风险。在每个亚组中，恩杂鲁胺对比比卡鲁胺也显著延长了前列腺特异性抗原进展时间。各亚组中，除75岁及以上接受恩杂鲁胺治疗的患者房颤、尿路感染、跌倒和食欲下降更多（亚组间差异5%或更大），肢体疼痛和潮热更少，以及75岁及以上接受比卡鲁胺治疗的患者背痛和潮热更少外，各治疗组之间的不良事件分布相似。75岁及以上接受恩杂鲁胺和比卡鲁胺治疗的患者3级或更高级别的心脏事件比75岁以下患者更频繁。恩杂鲁胺治疗的患者疲劳更常见，且在各年龄亚组中分布相似。
无论年龄如何，恩杂鲁胺对比比卡鲁胺均改善了临床结局。跌倒和心脏事件增加提示，为合并症严重的老年患者（75岁及以上）开处方时需谨慎。
