Uemura Hiroji, Satoh Takefumi, Tsumura Hideyasu, Arai Gaku, Imanaka Keiichiro, Shibayama Kazuhiro, Fujii Koji, Rooney Brendan, Lopez-Gitlitz Angela, Espina Byron, Perez-Ruixo Carlos, Small Eric J, Smith Matthew
Yokohama City University Medical Center, Yokohama, Japan.
Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Prostate Int. 2020 Dec;8(4):190-197. doi: 10.1016/j.prnil.2020.05.002. Epub 2020 May 28.
In the global Phase-3 Selective Prostate Androgen Receptor Targeting with ARN-509 study, apalutamide plus ongoing androgen deprivation therapy (ADT) significantly increased metastasis-free survival (MFS) and improved other clinical outcomes in men with nonmetastatic castration-resistant prostate cancer (nm-CRPC) who were at high risk of developing metastases. In this subpopulation analysis of Selective Prostate Androgen Receptor Targeting with ARN-509 study, the efficacy and safety of apalutamide plus ADT were evaluated in Japanese patients with nm-CRPC.
The primary efficacy end point was MFS. Secondary efficacy end points were time to metastasis, progression-free survival, symptomatic progression, initiation of cytotoxic chemotherapy, and overall survival. Safety and pharmacokinetic parameters were also assessed.
Fifty-five Japanese patients with ongoing ADT were randomized (apalutamide: n = 34, placebo: n = 21). Median treatment duration was 5.7 months in the apalutamide group and 11.0 months in the placebo group. Median MFS was not reached in the apalutamide group (95% confidence interval: 10.97, not estimable) and was 18.23 months (95% confidence interval: 11.04, 18.50) in the placebo group. Secondary end points were improved in the apalutamide group. The safety profile of apalutamide with ADT was comparable with the global population, and no new safety signals were identified in this Japanese subpopulation. Although, apalutamide exposure tended to be higher in the Japanese subpopulation compared with the non-Japanese population, this was likely to be explained by body weight and considered not clinically meaningful.
In the Japanese subpopulation, treatment with apalutamide with ADT resulted in favorable efficacy outcomes with comparable benefit-risk profile to the global population with nm-CRPC who are at high-risk of developing metastases.
在全球3期ARN-509选择性前列腺雄激素受体靶向治疗研究中，阿帕他胺联合持续雄激素剥夺治疗（ADT）显著提高了无转移生存期（MFS），并改善了有转移高风险的非转移性去势抵抗性前列腺癌（nm-CRPC）男性患者的其他临床结局。在这项ARN-509选择性前列腺雄激素受体靶向治疗研究的亚组分析中，评估了阿帕他胺联合ADT在日本nm-CRPC患者中的疗效和安全性。
主要疗效终点为MFS。次要疗效终点为转移时间、无进展生存期、症状进展、细胞毒性化疗开始时间和总生存期。还评估了安全性和药代动力学参数。
55例正在接受ADT的日本患者被随机分组（阿帕他胺组：n = 34，安慰剂组：n = 21）。阿帕他胺组的中位治疗持续时间为5.7个月，安慰剂组为11.0个月。阿帕他胺组未达到中位MFS（95%置信区间：10.97，不可估计），安慰剂组为18.23个月（95%置信区间：11.04，18.50）。阿帕他胺组的次要终点得到改善。阿帕他胺联合ADT的安全性与全球人群相当，在该日本亚组中未发现新的安全信号。尽管与非日本人群相比，日本亚组中阿帕他胺的暴露量往往更高，但这可能由体重来解释，且认为无临床意义。
在日本亚组中，阿帕他胺联合ADT治疗产生了良好的疗效结果，其获益风险特征与有转移高风险的全球nm-CRPC人群相当。
