Maughan Benjamin L, Luber Brandon, Nadal Rosa, Antonarakis Emmanuel S
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Prostate. 2017 Jan;77(1):33-40. doi: 10.1002/pros.23246. Epub 2016 Aug 16.
There are no validated clinical decision tools to aid optimal treatment selection in men with metastatic castration-resistant prostate cancer (mCRPC). Frequently, abiraterone and enzalutamide are used prior to chemotherapy in mCRPC, given the more favorable safety profiles. However, there is no published data on clinical outcomes regarding best sequencing of these two agents.
A retrospective analysis of consecutive mCRPC patients treated with enzalutamide and abiraterone at Johns Hopkins was conducted. Patients were treated with sequential enzalutamide and abiraterone, in either order. The combined progression-free survival (PFS: PFS1 + PFS2) of abiraterone-to-enzalutamide was compared to the reverse sequence, where PFS1 and PFS2 represented clinical/radiographic progression-free survival on the first and second agents, respectively. Overall survival (OS) from the start of the first therapy to death and PSA response rates (defined as ≥50% PSA declines at any time) were also compared between groups. Outcomes were adjusted using propensity score-weighted multivariable Cox analyses.
Eighty-one patients who satisfied our entry criteria were identified: 65 in the abiraterone-to-enzalutamide group and 16 in the enzalutamide-to-abiraterone group. There were no significant baseline differences between groups. Multivariable analysis suggested a difference between groups favoring the abiraterone-to-enzalutamide sequence with respect to combined PFS (HR 0.37, 95%CI 0.22-0.64, P < 0.001). There was no statistical difference in OS between the groups after multivariable adjustment (HR 0.57, 95%CI 0.29-1.11, P = 0.098), although OS was numerically superior in the abiraterone-to-enzalutamide group.
We observed differences suggesting improved outcomes favoring the abiraterone-to-enzalutamide sequence in men with mCRPC, with statistical confirmation in terms of PFS but not OS. Prospective studies are required to verify these hypothesis-generating findings. Further evaluation of biomarkers to inform optimal treatment sequencing in men with mCRPC is urgently needed. Prostate 77:33-40, 2017. © 2016 Wiley Periodicals, Inc.
目前尚无经过验证的临床决策工具来辅助转移性去势抵抗性前列腺癌（mCRPC）患者进行最佳治疗选择。鉴于阿比特龙和恩杂鲁胺具有更良好的安全性，在mCRPC患者中，化疗前常使用这两种药物。然而，关于这两种药物最佳用药顺序的临床结局尚无公开数据。
对约翰霍普金斯医院接受恩杂鲁胺和阿比特龙治疗的连续性mCRPC患者进行回顾性分析。患者按顺序接受恩杂鲁胺和阿比特龙治疗，顺序不限。比较阿比特龙序贯恩杂鲁胺与相反顺序的联合无进展生存期（PFS：PFS1 + PFS2），其中PFS1和PFS2分别代表第一种和第二种药物治疗时的临床/影像学无进展生存期。还比较了两组从首次治疗开始至死亡的总生存期（OS）和PSA缓解率（定义为任何时间PSA下降≥50%）。使用倾向评分加权多变量Cox分析对结局进行调整。
确定了81名符合纳入标准的患者：阿比特龙序贯恩杂鲁胺组65例，恩杂鲁胺序贯阿比特龙组16例。两组之间基线无显著差异。多变量分析表明，联合PFS方面，两组存在差异，阿比特龙序贯恩杂鲁胺顺序更优（HR 0.37，95%CI 0.22 - 0.64，P < 0.001）。多变量调整后，两组OS无统计学差异（HR 0.57，95%CI 0.29 - 1.11，P = 0.098），尽管阿比特龙序贯恩杂鲁胺组的OS在数值上更优。
我们观察到mCRPC男性患者中，阿比特龙序贯恩杂鲁胺顺序的结局有所改善，在PFS方面有统计学证实，但OS无统计学证实。需要进行前瞻性研究来验证这些产生假设的发现。迫切需要进一步评估生物标志物，以为mCRPC男性患者的最佳治疗顺序提供依据。《前列腺》77:33 - 40，2017。© 2016威利期刊公司
