Bilen Mehmet A, Lowentritt Benjamin, Khilfeh Ibrahim, Rossi Carmine, Du Shawn, Kinkead Frederic, Diaz Lilian, Pilon Dominic, Ellis Lorie, Shore Neal D
Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Chesapeake Urology, Towson, MD, USA.
Adv Ther. 2025 May 29. doi: 10.1007/s12325-025-03207-6.
Survival outcomes associated with different androgen receptor pathway inhibitors (ARPIs) prescribed for the treatment of metastatic castration (hormone)-sensitive prostate cancer (mCSPC) have not been directly compared. The objective of this study was to compare overall survival (OS) by 24 months among ARPI-naïve patients with mCSPC initiating apalutamide or enzalutamide.
A retrospective, causal longitudinal inverse probability of treatment weighted analysis was conducted to compare OS between patients initiating apalutamide or enzalutamide between December 2019 and December 2023 using de-identified linked US clinical and insurance claims data. Patients were excluded if they had prior exposure to ARPIs, had evidence of castration resistance, had < 12 months of database activity prior to ARPI initiation, were diagnosed with other primary cancers, or were treated with other advanced prostate cancer (PC)-related treatment (except docetaxel). Using an intention-to-treat approach, weighted Cox proportional hazards models were used to compare OS by 24 months between patients treated with apalutamide or enzalutamide (primary analyses; exploratory analyses used all available follow-up).
Overall, 1810 and 1909 ARPI-naïve patients who initiated apalutamide or enzalutamide, respectively, were included. Measured baseline characteristics between cohorts were well balanced after weighting (for both: mean age 73.0 years, ~ 60% white, ~ 23% black or African American, ~ 78% Medicare-insured, mean Quan-CCI 8.6, ~ 20% with visceral metastasis, 56.2% with de novo PC). At 24 months post index, there was a statistically significant 23% reduction in the risk of mortality among patients who initiated apalutamide compared with enzalutamide (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.62, 0.96; p = 0.019). Results remained consistent when using all available follow-up metrics (HR 0.77; 95% CI 0.64, 0.93; nominal p = 0.008).
In this head-to-head causal analysis among ARPI-naïve patients with mCSPC, treatment with apalutamide resulted in better survival outcomes at 24 months compared with enzalutamide. Longer follow-up studies are required to fully determine the therapeutic comparator impact of these agents.
用于治疗转移性去势（激素）敏感性前列腺癌（mCSPC）的不同雄激素受体通路抑制剂（ARPI）相关的生存结果尚未得到直接比较。本研究的目的是比较初治mCSPC且开始使用阿帕他胺或恩杂鲁胺的患者24个月时的总生存期（OS）。
采用回顾性、因果纵向逆概率治疗加权分析，使用去识别化的美国临床与保险理赔关联数据，比较2019年12月至2023年12月开始使用阿帕他胺或恩杂鲁胺的患者的OS。如果患者曾接触过ARPI、有去势抵抗证据、在开始使用ARPI前数据库活动时间不足12个月、被诊断患有其他原发性癌症或接受过其他晚期前列腺癌（PC）相关治疗（多西他赛除外），则将其排除。采用意向性治疗方法，使用加权Cox比例风险模型比较使用阿帕他胺或恩杂鲁胺治疗的患者24个月时的OS（主要分析；探索性分析使用所有可用的随访数据）。
总体而言，分别纳入了1810例和1909例初治且开始使用阿帕他胺或恩杂鲁胺的患者。加权后各队列间测量的基线特征均衡良好（两者均为：平均年龄73.0岁，约60%为白人，约23%为黑人或非裔美国人，约78%有医疗保险，平均全人群合并症指数8.6，约20%有内脏转移，56.2%为新发PC）。在索引后24个月时，与恩杂鲁胺相比，开始使用阿帕他胺的患者死亡风险有统计学意义地降低了23%（风险比[HR]0.77；95%置信区间[CI]0.62，0.96；p = 0.019）。使用所有可用的随访指标时结果仍然一致（HR 0.77；95% CI 0.64，0.93；名义p = 0.008）。
在这项初治mCSPC患者的直接因果分析中，与恩杂鲁胺相比，使用阿帕他胺治疗在24个月时可带来更好的生存结果。需要更长时间的随访研究来全面确定这些药物的治疗比较效果。
