阿比特龙或恩扎鲁胺治疗转移性去势抵抗性前列腺癌患者的效果

阿比特龙酯和恩扎鲁胺被推荐作为转移性去势抵抗性前列腺癌（mCRPC）的优选治疗方案，但由于缺乏直接对比的临床试验，其相对疗效差异尚不明确。因此，亟需明确的指导方针以辅助做出知情的mCRPC治疗选择。本研究旨在比较使用阿比特龙酯或恩扎鲁胺治疗的mCRPC患者的临床结局。本为回顾性、多中心队列研究，包括在美国退伍军人事务部医疗系统中，于2014年1月1日至2022年10月30日间开始使用阿比特龙酯或恩扎鲁胺治疗的mCRPC患者。研究使用逆概率加权法（IPTW）平衡两组患者的基线特征，并评估不同时间点的限制平均生存时间（RMST）差异，包括总生存期（OS）、前列腺癌特异性生存期（PCS）、治疗转换或死亡时间（TTS）以及前列腺特异性抗原（PSA）反应时间（TTR）。共有5779例患者（中位年龄74.42岁，四分位数间距（IQR）为68.94-82.14岁）被纳入，随访中位时间为38至60个月。恩扎鲁胺组患者的OS较阿比特龙组更长，4年时的RMST分别为24.29个月（95% CI，23.58-24.99月）和23.38个月（95% CI，22.85-23.92月），差异为0.90个月（95% CI，0.02-1.79月）。类似地，恩扎鲁胺组在TTS和TTR方面也表现出改善，4年时的RMST分别延长1.95个月（95% CI，0.92-2.99月）和缩短3.57个月（95% CI，1.76-5.38月）。在PCS方面，2年时的RMST延长0.48个月（95% CI，0.01-0.95月）。亚组分析显示，在未接受多西他赛治疗的患者以及PSA倍增时间≥3个月的患者中，恩扎鲁胺的起始与OS的RMST延长相关（分别为1.14个月，95% CI，0.19-2.10个月；以及2.23个月，95% CI，0.81-3.66个月），而在接受多西他赛治疗的患者或PSA倍增时间<3个月的患者中未观察到此关联（分别为-0.25个月，95% CI，-2.59至2.09个月；以及0.05个月，95% CI，-1.05至1.15个月）。在这项关于mCRPC患者的队列研究中，恩扎鲁胺的起始比阿比特龙酯在OS、PCS、TTS和TTR方面均有微小但统计学上显著的改善，尤其是在短期结局如TTS和TTR以及未接受多西他赛或PSA倍增时间较长的亚组中更为明显。

Abiraterone acetate and enzalutamide are recommended as preferred treatments for metastatic castration-resistant prostate cancer (mCRPC), but differences in their relative efficacy are unclear due to a lack of head-to-head clinical trials. Clear guidance is needed for making informed mCRPC therapeutic choices.To compare clinical outcomes in patients with mCRPC treated with abiraterone acetate or enzalutamide.This retrospective, multicenter cohort study included patients with mCRPC in the US Department of Veterans Affairs health care system who initiated treatment with abiraterone acetate or enzalutamide between January 1, 2014, and October 30, 2022.Abiraterone acetate or enzalutamide.The study used inverse probability of treatment weighting to balance baseline characteristics between patients initiating abiraterone acetate or enzalutamide and evaluated restricted mean survival time (RMST) differences in overall survival (OS), prostate cancer-specific survival (PCS), time to next treatment switching or death (TTS), and time to prostate-specific antigen (PSA) response (TTR) at different time points after treatment initiation.The study included 5779 patients (median age, 74.42 years [IQR, 68.94-82.14 years]). Median follow-up was between 38 and 60 months. Patients initiating enzalutamide on average had longer OS than those initiating abiraterone acetate, with RMSTs of 24.29 months (95% CI, 23.58-24.99 months) and 23.38 months (95% CI, 22.85-23.92 months), respectively, and a difference in RMST of 0.90 months (95% CI, 0.02-1.79 months) at 4 years. Similarly, TTS and TTR were improved in patients initiating enzalutamide, with an RMST at 4 years of 1.95 months (95% CI, 0.92-2.99 months) longer for TTS and 3.57 months (95% CI, 1.76-5.38 months) shorter for TTR. For PCS, the RMST at 2 years was 0.48 months (95% CI, 0.01-0.95 months) longer. An examination of subgroups identified that enzalutamide initiation was associated with longer RMST in OS among patients without prior docetaxel treatment (1.14 months; 95% CI, 0.19-2.10 months) and in those with PSA doubling time of 3 months or longer (2.23 months; 95% CI, 0.81-3.66 months) but not among patients with prior docetaxel (-0.25 months; 95% CI, -2.59 to 2.09 months) or with PSA doubling time of less than 3 months (0.05 months; 95% CI, -1.05 to 1.15 months).In this cohort study of patients with mCRPC, initiation of enzalutamide was associated with small but statistically significant improvements in OS, PCS, TTS, and TTR compared with initiation of abiraterone acetate. The improvements were more prominent in short-term outcomes, including TTS and TTR, and in patient subgroups without prior docetaxel or with PSA doubling time longer than 3 months.