新型雄激素受体抑制剂（ARIs；达洛鲁胺、恩杂鲁胺和阿帕鲁胺）是非转移性去势抵抗性前列腺癌 (nmCRPC) 的标准治疗方法。然而，比较它们的临床使用和耐受性的数据很少。为了比较 nmCRPC 患者中达洛鲁胺、恩杂鲁胺和阿帕鲁胺的临床使用和结果。这项回顾性队列研究回顾了来自美国泌尿外科实践 Precision Point Specialty 网络的电子病历。符合条件的患者患有 nmCRPC，既往未接受过新型激素治疗，并在 2019 年 8 月 1 日至 2022 年 3 月 31 日期间开始新型 ARI 治疗。数据分析时间为 2019 年 2 月 1 日至 2022 年 12 月 31 日。患者接受了达洛鲁胺、恩杂鲁胺或apalutamide 是他们的首个治疗 nmCRPC 的新型 ARI。主要结局是 2 个终点的复合，即治疗终止和进展为转移性 CRPC (mCRPC)，以先发生者为准。两个终点也分别进行了评估。纳入了所有 870 名符合资格标准的患者（362 名患者接受达洛鲁胺治疗 [41.6%]；382 名患者接受恩杂鲁胺治疗[43.9%]；126 名患者接受阿帕鲁胺治疗[14.5%]）；平均 (SD) 年龄为 78.8 (8.7) 岁。 187 名患者 (21.5%) 自我报告的种族为黑人或非裔美国人，585 名患者 (67.2%) 为白人，98 名患者 (11.3%) 为其他种族或未知种族。达洛鲁胺队列中发生复合终点事件的患者比例较低（恩杂鲁胺为 134 例 [37.0%]，恩杂鲁胺为 201 例 [52.6%]，阿帕鲁胺为 66 例 [52.4%]），停药患者比例较低（达洛鲁胺为 110 例 [30.4%]，恩杂鲁胺为 156 例）。研究期间，恩杂鲁胺为 40.8%]，阿帕鲁胺为 58 [46.0%]，进展为 mCRPC（达洛鲁胺为 64 [17.7%]，恩杂鲁胺为 108 [28.3%]，阿帕鲁胺为 35 [27.8%]）。调整基线协变量后，与恩杂鲁胺（风险降低，33.8%；风险比 [HR]， 0.66 [95% CI，0.53-0.84]）和阿帕鲁胺（风险降低）相比，接受达洛鲁胺治疗的患者发生复合终点事件的风险较低降低，35.1%；HR，0.65 [95% CI，0.48-0.88]）。同样，与恩杂鲁胺（风险降低，27.4%；HR，0.73 [95% CI，0.56-0.94]）和阿帕鲁胺（风险降低，39.1%；HR，0.61 [95% CI，0.56-0.94]）相比，接受达洛鲁胺治疗的患者停药的风险较低，0.44-0.85]），与恩杂鲁胺（风险降低，40.6%；HR，0.59 [95% CI，0.43-0.82]）和阿帕鲁胺（风险降低，35.3%；HR，0.65）相比，进展为 mCRPC 的风险更低[ 95% CI，0.42-0.99]）。恩杂鲁胺和阿帕鲁胺治疗的结局没有差异。在这项对接受新型 ARI 治疗的 nmCRPC 患者进行的大型队列研究中，结果表明，与恩杂鲁胺和阿帕鲁胺相比，达洛鲁胺具有更好的耐受性，这可能与临床疗效优势相关。在缺乏头对头临床试验的情况下，需要进行比较临床研究来指导治疗决策。

Novel androgen receptor inhibitors (ARIs; darolutamide, enzalutamide, and apalutamide) are standard-of-care treatments for nonmetastatic castration-resistant prostate cancer (nmCRPC). However, there are sparse data comparing their clinical use and tolerability.To compare clinical use and outcomes for darolutamide, enzalutamide, and apalutamide in patients with nmCRPC.This retrospective cohort study reviewed electronic medical records from the Precision Point Specialty network of US urology practices. Eligible patients had nmCRPC and no prior novel hormonal therapy and initiated novel ARI treatment between August 1, 2019, and March 31, 2022. Data were analyzed from February 1, 2019, to December 31, 2022.Patients were prescribed darolutamide, enzalutamide, or apalutamide as their first novel ARI for nmCRPC.The main outcome was a composite of 2 end points, treatment discontinuation and progression to metastatic CRPC (mCRPC), whichever occurred first. Both end points were also assessed separately.All 870 patients meeting eligibility criteria were included (362 receiving darolutamide [41.6%]; 382, enzalutamide [43.9%]; 126, apalutamide [14.5%]); mean (SD) age was 78.8 (8.7) years. Self-reported race was Black or African American in 187 patients (21.5%), White in 585 (67.2%), and other or unknown in 98 (11.3%). The darolutamide cohort had lower proportions of patients with a composite end point event (134 [37.0%] vs 201 [52.6%] for enzalutamide and 66 [52.4%] for apalutamide), discontinuation (110 [30.4%] for darolutamide vs 156 [40.8%] for enzalutamide and 58 [46.0%] for apalutamide), and progression to mCRPC (64 [17.7%] for darolutamide vs 108 [28.3%] for enzalutamide and 35 [27.8%] for apalutamide) during the study period. After adjusting for baseline covariates, patients receiving darolutamide had a lower risk of a composite end point event compared with enzalutamide (risk reduction, 33.8%; hazard ratio [HR], 0.66 [95% CI, 0.53-0.84]) and apalutamide (risk reduction, 35.1%; HR, 0.65 [95% CI, 0.48-0.88]). Similarly, patients receiving darolutamide had a lower risk of discontinuation compared with enzalutamide (risk reduction, 27.4%; HR, 0.73 [95% CI, 0.56-0.94]) and apalutamide (risk reduction, 39.1%; HR, 0.61 [95% CI, 0.44-0.85]) and a lower risk of progression to mCRPC compared with enzalutamide (risk reduction, 40.6%; HR, 0.59 [95% CI, 0.43-0.82]) and apalutamide (risk reduction, 35.3%; HR, 0.65 [95% CI, 0.42-0.99]). There was no difference between enzalutamide and apalutamide treatment across outcomes.In this large cohort study of patients with nmCRPC treated with novel ARIs, results suggest better tolerability for darolutamide compared with enzalutamide and apalutamide, which may be associated with a clinical effectiveness advantage. Comparative clinical studies are needed to guide treatment decisions in the absence of head-to-head clinical trials.