Beer Tomasz M, George Daniel J, Shore Neal D, Winters-Stone Kerri, Wefel Jeffrey S, Verholen Frank, Srinivasan Shankar, Ortiz Jorge, Morgans Alicia K
Knight Cancer Institute, Oregon Health and Science University, Portland, OR 98239, United States.
Duke Cancer Institute, Duke University Shool of Medicine, Durham, NC, United States.
Oncologist. 2025 Jul 4;30(7). doi: 10.1093/oncolo/oyae287.
Androgen receptor inhibitors (ARIs) are approved for the treatment of advanced prostate cancer; however, some patients may experience symptoms and side effects that hinder their physical functioning. The Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) tests are used to assess physical functioning in older adults and are recommended assessments for patients with prostate cancer, despite lacking validation in this setting.
DaroAct (NCT04157088) was an open-label, multicenter, phase 2b study designed to evaluate the effects of the ARI darolutamide (lead-in phase) and darolutamide vs enzalutamide (randomized phase) on physical functioning in men with castration-resistant prostate cancer (CRPC). Only the lead-in phase, in which participants received darolutamide 600 mg twice daily, was completed. The TUG and SPPB tests were used to assess physical functioning.
The lead-in phase enrolled 30 participants. During 24 weeks of treatment, 8 (32.0%) of 25 evaluable participants exhibited clinically meaningful worsening in TUG from baseline (primary endpoint). At the week 24 visit, 5 (21.7%) of 23 participants had worsening in TUG time, and 8 (33.3%) of 24 participants had worsening in SPPB score. Because only 48% of participants had the same outcome on the TUG and SPPB tests, the study was terminated without initiating the randomized comparison.
Most participants showed no clinically meaningful worsening in physical functioning after 24 weeks of darolutamide treatment, but poor agreement between tests was observed. Tools to accurately and consistently measure the impact of ARIs on physical functioning in patients with CRPC are needed.
雄激素受体抑制剂（ARIs）已被批准用于治疗晚期前列腺癌；然而，一些患者可能会出现妨碍其身体功能的症状和副作用。定时起立行走测试（TUG）和简短体能测试电池（SPPB）用于评估老年人的身体功能，是前列腺癌患者推荐的评估方法，尽管在这种情况下缺乏验证。
DaroAct（NCT04157088）是一项开放标签、多中心、2b期研究，旨在评估ARI达罗他胺（导入期）以及达罗他胺与恩杂鲁胺对比（随机化期）对去势抵抗性前列腺癌（CRPC）男性患者身体功能的影响。仅完成了导入期，在此期间参与者每天两次服用600mg达罗他胺。使用TUG和SPPB测试评估身体功能。
导入期招募了30名参与者。在24周的治疗期间，25名可评估参与者中有8名（32.0%）的TUG从基线开始出现具有临床意义的恶化（主要终点）。在第24周就诊时，23名参与者中有5名（21.7%）的TUG时间恶化，24名参与者中有8名（33.3%）的SPPB评分恶化。由于只有48%的参与者在TUG和SPPB测试中结果相同，因此未启动随机比较就终止了该研究。
大多数参与者在接受24周达罗他胺治疗后身体功能没有出现具有临床意义的恶化，但观察到测试之间的一致性较差。需要准确且一致地测量ARIs对CRPC患者身体功能影响的工具。
