Yu JunJie, Zhou KaiChen, Wang JunQi, Mao LiJun
Department of Urology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China,
Department of Urology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Urol Int. 2025;109(2):167-174. doi: 10.1159/000541929. Epub 2024 Oct 15.
Darolutamide is a structurally unique second-generation androgen receptor antagonist that has been approved for indications in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC). The aim was to assess the efficacy and safety of Darolutamide for mCRPC.
In this single-center, open-label study, patients with previously untreated mCRPC were enrolled and received androgen deprivation therapy (goserelin acetate 3.6 mg every 28 days) and docetaxel (75 mg per square meter of body surface area every 21 days) with Denosumab (120 mg every 28 days) for bone metastases, Darolutamide (300 mg orally twice daily) in the experimental group, and the control group received the corresponding of placebo. Serum PSA changes were detected and recorded, and imaging changes and adverse events (AEs) were evaluated. The primary endpoints were safety, tolerability, and antitumor efficacy, and the second endpoint was radiographic progression-free survival (rPFS).
Thirty-seven patients with mCRPC were enrolled. The median time to PSA50 in the Darolutamide group was 1.5 months (95% CI: 0.2619-0.9545), significantly lower than that in the placebo group (3.0 months [95% CI: 1.048-3.818], p = 0.0259). The median time to PSA90 in the experimental group was 4 months (95% CI: 0.3094-1.437), 2 months shorter than that in the placebo group (6.0 months [95% CI: 0.6961-3.232]). With the median follow-up of 6 months, the median decrease in serum PSA was -81.8% (range -60.4 to -99.9%) in the Darolutamide group and -69.4% (range -50.3 to -89.6%) in the placebo group. Tumor-related pain and AEs were not increased, and the median rPFS was not reached.
The combination of Darolutamide and docetaxel was well tolerated with more clinically beneficial than docetaxel alone in previously untreated mCRPC. Darolutamide rapidly reduced PSA levels and prolonged rPFS and did not increase the incidence of AEs.
达洛鲁胺是一种结构独特的第二代雄激素受体拮抗剂，已被批准用于非转移性去势抵抗性前列腺癌（nmCRPC）和转移性激素敏感性前列腺癌（mHSPC）患者。本研究旨在评估达洛鲁胺治疗转移性去势抵抗性前列腺癌（mCRPC）的疗效和安全性。
在这项单中心、开放标签研究中，纳入既往未接受治疗的mCRPC患者，给予雄激素剥夺治疗（醋酸戈舍瑞林3.6mg，每28天一次）和多西他赛（75mg/m²体表面积，每21天一次），同时给予地诺单抗（120mg，每28天一次）用于骨转移，试验组给予达洛鲁胺（300mg，口服，每日两次），对照组给予相应安慰剂。检测并记录血清PSA变化，评估影像学变化和不良事件（AE）。主要终点为安全性、耐受性和抗肿瘤疗效，次要终点为影像学无进展生存期（rPFS）。
共纳入37例mCRPC患者。达洛鲁胺组达到PSA50的中位时间为1.5个月（95%CI：0.2619 - 0.9545），显著低于安慰剂组（3.0个月[95%CI：1.048 - 3.818]，p = 0.0259）。试验组达到PSA90的中位时间为4个月（95%CI：0.3094 - 1.437），比安慰剂组短2个月（6.0个月[95%CI：0.6961 - 3.232]）。中位随访6个月时，达洛鲁胺组血清PSA的中位下降幅度为-81.8%（范围-60.4%至-99.9%），安慰剂组为-69.4%（范围-50.3%至-89.6%）。肿瘤相关疼痛和不良事件未增加，中位rPFS未达到。
在既往未接受治疗的mCRPC患者中，达洛鲁胺与多西他赛联合使用耐受性良好，比单独使用多西他赛具有更多临床益处。达洛鲁胺可迅速降低PSA水平，延长rPFS，且不增加不良事件发生率。
