Muniz Miguel, Sartor Oliver, Orme Jacob J, Koch Regina M, Scharf Zachary, Heath Elisabeth I, Zarka Jabra G, Kase Adam M, Riaz Irbaz B, Andrews Jack R, Thorpe Matthew P, Tuba Kendi A, Bilgin Gokce Belge, Johnson Geoffrey B, Kwon Eugene D, Childs Daniel S
Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA; Department of Radiology, Division of Nuclear Medicine, Mayo Clinic, Rochester, MN, USA.
Eur Urol Oncol. 2025 Aug 1. doi: 10.1016/j.euo.2025.06.004.
Large clinical trials, including VISION, have established the safety of combining [Lu]Lu-PSMA-617 with an androgen receptor pathway inhibitor (ARPI). Most patients receiving [Lu]Lu-PSMA-617 in the real-world setting have already progressed on an ARPI. This study aimed to assess the efficacy of [Lu]Lu-PSMA-617 in patients with and without the concurrent use of an ARPI.
We analyzed data from the Mayo Clinic Rochester radiopharmaceutical database, focusing on patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed after prior exposure to an ARPI and started treatment with [Lu]Lu-PSMA-617 between March 2022 and March 2023. Patients receiving concurrent ARPIs (abiraterone, enzalutamide, apalutamide, or darolutamide) were identified. Baseline characteristics were compared using Mann-Whitney U test and chi-square test. Outcomes of interest included prostate-specific antigen (PSA) 50 response, median number of cycles, and overall survival (OS) from the start of [Lu]Lu-PSMA-617, analyzed using Kaplan-Meier estimates and multivariate Cox regression.
Among 256 patients, 106 (41.4%) received an ARPI with [Lu]Lu-PSMA-617. Those receiving an ARPI had lower baseline PSA levels (3.4 vs 29.7 ng/ml, p < 0.001) and lower rates of bone (77.4% vs 87.4%, p = 0.035) and visceral (18.9% vs 34%, p = 0.008) metastases. While patients on ARPIs were more likely to complete all six cycles of [Lu]Lu-PSMA-617 (63.2% vs 48.7%, p < 0.001), PSA50 response rates were similar (49.1% vs 47.3%, p = 0.786). Median OS was longer with concurrent ARPI use (not reached vs 15.3 mo, p < 0.001), but this difference was not significant on a multivariate analysis (hazard ratio = 1.03 [95% confidence interval: 0.68-1.55], p = 0.891) after accounting for baseline differences in other prognostic variables. Limitations include its single-center, retrospective design and a lack of standardized radiographic response assessment.
Among men with mCRPC previously exposed to an ARPI, continuation of the ARPI with [Lu]Lu-PSMA-617 did not improve PSA50 response rates or OS after adjusting for cohort imbalances in known prognostic factors. Further post hoc analyses using large clinical trial data are needed.
包括VISION在内的大型临床试验已证实[镥]镥-PSMA-617与雄激素受体通路抑制剂（ARPI）联合使用的安全性。在现实环境中接受[镥]镥-PSMA-617治疗的大多数患者在ARPI治疗上已经进展。本研究旨在评估[镥]镥-PSMA-617在同时使用和未使用ARPI的患者中的疗效。
我们分析了梅奥诊所罗切斯特放射性药物数据库中的数据，重点关注转移性去势抵抗性前列腺癌（mCRPC）患者，这些患者在先前接受ARPI治疗后病情进展，并于2022年3月至2023年3月开始接受[镥]镥-PSMA-617治疗。确定了同时接受ARPI（阿比特龙、恩杂鲁胺、阿帕他胺或达罗他胺）治疗的患者。使用曼-惠特尼U检验和卡方检验比较基线特征。感兴趣的结局包括前列腺特异性抗原（PSA）50反应、中位周期数以及从开始使用[镥]镥-PSMA-617起的总生存期（OS），使用Kaplan-Meier估计和多变量Cox回归进行分析。
在256例患者中，106例（41.4%）在接受[镥]镥-PSMA-617治疗时同时使用了ARPI。同时使用ARPI的患者基线PSA水平较低（3.4 vs 29.7 ng/ml，p < 0.001），骨转移（77.4% vs 87.4%，p = 0.035）和内脏转移（18.9% vs 34%，p = 0.008）发生率也较低。虽然同时使用ARPI的患者更有可能完成[镥]镥-PSMA-617的全部六个周期（63.2% vs 48.7%，p < 0.001），但PSA50反应率相似（49.1% vs 47.3%，p = 0.786）。同时使用ARPI时的中位OS更长（未达到 vs 15.3个月，p < 0.001），但在考虑其他预后变量的基线差异后，多变量分析显示这种差异不显著（风险比 = 1.03 [95%置信区间：0.68 - 1.55]，p = 0.891）。局限性包括其单中心、回顾性设计以及缺乏标准化的影像学反应评估。
在先前接受过ARPI治疗的mCRPC男性患者中，在调整已知预后因素的队列不平衡后，继续使用ARPI联合[镥]镥-PSMA-617并未提高PSA50反应率或OS。需要使用大型临床试验数据进行进一步的事后分析。
