Efficacy and outcomes of [¹⁷⁷Lu]Lu-PSMA-617 in patients with mCRPC treated with or without concurrent ARPI: a real-world single-center analysis.

Abstract

[177Lu]Lu-PSMA-617 was approved after the VISION trial demonstrated significant benefit in metastatic castration-resistant prostate cancer (mCRPC). This study evaluated outcomes of [177Lu]Lu-PSMA-617 with or without concurrent Androgen Receptor Pathway Inhibitors (ARPI) in a real-world setting. We retrospectively analyzed electronic health records of mCRPC patients treated with [177Lu]Lu-PSMA-617 in routine clinical practice between June 2023 and August 2024. Primary endpoints were overall survival (OS) and PSA50 response; secondary endpoints included PSA-progression-free survival (PSA-PFS), radiographic PFS (rPFS), and percentage PSA change from baseline. Baseline characteristics were compared using Mann-Whitney U and chi-square tests. Survival outcomes were evaluated using Kaplan-Meier and Cox regression analyses. Among 108 patients, 65 received [177Lu]Lu-PSMA-617 monotherapy and 43 concurrent ARPI therapy. Baseline characteristics were generally well balanced, with slightly higher hemoglobin and a trend toward lower PSA in the ARPI group. No significant between-group differences were observed for median OS (12.7 vs. 13.5 months; p = 0.96), PSA50 response rate (51.2% vs. 52.3%; p = 0.91), PSA-PFS (6.3 vs. 6.2 months; p = 0.54), or median PSA change from baseline (-39.0% vs. -43.1%; p = 0.24). A non-significant trend in rPFS favored the ARPI group (10.6 vs. 9.8 months; p = 0.057). On multivariable Cox regression, concurrent ARPI use was not independently associated with OS (adjusted HR 1.29; p = 0.33). In this real-world cohort of ARPI- and taxane-pretreated mCRPC patients, concurrent ARPI use during [177Lu]Lu-PSMA-617 was not independently associated with improved clinical outcomes. These exploratory findings do not provide evidence to support routine continuation of ARPI beyond progression at the time of radioligand therapy initiation.