Clinical outcomes in the real-world utilization of 177Lu-PSMA 617 in metastatic castrate-resistant prostate cancer.

Abstract

104 Background: 177Lu-PSMA-617 (177Lu) is an established therapy for PSMA-PET–positive metastatic castration-resistant prostate cancer (mCRPC). We used a large US real-world (RW) dataset to describe utilization and outcomes with 177Lu. Methods: mCRPC pts treated with 177Lu from 23-Mar-2022 to 25-Aug-2025 were included in this study from the deidentified Integra PrecisionQ database. Baseline features (age, race, ECOG performance status, Charlson comorbidity index (CCI), prostate-specific antigen [PSA]) and treatment course (follow-up, number of 177Lu cycles) were collected. A landmark analysis at 9 mo after the first 177Lu dose among pts alive and in care assessed predictors of receiving 1-3 vs. 4-6 cycles using logistic regression. Overall survival (OS) from first 177Lu dose was assessed with Cox proportional hazards models adjusted for prespecified baseline covariates. Missing covariates were handled by complete-case analysis. Results: A total of 1002 pts received 177Lu: 718 had ≥9 mo of follow-up at the landmark, of which 109 (15.2%) were treatment-naïve. Median age was 71 yr (range 65-77). Among the 718 pts, median OS was 15 mo (95% CI 13.3-16.8) and 98 (13.6%) received exactly 1 cycle; 95 (13.2%) received exactly 2 cycles; 95 (13.2%) received exactly 3 cycles; 94 (13.1%) received exactly 4 cycles; 69 (9.6%) received exactly 5 cycles, and 267 (37.2%) received exactly 6 cycles. In multivariable analysis, higher baseline PSA (OR 0.77 per ng/mL; 95% CI 0.70-0.85; P<0.001) and greater comorbidity burden (OR 0.84 per 1-point increase in CCI; 95% CI 0.76-0.94; P<0.001) were associated with receiving fewer cycles (1-3 vs. 4-6). Worse OS outcomes were associated with pre-treatment ECOG 3 vs. 0 (HR 4.02, 95% CI 2.20-7.35; P<0.001) and higher log(PSA) (HR 1.30 per 1 unit; 95% CI 1.22-1.38; P<0.001), while longer time from mCRPC diagnosis to 177Lu initiation was associated with lower hazard (HR 0.99 per month; 95% CI 0.99-1.00; P=0.033). Baseline characteristics are summarized in the table. Conclusions: In RW practice, more than one-third of eligible pts completed six 177Lu cycles. Higher baseline PSA and greater comorbidity burden were associated with receiving fewer cycles, underscoring the value of early risk stratification to maximize completion of full treatment courses with 177Lu. Characteristic/Outcome Total 177Lu Cycles (1-3) n=287/718 Total 177Lu Cycles (4-6) n=431/718 P value Age at treatment (Q1, Q3), yr 73 (65, 78) 71.5 (66, 77) 0.0264 PSA (Q1, Q3), ng/mL 88 (22, 337) 28.5 (7.9, 141.7) <0.0001 Hemoglobin (Q1, Q3), g/dL 10.8 (5.7, 16.4) 11.9 (10.9, 13.2) <0.0001 CCI (Q1, Q3)* 8 (8, 10) 8 (8, 9) 0.005 Overall survival (95% CI), mo 6.1 (5.3, 6.7) 21.1 (19.3, 25.1) <0.0001 *Despite similar median and IQR values, the underlying distributions of CCI scores differed significantly between groups (Wilcoxon rank-sum test, P=0.005).