Overall Survival with [177Lu]Lu-PSMA-617 Versus [177Lu]Lu-PSMA I&T: A Propensity Score-Matched Real-World Analysis.

In this study, we compared clinical outcomes and safety profiles of radiopharmaceutical therapy with [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA I&T in patients with metastatic castration-resistant prostate cancer under real-world conditions.

Methods

This single-center retrospective matched-pair analysis included 140 chemotherapy-pretreated patients with metastatic castration-resistant prostate cancer treated with commercially available [177Lu]Lu-PSMA-617 (7.4 GBq every 6 wk) (n = 70) or in-house produced [177Lu]Lu-PSMA I&T (6.0 GBq every 8 wk) (n = 70). Propensity score matching was performed on the basis of age, baseline prostate-specific antigen (PSA), and PSA-positive tumor volume and stratified by Gleason score. Overall survival (OS), biochemical response, prognostic factors, and treatment-related toxicity were analyzed.

Results

Median OS was comparable between matched cohorts ([177Lu]Lu-PSMA I&T: 14 mo; range, 9-16 mo; [177Lu]Lu-PSMA-617: 15 mo; range, 10-21 mo); hazard ratio, 1.18; 95% CI, 0.79-1.78; P = 0.42). Early PSA response was strongly associated with prolonged OS in both cohorts (P < 0.01). Patients treated with [177Lu]Lu-PSMA-617 demonstrated a greater median PSA decline (-58% vs. -14%, P = 0.02) and higher biochemical response rates (70% vs. 54%). Although quantitative hematologic changes were more pronounced with [177Lu]Lu-PSMA-617, Common Terminology Criteria for Adverse Events-graded toxicity remained comparable between cohorts. Multivariable analysis revealed that higher baseline levels of lactate dehydrogenase were significantly associated with shorter OS in both cohorts (hazard ratio, 1.03-1.04 per 10 U/L, P < 0.01).

Conclusion

Treatment with [177Lu]Lu-PSMA I&T and [177Lu]Lu-PSMA-617 resulted in comparable survival outcomes despite different treatment protocols. Greater biochemical responses and subclinical hematologic changes with [177Lu]Lu-PSMA-617 may reflect higher cumulative radiation exposure, although patient-specific dosimetry data were not available to confirm this hypothesis.