Overall Survival with [177Lu]Lu-PSMA-617 Versus [177Lu]Lu-PSMA I&T: A Propensity Score-Matched Real-World Analysis.
Overall survival was similar for both [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA I&T, but [177Lu]Lu-PSMA-617 showed greater biochemical response rates.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
This study compared overall survival and safety profiles of [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA I&T in 140 chemotherapy-pretreated patients with metastatic castration-resistant prostate cancer. Patients received [177Lu]Lu-PSMA-617 at 7.4 GBq every 6 weeks or [177Lu]Lu-PSMA I&T at 6.0 GBq every 8 weeks. The results indicated comparable overall survival between the two treatment groups.
Abstract
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.
Background
This paper addresses the clinical outcomes and safety profiles of two radiopharmaceutical therapies in patients with metastatic castration-resistant prostate cancer. Prior studies have indicated varying effects of different PSMA-targeted therapies on survival and biochemical response. Understanding these differences is crucial for optimizing treatment protocols in this patient population.
Methods
This was a single-center retrospective matched-pair analysis involving 140 chemotherapy-pretreated patients. Patients were treated with [177Lu]Lu-PSMA-617 (n=70) or [177Lu]Lu-PSMA I&T (n=70). The primary outcomes included overall survival and biochemical response, with secondary outcomes assessing treatment-related toxicity.
Results
The median overall survival was 14 months for [177Lu]Lu-PSMA I&T and 15 months for [177Lu]Lu-PSMA-617, with a hazard ratio of 1.18 (95% CI, 0.79-1.78; P = 0.42). Early PSA response was significantly associated with prolonged overall survival (P < 0.01). The median PSA decline was -58% for [177Lu]Lu-PSMA-617 compared to -14% for [177Lu]Lu-PSMA I&T (P = 0.02). Biochemical response rates were 70% for [177Lu]Lu-PSMA-617 and 54% for [177Lu]Lu-PSMA I&T. Higher baseline lactate dehydrogenase levels were associated with shorter overall survival (hazard ratio, 1.03-1.04 per 10 U/L; P < 0.01).
Interpretation
The findings suggest that while overall survival rates were comparable between the two treatments, [177Lu]Lu-PSMA-617 demonstrated a greater median PSA decline and higher biochemical response rates. However, the clinical significance of the differences in biochemical responses may be limited by the small sample size and retrospective nature of the study. The lack of patient-specific dosimetry data also raises questions about the implications of cumulative radiation exposure on outcomes.
Key findings
- Median OS: [177Lu]Lu-PSMA I&T: 14 mo; [177Lu]Lu-PSMA-617: 15 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).
- Median PSA decline: -58% with [177Lu]Lu-PSMA-617 vs. -14% with [177Lu]Lu-PSMA I&T; P = 0.02.
- Biochemical response rates: 70% with [177Lu]Lu-PSMA-617 vs. 54% with [177Lu]Lu-PSMA I&T.
- Higher baseline levels of lactate dehydrogenase were significantly associated with shorter OS (hazard ratio, 1.03-1.04 per 10 U/L; P < 0.01).
Limitations
- single-center retrospective analysis
- small sample size (n=140)
- lacks patient-specific dosimetry data
- potential selection bias in matched pairs