¹⁷⁷ Lu-vipivotide tetraxetan PSMA vs cabazitaxel in metastatic castration-resistant prostate cancer: A real-world analysis using the TriNetX database.

e17065 Background: 177 Lu-vipivotide tetraxetan prostate-specific membrane antigen ( 177 Lu-PSMA) has shown promising results in clinical trials for patients with metastatic castration-resistant prostate cancer (mCRPC). However, real-world data comparing 177 Lu-PSMA to other third-line agents, such as Cabazitaxel, is sparse. We aim to evaluate the efficacy and tolerability of 177 Lu-PSMA as a third-line treatment for mCRPC compared to Cabazitaxel. Methods: Using the TriNetX database, we identified patients aged ≥18 with mCRPC from 1/1/2010 to 12/31/2024. Patients were stratified into four groups: Group 1A (Docetaxel → Abiraterone/androgen receptor inhibitor [ARI] → 177 Lu-PSMA), Group 1B (Docetaxel → Abiraterone/ARI → Cabazitaxel), Group 2A (Abiraterone/ARI → Docetaxel → 177 Lu-PSMA), and Group 2B (Abiraterone/ARI → Docetaxel → Cabazitaxel). PSA50 was defined as half of the baseline PSA value, and the percentage of patients achieving PSA ≤ PSA50 over time was analyzed. Propensity score matching (1:1) was performed to adjust for confounding variables, and outcomes were evaluated using risk assessments and Kaplan-Meier survival analyses. Results: Of 77,649 patients with mCRPC, 148 were identified in group 1A, 195 in 1B, 764 in 2A and 871 in group 2B. The median age was 73.4 years for patients receiving 177 Lu-PSMA vs 74.2 years for those receiving Cabazitaxel. In both comparisons, 177 Lu-PSMA demonstrated a significant survival advantage. When comparing groups 1A and 1B, the three-year mortality rate was 23.65% vs 39.04% (HR 0.336, 95% CI: 0.22-0.49, p < 0.0001). When comparing groups 2A vs 2B, the three-year mortality rate was 31.80% vs. 68.21% (HR: 0.56, 95% CI: 0.42-0.76, p=0.0002). Patients on 177 Lu-PSMA achieved PSA50 at higher rates over 0–9 months compared to Cabazitaxel: 40.54% (Group 1A) and 38.46% (Group 2A) vs. 25.68% (Group 1B) and 21.03% (Group 2B). Additionally, 177 Lu-PSMA had significantly lower rates of anemia and fatigue, but a higher incidence of dry mouth [Table 1]. Conclusions: Our real-world analysis demonstrates that 177 Lu-PSMA significantly improves survival and has a more favorable safety profile compared to Cabazitaxel in mCRPC. These findings support its role as a preferred third-line option. However, further large-scale studies are needed to validate these findings in broader patient populations. Incidence of side effects in patients who received 177 Lu-PSMA vs cabazitaxel as a third line agent for mCRPC. Side Effect Group 1A Group 1B HR (95% CI) p-value Group 2A Group 2B HR (95% CI) p-value Anemia 22.95% 53.73% 0.38 (0.20–0.72) 0.0018 23.17% 55.06% 0.40 (0.24–0.69) 0.0006 Fatigue 17.28% 38.16% 0.42 (0.22–0.80) 0.0071 19.57% 32.61% 0.63 (0.35–1.13) 0.118 Dry Mouth 9.72% 6.90% 7.81 (1.77–34.39) 0.0013 12.57% 5.29% 27.569 (3.72–203.88) < 0.0001 Neutropenia 8.55% 10.42% 0.57 (0.18–1.79) 0.33 6.33% 15.20% 0.26 (0.10–0.65) 0.002