177Lu-vipivotide tetraxetan (PSMA-617) vs cabazitaxel in metastatic castration-resistant prostate cancer: a...

177Lu-vipivotide tetraxetan prostate-specific membrane antigen (177Lu-PSMA-617) has shown promising results in clinical trials for patients with metastatic castration-resistant prostate cancer (mCRPC). However, real-world data comparing 177Lu-PSMA-617 to other third-line agents, such as cabazitaxel, is sparse. 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] → 177Lu-PSMA-617), Group 1B (Docetaxel → Abiraterone/ARI → Cabazitaxel), Group 2A (Abiraterone/ARI → Docetaxel → 177Lu-PSMA-617), and Group 2B (Abiraterone/ARI → Docetaxel → Cabazitaxel). Propensity score matching (1:1) was performed to adjust for confounding variables, and outcomes were evaluated using risk assessments and Kaplan-Meier survival analyses. Of 77,649 patients with mCRPC, 170 were identified in Group 1A, 754 in 1B, 233 in 2A and 851 in Group 2B. Primary outcomes included overall survival at 1, 2, and 3 years, with secondary outcomes assessing rates of anemia, fatigue, neutropenia, and dry mouth. Kaplan-Meier analyses revealed significantly improved survival in the 177Lu-PSMA-617 groups, with 3-year survival rates of 21.6% (1A) and 28.5% (2A) compared to 16.3% (1B) and 10.7% (2B) in the cabazitaxel groups (p < 0.0001). 177Lu-PSMA-617 was also associated with a more favorable toxicity profile, with reduced rates of anemia and fatigue. However, dry mouth was more frequent, although these toxicity findings should be interpreted cautiously given the event rarity. These survival benefits were consistent with mean PSA reductions observed in the 177Lu-PSMA-617 groups, further supporting its efficacy. Our real-world analysis demonstrates that 177Lu-PSMA-617 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 and explore long-term outcomes.