Real-world Comparison of Avelumab Maintenance and Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Carcinoma.

BACKGROUND/AIM: For metastatic urothelial carcinoma (mUC), platinum-based chemotherapy followed by avelumab maintenance and enfortumab vedotin plus pembrolizumab (EVP) are standard first-line strategies. Direct real-world comparisons remain limited. This study aimed to determine whether avelumab maintenance following platinum-based chemotherapy offers comparable or superior survival outcomes to EVP.

PATIENTS AND

METHODS

A retrospective cohort study was conducted using de-identified data from the TriNetX Global Collaborative Network. Adults (≥18 years) with locally advanced or metastatic UC diagnosed between 2005 and 2025 were included if systemic therapy began within six months of diagnosis. Patients undergoing radical surgery or unsuitable for first-line chemotherapy were excluded. Cohorts included EVP, avelumab after cisplatin, and avelumab after carboplatin. Propensity score matching (1:1) balanced demographics and comorbidities. The primary endpoint was overall survival (OS), analyzed using Kaplan-Meier and Cox proportional hazards models.

RESULTS

Among 567 patients (152 avelumab, 415 EVP), unmatched analysis showed longer OS with avelumab [35.4 vs. 29.6 months; hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.48-0.93; p=0.017]. Chronic kidney disease (CKD) predicted poorer OS (HR=1.68, p=0.006); in CKD patients, OS favored avelumab maintenance (26.5 vs. 16.8 months; HR=0.62, p=0.039).

CONCLUSION

Avelumab maintenance following platinum chemotherapy achieved better or comparable OS versus EVP, particularly in patients with CKD. These results support individualized treatment selection based on renal function and patient fitness.