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.