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

<h3>Background/Aim:</h3> 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. <h3>Patients and Methods:</h3> 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. <h3>Results:</h3> Among 567 patients (152 avelumab, 415 EVP), unmatched analysis showed longer OS with avelumab [35.4 <i>vs</i>. 29.6 months; hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.48-0.93; <i>p</i>=0.017]. Chronic kidney disease (CKD) predicted poorer OS (HR=1.68, <i>p</i>=0.006); in CKD patients, OS favored avelumab maintenance (26.5 <i>vs</i>. 16.8 months; HR=0.62, <i>p</i>=0.039). <h3>Conclusion:</h3> Avelumab maintenance following platinum chemotherapy achieved better or comparable OS <i>versus</i> EVP, particularly in patients with CKD. These results support individualized treatment selection based on renal function and patient fitness.