Background: In July 2020, the FDA approved avelumab, an immune checkpoint inhibitor (ICI), for maintenance treatment of aUC that has not progressed with first-line (1L) platinum-containing chemotherapy (chemo). Availability of avelumab may have influenced upstream treatment selection between 1L chemo and 1L ICI (pembrolizumab or atezolizumab). We described avelumab use in real-world practice and determined whether 1L treatment choice changed following its approval. Methods: This cohort study used Flatiron Health’s nationwide de-identified EHR-derived database. Included patients started 1L therapy for aUC in the US before (April 1 2017 to June 30 2020) or after (July 1 2020 to May 31 2022) avelumab approval. We calculated the proportion of patients initiating 1L chemo (carboplatin- or cisplatin-based) or ICI during the pre- and post- avelumab approval periods. Time trends were estimated using multinomial logistic regression for 1L treatment choice regressed on time modeled via a natural cubic spline, allowing for a discontinuity in the time trend at the time of FDA approval. Differences in probabilities of 1L treatment in July 2020 (immediately following approval) compared to June 2020 (immediately prior to approval) were calculated. Maintenance avelumab use was described among patients treated with 1L chemo in the post-approval period, and in a sensitivity analysis, among ‘maintenance eligible’ patients defined as those who were progression-free 28 weeks after 1L chemo start. Results: Among all 1L treatment initiators (n=3,507), the FDA approval of maintenance avelumab was followed by increased use of 1L carboplatin-based chemo (+9.9%; 95% CI 1.1-17.2%) but no significant changes in the use of ICI (-5.8%; 95% CI -15.9-4.4%) or cisplatin-based chemo (-4.2%; 95% CI -12.7-5.2%) (Table). Among patients treated with 1L platinum-chemo (n=485), probability of initiating maintenance avelumab increased over time. In the 22 months after approval, approximately 20.4% (n=99/485) of all 1L chemo-treated patients and 24.3% (n=78/321) of maintenance eligible patients received maintenance avelumab. Conclusions: We found modest uptake of maintenance avelumab for aUC after FDA approval. Potential reasons include limited clinician awareness of maintenance immunotherapy and/or patient preferences against long-term treatment after response to initial chemo. Our finding of higher treatment starts with carboplatin-based chemo in the post-maintenance period suggests increasing preference by clinicians of a strategy that provides patients an opportunity for two effective treatment options. Real-world data can provide important insights on community response to regulatory approvals.