Background: EV is FDA approved for the treatment of aUC after disease progression with chemotherapy and/or ICI, and in combination with Pembrolizumab (P) for cisplatin ineligible pts in the first line. Reported response rate (RR) for EV+P is higher than EV alone and a retrospective study showed prior ICI is associated with higher grade of EV-related skin toxicity, suggesting immunogenic interaction. Herein we evaluated whether prior ICI correlates with improved response to EV monotherapy. Methods: This single-center retrospective study compared outcomes between pts with aUC who were treated with ICI immediately prior to EV (iICI) vs pts who did not receive immediate prior ICI (niICI). We also evaluated outcomes in pts who received ICI at any time prior to EV, with or without intervening treatments, compared to pts who never received ICI. Demographics and treatment details were extracted through chart review. RR (Complete Response + Partial Response) were compared between groups using χ² test. Univariable and multivariable Cox regression models were used for comparing Progression free (PFS) and Overall (OS) survival. Multivariable models were adjusted for visceral metastasis presence and performance status (PS) at EV initiation (C1D1). Results: We identified 55 pts in the iICI group and 23 in the niICI. Table 1 summarizes patient characteristics. ICIs included Pembrolizumab, Atezolizumab, Nivolumab, and Avelumab. Median PFS for EV was 5.0 vs 2.0 months and OS 11.0 vs 7.1 months in iICI vs niICI group respectively. A statistically significant Hazard Ratio (HR) for PFS [HR: 1.72, 95% Confidence Interval (95CI): 1.03, 2.89, P=0.04] and OS (HR: 2.02, 95CI: 1.13, 3.60, P=0.02) was found in the univariable analysis. In the multivariable analysis HR was 1.56 (95CI: 0.91, 2.68, p= 0.11) for PFS and 1.79 (95CI: 0.97, 3.30, p=0.06) for OS. RR to EV was 43.6% (95CI: 0.33, 0.56) vs 43.5% (95CI: 0.14, 0.69), P= 0.99. In our cohort 70/78 (89.7%) pts received ICI prior to EV with or without intervening treatments. When comparing these pts to pts who never received ICI no significant difference was found in PFS, OS or RR. Conclusions: In our study, EV was associated with longer PFS and OS when given immediately after ICI compared to following other therapies. However, in the most parsimonious model examined, the p-value did not reach a significance threshold of p<0.05. Larger prospective studies are needed to better understand the mechanism behind this trend and identify the optimal sequence or combination of EV with other treatments in aUC.