## 5 Conclusions  
This retrospective observational study of 214 patients with aUC treated with avelumab 1 LM in the Flatiron Health network provides insights into the treatment patterns, sequencing, and clinical outcomes in real-world clinical practice in the post-avelumab 1 LM approval era. This study sets an important baseline for treatment patterns, sequencing, and clinical outcomes amid a rapidly evolving US treatment landscape. Clinical outcomes including survival results are highly consistent with the JB100 clinical trial of avelumab 1 LM vs. best supportive care alone in la/mUC that demonstrated improved outcomes, including in clinically relevant subgroups [6]. The body of evidence is strengthened by several US and European real-world studies and continues to grow with ongoing studies in Europe and the Asia-Pacific region, supporting avelumab 1 LM efficacy in heterogenous patients treated in routine clinical practice. The results from this study support the continued use of avelumab 1 LM following 1L PBC as a recommended therapy per NCCN Guidelines and other international treatment guidelines including the European Societyfor Medical Oncology [36] and the European Association of Urology [37]. Despite the limitations of retrospective analyses, this study provides insights into the sequencing and effectiveness of 2L EV among patients with la/mUC who are treated with avelumab 1 LM after disease control with 1L PBC. Appropriate selection and sequence of therapies may optimize the proportion of patients who will remain well enough to continue therapy if and when there is disease progression during or after 1L therapy. As novel treatments for la/mUC, including pembrolizumab plus EV, are approved and incorporated into clinical practice, further research is needed to understand optimal treatment sequencing, thereby maximizing clinical outcomes in the real-world setting. Conceptualization, H.H.M., M.K., S.H.M., C.I. and V.M. ; methodology, H.H.M., M.K., S.H.M., C.I, V.M., A.R., S.K., H.S., M.B. and G.G.R. ; software, H.S. and M.B. ; validation, A.R., S.K., H.S., M.B. and G.G.R. ; formal analysis, H.H.M., M.K., S.H.M., C.I., V.M., A.R., S.K., H.S., M.B. and G.G.R. ; investigation, H.H.M., M.K., S.H.M., C.I., V.M., A.R., S.K., H.S., M.B. and G.G.R. ; resources, M.K. and G.G.R. ; data curation, H.H.M., M.K., S.H.M., C.I., V.M., A.R., S.K., H.S., M.B. and G.G.R. ; writing--original draft preparation, H.H.M., M.K., S.H.M., C.I., V.M., A.R., S.K., H.S., M.B. and G.G.R. ; writing--review and editing, H.H.M., M.K., S.H.M., C.I., V.M., A.R., S.K., H.S., M.B. and G.G.R. ; visualization, A.R., S.K., H.S., M.B. and G.G.R. ; supervision, M.K. and G.G.R. ; project administration, M.K. and G.G.R. ; funding acquisition, M.K. All authors have read and agreed to the published version of the manuscript. This study was sponsored by Merck (CrossRef Funder ID: 10.13039/100009945). Editorial support was funded by Merck. The IRB approval of this observational study with secondary data use from an existing EHR database was covered by the Flatiron Health parent protocol. This study was exempt from additional IRB approval because it was retrospective, was noninterventional, and used anonymized data provided by Flatiron Health. Informed Consent Statement: Informed consent was waived due to the deidentification of patient data by Flatiron Health prior to access by the researchers of this study. The data supporting the findings of this study are available from Flatiron Health. Requests for data sharing by license or by permission for the specific purpose of replicating results in this manuscript can be submitted to [EMAIL_ADDRESS]. Editorial support was provided by Nucleus Global. Medical writing support was provided by [PERSON], an employee of Genesis Research Group. H.H.M. has provided consulting or advisory services for Merck and Pfizer; has received research funding from Bristol Myers Squibb, Janssen, Seagen, CITN, Nektar, Apollomics, and Merck; and has received funding for travel, accommodation, and expenses from Bayer.