## 2 Methods
### Study Measures  
Patient demographics and clinical characteristics were described from the date of la/mUC diagnosis or index date. Patterns and sequencing were described for 1L, 1 LM, 2L, and third-line (3L) treatments. LOTs were defined based on the oncologist-defined LOT rules built into the Flatiron Health database. The rules are as follows: (1) the first eligible therapy was received after or up to 14 days before the index date and after the start of the patient's structured activity; (2) receipt of the first eligible therapy plus other eligible therapies was given within 28 days; (3) across all drugs that make up a LOT, a gap of >120 days between any 2 sequential recepits of therapy would advance the LOT number; (4) for the most recent LOT, the end date was defined as the last date of patient-level structured activity or death, whichever occurred first; and (5) for earlier LOTs, the end date was the day before the start date of the next LOT. Avelumab's use as 1 LM was defined using the algorithm defined in inclusion criteria 8-10. Treatment sequences for each patient were assessed from 1L to 1 LM (pre-index) to 2L (post-index) to 3L (post-index), based on the treatment groups within each line. Sequences were reported as a categorical variable (n, %).  
Clinical outcomes included best response to treatment, objective response rate (ORR), real-world OS (rwOS), real-world PFS (rwPFS), time to treatment discontinuation (TTD), and time to next treatment (TTNT). Among patients with several recorded responses to treatment, the best recorded response was considered. Responses were defined by clinicians  
Figure 1: Study design. Abbreviations: 1L, first line.  
as a categorical response to therapy. Best response was reported as real-world complete response (rwCR), real-world partial response (rwPR), or real-world stable disease (rwSD). ORR was calculated as the proportion of patients with a best response of either rwCR or rwPR out of the total number of patients with a recorded response assessment. rwOS and rwPFS were assessed from the start of avelumab 1 LM and the start of 2L EV. rwOS was defined as the interval (months) between initiation of the relevant index treatment until date of death, as documented by the Flatiron Health database. If patients did not have evidence of death, they were censored at last contact in the Flatiron Health database or at study cutoff. rwPFS was defined as the interval (months) between initiation of the relevant index treatment until evidence of first progression or death. If no evidence of progression existed, the interval ended at date of death (any cause) as documented by the Flatiron Health database. If patients did not have evidence of progression or death, they were censored at last contact in the Flatiron Health database, study cutoff, or initiation of a new anticancer therapy leading to a change in LOT. TTD was defined as the time (months) between LOT start date and LOT end date (date of treatment discontinuation or death due to any cause, whichever occurred first). TTNT was defined as the time (months) between LOT start date and next LOT start date or death due to any cause, whichever occurred first.