Background: Advanced urothelial carcinoma (aUC) has a poor long-term prognosis. Despite new clinical trial data for novel therapies including PD-1/L1 inhibitors, data on real-world (RW) treatment patterns and overall survival (OS) in aUC patients (pts) treated with first line (1L) therapy are limited. Methods: This retrospective observational study describes the contemporary RW 1L treatment patterns and OS in aUC pts stratified by cisplatin (cis)-eligibility (based on accepted criteria) and treatment. Data were from the nationwide Flatiron Health longitudinal electronic health record-derived database, comprising de-identified patient-level structured and unstructured data. Eligible pts were adults diagnosed with aUC from May 2016-Oct 2020 and followed until death or end of data availability in July 2021. OS was estimated using Kaplan-Meier methods and compared via multivariable Cox proportional-hazard models adjusted for clinical covariates. Results: Of 4,300 aUC diagnosed pts, 3,311 (77.0%) received 1L treatment; 1836 (55.5%) cis-ineligible, 1475 (44.5%) cis-eligible. Differences between cis-ineligible and cis-eligible pts were observed, with cis-ineligible more likely to be older (mean age, 75.0 vs 69.0 yrs), have lower CrCl (median, 45.3 vs 80.7 mL/min), and worse ECOG-PS (2+, 29.2 vs 0%). Only 44.4% received 2L therapy: 38.3% cis-ineligible vs 52.0% cis-eligible. Median OS in all 1L treated pts was 11.0 (95% CI, 10.3 – 11.5) mo and was shorter in cis-ineligible than cis-eligible pts (8.6 [95% CI, 8.1 – 9.2] vs 14.4 [95% CI, 13.4 – 16.4]; hazard ratio [HR], 0.8 [0.7 – 1.0]). A number of cis-ineligible pts received cis, and many cis-eligible pts did not (Table), suggesting physicians consider clinical factors beyond conventional criteria to determine cis-eligibility. Cis + gemcitabine (gem) or MVAC was associated with longer OS vs other treatments regardless of cis-eligibility (Table). Conclusions: Clinical outcomes in 1L aUC pts were poor, particularly for cis-ineligible pts, which may be partly driven by the specific regimen administered. Many aUC pts did not receive 1L treatment and among those who did, less than half received 2L therapy. These data highlight the need for more effective and tolerable 1L therapy for all aUC pts.

HR adjusted for cis-eligibility, primary cancer site, age, sex, ECOG-PS, smoking status, PD-L1 status, and CrCl.