Background: Standard first-line treatment of aUC is cisplatin-based chemotherapy, with carboplatin-based chemotherapy or CPI reserved for cisplatin-ineligible individuals. However, given their favorable toxicity profile, there may be an indication drift of first-line CPI into cisplatin-eligible patients, despite no approved indication in this population. Methods: Using the Flatiron Health Database, a nationally representative electronic medical record-based dataset, we examined real-world prescribing patterns of first-line systemic therapies among 2090 patients with aUC diagnosed between the first quarter (q) of 2015 and 2018q1. Our analysis of cisplatin-eligible individuals excluded patients with pre-treatment (1) Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, (2) creatinine ≥ 1.5 mg/dL, or (3) diagnostic codes for chronic renal failure, congestive heart failure, hearing loss, or peripheral neuropathy. We used nonparametric tests of trend to describe first-line CPI and chemotherapy use over time. Results: Between 2015 and 2018, the quarterly proportion of patients who received first-line CPI increased from 1.4% to 43%, while the proportion who received platinum-based chemotherapy decreased from 89% to 56% (p_trend< 0.001) Similarly, among cisplatin-eligible patients (n = 1181), the proportion of first-line CPI users increased from 1.0% in 2015q4 to 42% in 2018q1 (p_trend= 0.001), while the proportion of first-line cisplatin users fell from 53% in 2015q4 to 33% in 2018q1 (p_trend= 0.018). First-line CPI initiators were older (median age 76 vs 71) and had worse performance status (PS ≥ 2 17.8% vs 11.4%) relative to platinum initiators (Table). Conclusions: Our analysis suggests a dramatic rise in first-line CPI use, even in patients who may be cisplatin-eligible, for whom first-line CPI is not evidence-based.