Real-world safety among patients with locally advanced or metastatic urothelial cancer (la/mUC) treated with first-line (1L) systemic regimens: Results from the ELEVATE UC-I study.

e16554 Background: Recent advances in the treatment (tx) of la/mUC include immune checkpoint inhibitors (ICIs) and antibody drug conjugates (ADCs) alone or as part of sequential or combination tx. However, data remain limited on real-world tx-emergent adverse events (rwTEAEs) associated with contemporary 1L therapies. This study evaluated the incidence of rwTEAEs among contemporary 1L regimens for la/mUC. Methods: This US-based retrospective cohort study used the Premier Healthcare database to identify patients ≥18 years with la/mUC who initiated 1L therapy between January 2020 and September 2023. Eligible patients were divided into 5 cohorts based on 1L therapy received: enfortumab vedotin + pembrolizumab (EV+P), cisplatin-based regimens (+/- avelumab maintenance), carboplatin-based regimens (+/- avelumab maintenance), or ICI monotherapy. rwTEAEs were calculated as number of events per 1,000 person days on tx to adjust for tx exposure by 1L therapy. Results: Of 6,867 patients included in the study, 73% were male, median (IQR) age was 72 years (64-78), 83% were White and mean (SD) Charlson-Deyo Comorbidity Index was 5.06 (3.43). Median (IQR) follow-up was 140 days (92). The most frequent rwTEAEs were infusion-related reactions (55%), anemia (33%), fatigue (20%), and asthenia (20%). Incidence rates of specific rwTEAEs of interest varied by 1L tx for la/mUC (Table). ICI monotherapy demonstrated low rates of most rwTEAEs. Platinum-based therapies exhibited more hematologic toxicities. EV+P rwTEAEs were notable for fatigue, chemotherapy-induced peripheral neuropathy, rash, and decreased appetite. Conclusions: These findings offer insights into the real-world safety of 1L tx options for patients with la/mUC, highlighting the distinct rwTEAE profiles associated with each regimen. These findings may help inform clinical management and support shared decision-making. Future studies should evaluate rwTEAE incidence rates adjusting for differences in patient demographic and clinical characteristics. rwTEAE incidence rates by 1L tx for la/mUC. 1L Tx Overall Cohort(n=6,867) EV+P (n=87) Cisplatin-based chemo alone (n=3,114) Cisplatin-based chemo + avelumab (n=216) Carboplatin-based chemo alone (n=1,144) Carboplatin-based chemo + avelumab (n=190) ICI monotherapy (n=2,116) Median follow-up time, days 140 149.23 131.93 359.63 117.77 329.63 212.95 Incidence rate (events per 1,000 person days on tx) Fatigue 2.33 3.91 2.15 2.43 2.07 3.18 2.41 Neutropenia 2.03 0.23 3.35 3.34 3.55 2.43 0.14 Diarrhea 0.75 1.69 0.74 0.50 0.64 0.62 0.83 Chemotherapy-induced peripheral neuropathy 0.62 2.97 0.66 1.65 0.61 0.44 0.38 Decreased appetite 0.42 1.02 0.39 0.34 0.67 0.65 0.33 Rash 0.36 2.40 0.17 0.17 0.19 0.32 0.57 Hyperglycemia 0.23 0.62 0.23 0.59 0.21 0.28 0.15