Background: A+B is the standard first-line (1L) treatment for uHCC based on the IMbrave150 trial, which demonstrated superior efficacy over sorafenib with longer median overall survival (19.2 vs 13.4 months) and progression-free survival (6.8 vs 4.3 months) among patients with Child Pugh (CP) A cirrhosis. Evidence about A+B use and outcomes in routine clinical practice, including in patients with impaired liver function, remains limited. Methods: This retrospective observational study included adult patients who initiated 1L A+B for uHCC within The US Oncology Network between 1/1/2019 and 8/31/2022 (followed through 11/30/2022) using structured and unstructured electronic health records (EHR) based data. CP classes were reported by physicians or derived from risk factors. Kaplan-Meier methods were used to assess real-world overall survival (rwOS) and progression-free survival (rwPFS) from initiation of A+B. Exploratory subgroup analyses were conducted by CP class, albumin-bilirubin (ALBI) grade, liver disease etiology, and race/ethnicity. Results: We identified 374 patients with uHCC who initiated 1L A+B during the study period. Compared with patients enrolled in IMbrave150 (n=336), those treated with A+B in clinical practice were older (median age: 69 vs 64 years), had worse liver function (CP A: 61% vs 100%; ALBI Grade >1: 66% vs 43%), and had poorer performance status (ECOG PS>1: 18% vs 0%). At a median follow-up of 5.6 months, 78% (n=293) had discontinued treatment. Among them, 57% discontinued was progression and 4% discontinued due to toxicity alone. Median rwOS was 13.2 months (95%CI: 9.5–15.9) and median rwPFS was 6.4 months (95%CI: 5.1–7.7). Subgroup results are shown (Table). Conclusions: In community oncology settings, 1L A+B demonstrates effectiveness in diverse patient cohorts, including those with impaired liver function, non-viral liver disease, and racial/ethnic minorities. Predictive biomarkers can help identify subgroups who may most benefit from 1L A+B.

NR=not reached; NH = non-Hispanic; Results for ALBI Grade 3, other race categories, and missing values are not included.