Overall Survival in Real-World Patients with Unresectable Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab Versus Sorafenib or Lenvatinib as First-Line Therapy: Findings from the National Veterans Health Administration Database

<b>Background/Objectives:</b> This study evaluated comparative overall survival (OS) of United States veterans with unresectable hepatocellular carcinoma (uHCC) receiving first-line (1L) atezolizumab plus bevacizumab vs. sorafenib or lenvatinib, overall and across racial and ethnic groups. <b>Methods:</b> In this retrospective study, patients with uHCC who initiated atezolizumab plus bevacizumab (post-2020) or sorafenib or lenvatinib (post-2018) were identified from the Veterans Health Administration National Corporate Data Warehouse (1 January 2017-31 December 2022). Patient characteristics were evaluated in the year prior to 1L treatment initiation. Kaplan-Meier and multivariable Cox regression methods were used to compare OS starting from treatment between cohorts, both overall and by race and ethnicity. <b>Results:</b> Among the 1874 patients included, 405 (21.6%) received 1L atezolizumab plus bevacizumab, 1016 (54.2%) received sorafenib, and 453 (24.2%) received lenvatinib, with a median follow-up time of 8.5, 7.6, and 8.2 months, respectively. Overall, patients receiving atezolizumab plus bevacizumab had longer unadjusted median OS (12.8 [95% CI: 10.6, 17.1] months) than patients receiving sorafenib (8.0 [7.1, 8.6] months) or lenvatinib (9.5 [7.8, 11.4] months; both log-rank <i>p</i> < 0.001). After adjustment, atezolizumab plus bevacizumab was associated with a reduced risk of death by 30% vs. sorafenib (adjusted HR: 0.70 [95% CI: 0.60, 0.82]) and by 26% vs. lenvatinib (0.74 [0.62, 0.88]; both <i>p</i> < 0.001). OS trends in the White, Black, and Hispanic patient cohorts were consistent with that of the overall population. <b>Conclusions:</b> Atezolizumab plus bevacizumab was associated with improved survival outcomes compared with sorafenib and lenvatinib in patients with uHCC, both overall and across racial and ethnic subgroups.