Comparing first-line (1L) atezolizumab plus bevacizumab (A+B) to lenvatinib (L) or sorafenib (S) in patients with unresectable hepatocellular carcinoma (uHCC): Findings from the National Veteran Health Administration (VHA) database.

Abstract

446 Background: The approval of A+B has reshaped the treatment paradigm for patients with uHCC, establishing a new standard of care for 1L uHCC treatment. The VHA is the largest independent healthcare delivery network and the largest provider of liver-related care in the US. We aimed to compare patient characteristics and clinical outcomes between veterans who received 1L A+B and those who received L or S for unresectable HCC. Methods: Using data from the VHA National Corporate Data Warehouse (1/1/2017 - 12/31/2022), we conducted a retrospective cohort study in patients diagnosed with uHCC who initiated A+B after 2020 or initiated L or S after 2018. Child-Pugh (CP) scores were calculated using a previously validated algorithm. Kaplan-Meier and multivariable Cox regression methods were applied to compare overall survival (OS) between the groups. Results: We identified 405 eligible patients who received A+B, 453 received L, and 1,016 received S. Compared with patients receiving L or S, those treated with A+B had a higher proportion of CP A5 (47% and 35% vs. 54%, respectively; both p<0.05), a similar proportion of A6 (30% and 32% vs. 31%, p=0.683 and 0.681, respectively), a lower proportion of B7 (15% and 20% vs. 9%, respectively; both p<0.05), and a greater comorbidity burden as measured by the mean Charlson Comorbidity Index (CCI) (5.8 [L or S] vs 6.6 [A+B], both p<0.05). Median OS (mOS) was 12.8 months (95% CI: 10.6, 17.1) in the A+B cohort, compared to 9.5 months [95% CI: 7.8, 11.4] in the L cohort, and 8.0 months [95% CI: 7.1, 8.6] in the S cohort. In subgroup analyses, longer mOS was observed with A+B than with L or S in CP A patients and those with ALBI grades 1-2A; similar mOS was observed among those with more severe liver dysfunction (Table). In multivariable analysis, A + B was associated with a 26% lower risk of death relative to L (HR=0.74, 95% CI: 0.62-0.88) and 30% lower risk of death compared to S (HR = 0.70, 95%CI 0.60-0.82), both p<0.001. Conclusions: In a real-world VHA experience with A+B among diverse patient groups, a clinically notable survival benefit was observed with A+B compared to L or S. Future evaluations of the safety of using A+B in patients with greater liver dysfunction, including CP B and cirrhosis, are needed to evaluate the expanded use of A+B. [Table: see text]