Atezolizumab/Bevacizumab vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study

SIMPLE SUMMARY: This study compared the therapeutic efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). A total of 232 patients from three academic hospitals in Korea were included. No significant differences in objective response rate, overall survival, progression-free survival, or the incidence of adverse events were noted. Similar results were obtained after propensity score matching and inverse probability of treatment weighting analyses. This study makes a significant contribution to the literature because it provides the first comparison of lenvatinib and atezolizumab/bevacizumab for the treatment of unresectable HCC in the real-world setting. ABSTRACT: Lenvatinib (LENV) and atezolizumab/bevacizumab (ATE/BEV) have been approved as first-line regimens for the treatment of unresectable hepatocellular carcinoma (HCC). We aimed to compare their clinical efficacy and safety. Patients receiving ATE/BEV (n = 86) or LENV (n = 146) as first-line treatment were recruited from three academic hospitals in Korea. Overall survival (OS), progression-free survival (PFS), and radiological response were assessed according to the Response Evaluation Criteria in Solid Tumors. Clinical features of the two groups were balanced through propensity score (PS) matching with a 1:1 ratio and inverse probability of treatment weighting (IPTW) analyses. The median age was 62 years, with male predominance (83.6%). There was no significant difference in the objective response rate between the ATE/BEV and LENV groups (32.6% vs. 31.5%; p = 0.868). Neither median OS (not reached vs. 12.8 months; p = 0.357) nor PFS (5.7 vs. 6.0 months; p = 0.738) was different between ATE/BEV and LENV groups. PS-matched and IPTW analyses yielded comparable results in terms of OS and PFS (all p > 0.05). Grade ≥ 3 adverse events occurred in 42.8% and 21.9% of patients in the ATE/BEV and LENV groups, respectively (p = 0.141). The two first-line therapy regimens for unresectable HCC had comparable clinical efficacy and safety in real-world practice settings. Further studies with a larger sample size and longer follow-up are needed to validate these results.