The Combination of Atezolizumab and Bevacizumab Versus Lenvatinib as a First-Line Systemic Therapy for Treatment of Hepatocellular Carcinoma: A Real-World Comparison

Introduction: Atezolizumab plus bevacizumab (AB) and lenvatinib (LEN) demonstrate non-inferior survival compared with sorafenib for first-line treatment of unresectable hepatocellular carcinoma (HCC) but have not been directly compared. We retrospectively compared survival outcomes between patients treated with AB and LEN in Canada. Methods: We identified patients with unresectable HCC treated with AB or LEN as first-line systemic therapy from 2018 to 2022 at participating cancer centers. Propensity score matching was used to account for clinicopathologic and treatment-related confounders. Three-year progression-free survival (PFS) and overall survival (OS) were compared before and after matching, and Cox regression assessed the association between first-line therapy and survival outcomes. Results: Among 437 eligible patients, 155 received AB and 282 received LEN. Before matching, AB was associated with improved OS (19.7 vs. 14.4 months; HR = 0.75; 95%CI = 0.58–0.88; p = 0.04), but not PFS (8.2 vs. 6.5 months; HR = 0.89; 95%CI = 0.71–1.12; p = 0.32). After matching, 140 AB-treated and 249 LEN-treated patients remained. AB was associated with improved OS (19.7 vs. 15.0 months; HR = 0.75; 95%CI = 0.58–0.88; p = 0.03), while PFS remained similar (8.4 vs. 6.7 months; HR = 0.89; 95%CI = 0.71–1.12; p = 0.32). Conclusions: First-line AB was associated with improved OS compared with LEN, while PFS was similar. These real-world findings support AB as a first-line option when prioritizing survival.