Efficacy and Safety of Lenvatinib versus Atezolizumab Plus Bevacizumab in the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Abstract

Introduction: Hepatocellular carcinoma (HCC), the leading form of primary liver cancer, is strongly associated with liver cirrhosis and major risk factors such as hepatitis B and C, alcohol consumption, obesity, and non-alcoholic fatty liver disease. Despite treatment advancements, survival rates for unresectable HCC remain low. Lenvatinib and the combination of atezolizumab and bevacizumab (ATE/BEV) show promise, but further studies are needed to compare their clinical outcomes. This study aims to assess the efficacy and safety of LEN and ATE/BEV in unresectable HCC patients. Methods: This research was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) strategy. Literature searches were conducted through PubMed, ScienceDirect, Google Scholar, Cochrane Library, SpringerLink, and Ebsco to gather studies on comparing LEN versus ATE/BEV for managing unresectable HCC. The quality assessment was assessed using the Newcastle-Ottawa Scale (NOS). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and treatment-related adverse events (AEs) were evaluated using Review Manager 5.4 and RStudio 2024.04.1. Results: Twelve retrospective studies were included, comprising 6,620 samples. There was no difference in the OS (HR=0.72; 95%CI: 0.44-1.18, p=0.20), PFS (HR=0.90; 95%CI: 0.75-1.07; p=0.23), ORR (OR=1.16; 95%CI:0.86-1.56; p=0.34) and DCR (OR=1.14; 95%CI:0.97-1.34; p=0.12) between groups. Moreover, in viral and non-viral patients group, LEN showed similar OS and PFS compared with ATE/BEV. In terms of safety, LEN exhibited higher incidences of decreased appetite (OR=2.95; 95%CI:1.12-7.79; p=0.03), diarrhea (OR=2.61; 95%CI:2.06-3.32; p<0.00001), fatigue (OR=1.48; 95%CI:1.27-1.73; P<0.00001), hand-foot syndrome (OR=7.73; 95%CI:4.84-12.33; P<0.00001), and showed lower incidences of increased aspartate aminotransferase (OR=0.44; 95%CI:0.28-0.69; p=0.0004) compared to ATE/BEV. Moreover, LEN showed similar AEs in grade ≥ 3 AEs (OR=1.15; 95%CI:0.29-4.55; p=0.84), hypertension (OR=1.39; 95%CI:0.84-2.28; p=0.20), proteinuria (OR=1.10; 95%CI:0.75-1.60; p=0.63) compared to ATE/BEV. Conclusion: LEN was found to be non-inferior to ATE/BEV in terms of OS, PFS, ORR, DCR. However, LEN may be associated with a higher incidence of AEs.