A Network Meta-Analysis Comparing the Efficacy of Lenvatinib, Atezolizumab plus Bevacizumab, and Sorafenib in the Treatment of Unresectable Hepatocellular Carcinoma

INTRODUCTION: Globally, hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer-related death. The five-year overall survival (OS) rate for patients with unresectable HCC is only 12%. Currently, systemic therapies have become the primary treatment options for unresectable hepatocellular carcinoma. Studies comparing the efficacy of first-line treatments including lenvatinib, atezolizumab plus bevacizumab, and sorafenib have shown inconsistent results. There remains a need for updated comparative evidence on cross-mechanism therapy regimens for unresectable disease, as existing findings are still not completely clear. This network meta-analysis aims to provide clearer insights into which treatment offers greater efficacy for patients with unresectable HCC. METHODS: This study was conducted following the 2022 PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Literature searches were performed using PubMed, ScienceDirect, Google Scholar, the Cochrane Library, SpringerLink, and EBSCO to gather studies comparing lenvatinib, atezolizumab plus bevacizumab, and sorafenib for the management of unresectable HCC. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Overall survival (OS) was analyzed using R statistical software (version 4.4.0). RESULTS: Eleven studies reporting overall survival (OS) were included in the OS analysis comparing lenvatinib, atezolizumab plus bevacizumab, and sorafenib in the treatment of unresectable HCC. The network meta-analysis showed no significant OS differences between atezolizumab plus bevacizumab and lenvatinib (HR: 0.98; 95% CI: 0.24-4.10) or sorafenib (HR: 1.4; 95% CI: 0.21-9.87). Furthermore, there was no significant difference in OS between lenvatinib and sorafenib (HR: 1.41; 95% CI: 0.38-5.14). Based on the SUCRA plot in this meta-analysis, atezolizumab plus bevacizumab showed the highest probability of being ranked first among the three therapies. Lenvatinib had the highest probability of being ranked second, while sorafenib was more likely to be ranked third. CONCLUSION: Atezolizumab plus bevacizumab, lenvatinib, and sorafenib demonstrated similar therapeutic efficacy based on overall survival. Although the hazard ratios (HRs) were not statistically significant, the SUCRA ranking suggested a clinical trend favoring atezolizumab plus bevacizumab.