Efficacy and Safety of Sorafenib or Lenvatinib for Advanced Hepatocellular Carcinoma after Failure of First-Line Atezolizumab Plus Bevacizumab: A Systematic Review and Meta-Analysis

Simple Summary: Although atezolizumab plus bevacizumab is the standard first-line treatment for patients with advanced HCC, the optimal second-line regimen remains unknown. In this meta-analysis, we examined the subsequent regimen after the failure of atezolizumab-bevacizumab and found that sequential multitargeted tyrosine kinase inhibitors, including sorafenib and lenvatinib, significantly prolonged the survival of patients, with a pooled OS of 11.45 months and a PFS of 3.78 months, respectively. Moreover, the subsequent use of sorafenib or lenvatinib has manageable toxicity. Therefore, our data indicate that sorafenib or lenvatinib treatment is a rational option for patients with advanced HCC after progression on atezolizumab-bevacizumab. Background: Although atezolizumab plus bevacizumab (hereinafter, atezolizumab-bevacizumab) is the standard first-line treatment for patients with advanced HCC, the optimal second-line regimen remains unknown. This study evaluated the efficacy and safety of sorafenib and lenvatinib in patients with advanced HCC that progressed under atezolizumab-bevacizumab treatment. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed, Embase, and the Cochrane Library for articles published before November 2023. Random-effects meta-analysis was performed to determine the pooled objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), comparing patients who received sorafenib versus lenvatinib. Results: Seven studies involving 387 patients were included. The pooled ORR, DCR, OS, and PFS for sorafenib and lenvatinib together were 26% (95% CI: 14-43%), 63% (95% CI: 47-77%), 11.45 months (95% CI: 7.12-15.77, I-2 = 92%, p < 0.01), and 3.78 months (95% CI: 2.34-5.23, I-2 = 67%, p = 0.02), respectively. Although lenvatinib users had a longer median OS (12.42 vs. 10.75 months) and PFS (5.15 vs. 2.58 months) than sorafenib users, the pooled ORR, DCR, median OS, and PFS for these medications were comparable. Additionally, the distributions of all-grade and grade >= 3 adverse events for sorafenib and lenvatinib were comparable to those for these two medications when used as first-line therapies. Conclusions: Sorafenib or lenvatinib can provide effective treatment with manageable toxicity in patients with advanced HCC after disease progression under atezolizumab-bevacizumab.