Multi-targeted TKIs combined with immunotherapy are associated with longer survival than bevacizumab combined with immunotherapy in advanced hepatocellular carcinoma

This study aimed to compare the efficacy and safety of multi-target tyrosine kinase inhibitors (TKIs) plus immunotherapy with bevacizumab plus immunotherapy in patients with advanced hepatocellular carcinoma (HCC). 311 HCC patients were included in this study. The patients were grouped according to the usage of targeted drugs. The PSM analysis was employed to eliminate the interference caused by potential confounding variables. Covariate balance was assessed using standardized mean differences (SMDs). Kaplan-Meier analysis and Log-rank test were used to compare the median PFS and OS between the groups before and after the PSM analysis. After PSM analysis, univariate and multivariate Cox regression analyses were used to screen out the risk factors related to prognosis. Subgroup analysis was employed to eliminate the interference caused by potential confounding variables. Before and after PSM analysis, the multi-target targeted drug group had a longer median PFS and OS compared to the bevacizumab-targeted drug group ( P <0.05). After PSM, 188 patients were included in the matched cohort. No statistically significant differences in baseline characteristics were observed between the two groups. After conducting univariate and multivariate Cox analyses, the use of targeted drugs was identified as an important independent risk factor influencing PFS (HR = 1.41, 95% CI 1.03–1.94, P = 0.031) and OS (HR = 2.14, 95% CI 1.50–3.07, P < 0.001). Subgroup analyses generally showed a directionally consistent treatment effect across most clinical subgroups. In this single-center retrospective matched cohort, multi-target TKIs plus immunotherapy were associated with better PFS and OS than bevacizumab plus immunotherapy in patients with advanced HCC. These findings provide preliminary real-world evidence for treatment selection but require further validation in larger multicenter cohorts.