Immune Checkpoint Inhibitors and Anti-vascular Endothelial Growth Factor Antibody/Tyrosine Kinase Inhibitors With or Without HAIC for Unresectable HCC With Portal Vein Tumor Thrombosis

The multiple real-world studies have shown that Anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors plus immune checkpoint inhibitors (ICIs) (VEGF/TKI-ICI) does not result in a high response rate or extended survival for patients with extrahepatic metastases, with an objective response rate (ORR) of less than 20%. Therefore, there is an urgent need to explore effective therapeutic strategies that can enhance the combined antitumor efficacy of (VEGF/TKI-ICI) and improve the prognosis of patients with advanced hepatocellular carcinoma (HCC) with PVTT. In addition to VEGF/TKI-ICI, more aggressive treatments, such as hepatic arterial infusion chemotherapy (HAIC), have been adopted in the Asia-Pacific region. HAIC significantly increases drug concentration in HCC tissues while decreasing drug distribution in the peripheral blood, thereby improving intrahepatic tumor control and reducing systemic adverse events (AEs). Recent significant advancements have been reported in both local-regional and systemic therapies. Furthermore, the combination of HAIC with VEGF/TKI-ICI (HAIC-VEGF/TKI-ICI) may provide potential synergistic anticancer activity for HCC based on the following rationale: HAIC can effectively kill tumors while promoting the release of tumor antigens, thus transforming "cold tumors" into "hot tumors." At the same time, VEGF/TKI can reverse the tumor neovascularization induced by interventional therapies and enhance tumor vasculature normalization. However, it remains unclear whether patients with advanced HCC can benefit from HAIC-VEGF/TKI-ICI through intrahepatic lesion control, thereby impeding tumor progression. Accordingly, this national multiple-centers retrospective study aims to compare the clinical benefits and tolerability of HAIC-VEGF/TKI-ICI versus VEGF/TKI-ICI alone.