Efficacy and Safety of TACE-HAIC Combined with Molecular Targeted Therapy and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma

Purpose: To evaluate the efficacy and safety of a quadruple regimen of transarterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC) plus molecular targeted therapy (MTT) and immune checkpoint inhibitors (ICIs) for unresectable hepatocellular carcinoma (uHCC). Patients and Methods: 274 uHCC patients were divided into two groups based on two treatment methods:TACE-HAIC combined with MTT and ICIs (THTI) and TACE combined with MTT and ICIs (TTI). The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). Results: After Propensity score matching (PSM), the THTI group significantly prolonged median PFS (14.0 vs 10.6 months, P< 0.001) and median OS (30.8 vs 24.8 months, P = 0.001) compared with the TTI group. Compared with the TTI group, the THTI group demonstrated significantly superior ORR (64.5% vs 44.9%, P=0.004) and DCR (94.4% vs 84.1%, P=0.015). In addition, responses to THTI (THTI-R) had superior median PFS (17.1 vs 13.8 months, P = 0.007) and median OS (38.1 vs 27.5 months, P = 0.002) versus responses to TTI (TTI-R). All adverse events were manageable in two groups. Conclusion: For patients with uHCC, the THTI quadruple therapy demonstrated a superior clinical benefit over current TTI triple therapy, including significant prolongation of both PFS and OS, as well as improvements in ORR and DCR, with a manageable safety profile.