Hepatic artery infusion chemotherapy combined with lenvatinib and PD-1 inhibitors in the treatment of intermediate and advanced unresectable hepatocellular carcinoma

Systemic treatment for unresectable advanced hepatocellular carcinoma (HCC) primarily comprises targeted therapy and immunotherapy, which have demonstrated improved therapeutic efficacy compared with chemotherapy. However, the overall efficacy for patients remains below expectations. Hepatic artery infusion chemotherapy (HAIC), a novel approach in the treatment of HCC, involves the direct and continuous administration of chemotherapeutic drugs to liver tumors through catheters. The high concentration of chemotherapeutic drugs not only rapidly reduces tumor burden but also induces immunogenic cell death, promoting the release of tumor-associated antigens, tumor-specific antigens and damage-associated molecular patterns. This markedly enhances the infiltration of dendritic cells and antigen-specific CD8+ T cells in the tumor microenvironment, thereby enhancing the antitumor effect of programmed cell death protein 1 (PD-1) inhibitors. Lenvatinib, an anti-angiogenic agent, not only inhibits neo-angiogenesis in hepatic tumor tissues but also effectively mitigates VEGF-mediated immunosuppression. Therefore, the combination of HAIC with lenvatinib and PD-1 inhibitors exhibits a synergistic effect, overcoming the limitations of individual therapies and maximizing overall antitumor efficacy. The present study demonstrated that this triple therapy enhanced the objective response rate (69.7%; 95% CI, 51.3-84.4%) and disease control rate (90.9%; 95% CI, 75.7-98.1%) in patients with unresectable HCC. In terms of survival outcomes, the median progression-free survival with the triple therapy was 9.7 months (95% CI, 9.3-11.6), and the median overall survival was 17.4 months (95% CI, 15.4-24.3). Additionally, the safety profile was favorable, with a low incidence of moderate to severe adverse events, and no treatment-associated mortalities were reported.