Sequential hepatic artery infusion chemotherapy and transarterial chemoembolization combined with anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors and immune checkpoint inhibitors (quadruple therapy) as first-line therapy f

e16180 Background: Sequential hepatic artery infusion chemotherapy (HAIC) and transarterial chemoembolization (TACE) may synergistically increase the drug concentration within the hepatocellular carcinoma(HCC). Moreover, anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors and immune checkpoint inhibitors are widely used in advanced HCC patients. This study aims to evaluate the efficacy and safety of sequential HAIC and TACE combined with targeted therapy and immunotherapy as quadruple first-line treatment for advanced HCC. Methods: This retrospective single-center study recruited data from advanced HCC patients at Zhongshan Hospital, Fudan University, from January 1, 2023 to October 31, 2024. Enrolled patients were treated by sequential FOLFOX-HAIC and TACE combined with anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors (including apatinib in 4 cases, bevacizumab in 4 cases, donafenib in 2 cases, and lenvatinib in 28 cases) and immune checkpoint inhibitors (including PD-1 antibody in 34 cases and PD-L1 antibody in 4 cases). The primary outcome was objective response rate (ORR), evaluated according to RECIST v1.1 and mRECIST criteria. Secondary outcomes included progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: A total of 38 patients (35 [92.1%] men and 3 [7.9%] women) with advanced HCC were enrolled. At the end of this study (November 30, 2024), the ORR was 73.7% (28/38; 95%CI:59.8%-87.6%), and the disease control rate (DCR) was 92.1% (35/38; 95% CI:83.5%-100.0%) based on the RECIST v1.1 criteria. Similarly, according to the mRECIST criteria, the ORR was 86.8% (33/38; 95%CI:76.0%-97.6%), and the DCR was 94.7% (36/38 ;95% CI:87.6%-100.0%). Eleven patients with advanced HCC were down-staged and subsequently achieved curative treatment. With the middle follow-up of 13.0 months, the 12-months OS rate was 84.2%. The median OS and median PFS have not been reached. No grade 5 adverse events were observed in this study. The grade 3/4 adverse events included elevated aminotransferase levels (50.0%), abdominal pain (42.1%), hyperbilirubinemia (36.8%), thrombocytopenia (13.2%), leukopenia (7.9%), rash (5.3%), diarrhea (5.3%), hypokalemia (2.6%), vomiting (2.6%). Conclusions: Sequential hepatic artery infusion chemotherapy and transarterial chemoembolization combined with anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors and immune checkpoint inhibitorsachieved encouraging outcomes with accepted adverse events in advanced HCC patients. These findings warrant further validation in a large randomized clinical trial.