Combination of Hepatic Arterial Infusion Chemotherapy with Tyrosine Kinase Inhibitor Provides Better Survival in Advanced Hepatocellular Carcinoma Patients

Chung-Wei Liu,1 Po-Ting Lin,2,3 Wei Teng,2,3 Wei-Ting Chen,2,3 Chung-Wei Su,2,3 Yi-Chung Hsieh,2,3 Chen-Chun Lin,3,4 Chun-Yen Lin,2,3 Shi-Ming Lin2,3 1Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Branch, Tao Yuan City, Taiwan; 2Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Tao Yuan City, Taiwan; 3College of Medicine, Chang Gung University, Tao Yuan City, Taiwan; 4Department of Gastroenterology and Hepatology, New Taipei Municipal Tucheng Hospital, New Taipei City, TaiwanCorrespondence: Po-Ting Lin, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fu-Hsing Street, Kuei Shan, Tao Yuan City, 333, Taiwan, Tel +886-3-3281200 ext. 8107, Fax +886-3-3272236, Email [email protected]: Hepatic arterial infusion chemotherapy (HAIC) and tyrosine kinase inhibitors (TKI) are widely used to treat unresectable hepatocellular carcinoma (HCC). This study investigated the benefits of combining TKI and HAIC in these patients.Methods: We retrospectively analyzed patients with unresectable HCC treated at Linkou Chang Gung Memorial Hospital between March 2009 and February 2022. The patients were categorized into two groups: HAIC combined with TKI therapy and HAIC alone. Kaplan–Meier analysis, Cox proportional hazards models, and propensity score matching were applied.Results: Among 130 patients, the combination therapy group showed significantly improved overall survival (OS) (20.2 versus 11.8 months, p = 0.000) and progression-free survival (PFS) (8.2 versus 3.6 months, p = 0.011) compared to the HAIC-only group. These advantages persisted after propensity score matching with improved OS (20.2 vs 12.9 months, p = 0.001) and extrahepatic PFS (12.4 vs 5.5 months, p = 0.008). Combination therapy improved PFS in the stage IV portal vein thrombosis (PVT) subgroup. TKI combination therapy, more than nine HAIC cycles, and post-HAIC transarterial chemoembolization (TACE) were independent predictors of improved OS.Conclusion: Combining HAIC with TKI therapy improves survival outcomes compared to HAIC alone in patients with unresectable HCC, especially in cases with extrahepatic spread and PVT. Sequential TACE following HAIC therapy further enhances survival benefits.Keywords: HAIC, TKI, sorafenib, lenvatinib, portal vein thrombosis