Hepatic arterial infusion chemotherapy plus targeted therapy and immunotherapy versus systemic chemotherapy for advanced intrahepatic cholangiocarcinoma: a retrospective cohort study

Background: To improve the prognosis of advanced intrahepatic cholangiocarcinoma (iCCA), we retrospectively compared the effect and safety of combined hepatic arterial infusion chemotherapy (HAIC), targeted therapy and immunotherapy with systemic chemotherapy (SC) in unresectable iCCA patients. Methods: We retrospectively enrolled 202 advanced iCCA patients treated with SC or targeted therapy, immunotherapy, and FOLFOX-HAIC combined between March 2015 and June 2023 at our institution. 202 patients were divided into two groups based on the therapeutic regimens. Baseline characteristics and prognosis were reviewed and analyzed. Results: After 1-to-1 propensity score matching, 76 patients were included in each group. The triple combination therapy group demonstrated longer median overall survival (OS, 20.77 vs. 14.83 months, P =0.047), progression-free survival (PFS, 9.07 vs. 6.23 mo, P <0.001), intrahepatic PFS (11.03 vs. 6.73 mo, P <0.001), extrahepatic PFS (11.37 vs. 7.13 months, P =0.0064), and a higher objective response rate (35.5% vs. 14.5%, P =0.003) than the SC group. Fever, thrombocytopenia, elevated ALT, elevated AST, hypoalbuminemia, and hyperbilirubinemia were more common adverse events (AEs) in the triple combination therapy group, while fatigue and anemia were more prevalent in the SC group ( P <0.05). For grades 3-4 AEs, the rates of elevated ALT were higher in the triple combination group ( P =0.028). Conclusions: Compared with SC, triple combination therapy comprising HAIC, targeted therapy and immunotherapy appears to be an effective and safe treatment for advanced iCCA.