To investigate the efficacy and safety of different treatments for unresectable intrahepatic cholangiocarcinoma (ICC).

Literature search was performed from PubMed database to find all studies in English related to the treatment of unresectable ICC by subject words combined with free words. The key words were cholangiocarcinoma, cholangiocellular carcinoma, unresectable, advanced, hepatic arterial infusion chemotherapy/HAIC, chemotherapy, radiotherapy, transarterial radioembolization/TARE, transarterial chemoembolization/TACE, PD-1/PD-L1 and protein kinase inhibitors, etc. The retrieval time was from January 1 to June 1, 2024. The primary endpoints were 1-, 2- and 3-year overall survival (OS) rate, and the secondary endpoints were objective response rate (ORR), median progression-free survival (PFS) and incidence rate of adverse reactions. Meta-analysis was carried out by Stata 17.0 software. Treatment methods included chemotherapy, combination therapy, FOLFOX-hepatic arterial infusion chemotherapy (HAIC), immunotherapy, radiotherapy, TACE and yttrium-90 (Y-90).

A total of 43 articles comprising 8 538 patients were included for meta-analysis. Meta-analysis showed that the 1-, 2- and 3-year OS rates in the HAIC and combination therapy groups were 70.2%, 44.4%, 16.9%, and 65.0%, 27.8%, 19.9%, respectively. The 1-, 2- and 3-year OS rates in the TACE, Y-90 and chemotherapy groups were 43.0%, 24.4%, 19.9%, and 45.4%, 19.3%, 10.3%, and 38.0%, 12.6% and 4.9%, respectively. The 1- and 2-year OS rates in the immunotherapy and radiotherapy groups were 65.0%, 19.0%, and 3.6%, 1.5%, respectively. Patients in the TACE, combination therapy and HAIC groups obtained the highest ORR of 50.8%, 47.4% and 45.3%, respectively. The median PFS in the combination therapy group was the longest up to 6.76 months, followed by 4.39 and 4.09 months in the chemotherapy and HAIC groups. The most common adverse reaction was elevated AST/ALT ratio, accounting for 56.6%. Severe adverse reactions were cholestasis (3.0%) and peptic ulcer (0.8%).

For patients with unresectable ICC, FOLFOX-HAIC yields higher efficacy, similar adverse reactions, less severe adverse reactions and high safety compared with alternative treatment options.