Hepatic Arterial Infusion Chemotherapy Plus Systemic Chemotherapy, Lenvatinib and PD-(L)1 Inhibitors Versus Systemic Chemotherapy Plus PD-(L)1 Inhibitors in Advanced Intrahepatic Cholangiocarcinoma.

IntroductionThe prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) remains poor. This retrospective study aims to evaluate the efficacy and safety of HAIC combined therapy in advanced ICC.MethodsBetween April 2021 and July 2024, patients with advanced ICC treated with either HAIC of oxaliplatin plus systemic chemotherapy of gemcitabine, lenvatinib and PD-(L)1 inhibitors (HSLP) or systemic chemotherapy plus PD-(L)1 inhibitors (SP) were consecutively enrolled. Propensity score matching (PSM) was used to minimize selection bias. Primary endpoint was objective response rate (ORR) and secondary endpoints included overall survival (OS), progression-free survival (PFS) and safety.ResultsA total of 110 patients were recruited in this study with 53 in HSLP group and 57 in SP group. Prior to PSM, ORR was significantly higher (47.2% vs. 24.6%; P = 0.023) and both median OS and PFS were prolonged in HSLP group compared to SP group (OS: 15.2 vs. 12.3 months, P = 0.002; PFS: 11.3 vs. 7.3 months, P = 0.004). After 1:1 PSM, outcomes remained superior in the HSLP group, with a significantly higher ORR (43.2% vs. 18.9%; P=0.032) and longer median OS (15.4 vs. 11.8 months; P=0.018) and PFS (11.9 vs. 6.9 months; P=0.019). Multivariate analysis identified the treatment regimen as an independent prognostic factor for OS and PFS. All events were manageable with supportive care, and no additional toxicities were observed in the HSLP group.ConclusionHAIC plus systemic chemotherapy, lenvatinib and PD-(L)1 inhibitors represents a promising therapeutic regimen for advanced ICC patients, with tolerable toxicity.