Comparison of efficacy and safety of lenvatinib vs. apatinib in combination with hepatic arterial infusion chemotherapy and immune checkpoint inhibitors for unresectable intrahepatic cholangiocarcinoma: A multicenter retrospective study.

e16256 Background: For unresectable intrahepatic cholangiocarcinoma (uICC), combining targeted drugs with chemotherapy (systemic or hepatic arterial infusion chemotherapy, HAIC) and immune checkpoint inhibitors (ICIs) has become a common treatment. However, evidence-based medical evidence to choose between different targeted drugs and ICIs is lacking. This study aims to explore better therapeutic targeted drugs in combination therapy through multi-center real-world data analysis. Methods: This was a multicenter, retrospective analysis of 316 patients with uICC treated with lenvatinib/apatinib combined with HAIC plus ICIs between June 2018 and September 2024. Data were collected from three Chinese centers. Outcomes included overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier methods, overall response rate (ORR) and disease control rate (DCR) using modified RECIST (mRECIST), and adverse events (AEs) rate according to CTCAE v5.0. Propensity score matching (PSM) was performed for: age, sex, tumor size, tumor staging, and nodal staging. Results: Patients were divided into 264 patients receiving lenvatinib combined with HAIC plus ICIs (Group A) and 52 patients receiving apatinib combined with HAIC plus ICIs (Group B). Before PSM, median OS was 22.3 months (95% CI: 16.7-27.9) in Group A and 18.4 months (95% CI: 10.7-26.1) in Group B (HR: 1.483; 95% CI: 0.980-2.243; p = 0.06). Median PFS was 12.2 months (95% CI: 9.8-14.6) for Group A vs. 7.1 months (95% CI: 3.8-10.4) for Group B (HR: 1.437; 95% CI: 0.982-2.104; p = 0.06). Following PSM, 153 patients from Group A and 52 patients from Group B were included. After PSM, Group A showed a significantly higher median OS of 25.3 months (95% CI: 13.5-37.1) compared to 18.4 months in Group B (95% CI: 10.7-26.1; HR = 1.670, 95% CI: 1.066-2.617, p = 0.023). Median PFS was 15.4 months (95% CI: 8.741-22.059) for Group A vs. 7.1 months (95% CI: 3.778-10.422) for Group B, with significantly better PFS in Group A than in Group B (HR = 1.665, 95% CI: 1.105-2.508, p = 0.013). Before PSM, neither ORR (37.5% vs. 24.5%, p = 0.082) nor DCR (89.2% vs. 87.8%, p = 0.774) were significantly different between the two groups according to modified RECIST (mRECIST). After PSM, ORR was higher in Group A than in Group B (40.4% vs. 24.5%, p = 0.046), while no statistical difference was shown between DCR (91.5% vs. 87.8%, p = 0.442). Group B showed a trend towards a lower incidence of grades 3 or 4 AEs compared to Group A (16.7% vs. 9.6%, p = 0.199). Conclusions: Lenvatinib appears to be a better choice for combination therapy in uICC, demonstrating superior OS, PFS, and ORR compared to apatinib. However, apatinib may have a lower incidence of severe AEs. Further prospective studies with larger patient populations are required.