Local-regional therapy plus ICIs, chemotherapy, and lenvatinib versus ICIs plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter study

BACKGROUND: Immune checkpoint inhibitors (ICIs) plus chemotherapy serve as the primary treatment for advanced intrahepatic cholangiocarcinoma (ICC), but they present limited effectiveness. This multicenter study intended to evaluate the feasibility of LRT plus ICIs, chemotherapy, and lenvatinib in patients with advanced ICC. METHODS: Patients receiving LRT-ICIs-Chemotherapy-Lenvatinib (LRT-ICI-Chemo-Len group, N = 66) or ICIs-Chemotherapy (ICI-Chemo group, N = 81) between April 2020 and May 2025 were enrolled. The study's outcomes included progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs). RESULTS: The LRT-ICI-Chemo-Len group showed notable enhancement in median PFS (9.9 months vs. 7.6 months, P = 0.004), median OS (20.9 months vs. 13.7 months, P = 0.004), objective response rate (ORR: 59.1% vs. 27.2%), and disease control rate (DCR: 93.9% vs. 84.0%). Conversion resection was performed in 8/66 (12.1%) in the LRT-ICI-Chemo-Len group, statistically higher than the 2.5% in the ICI-Chemo group. There was no statistically significant difference in the incidence of grade 3-4 AE between the LRT-ICI-Chemo-Len group (65.2%) and the ICI-Chemo group (56.8%) (P = 0.389). The most common grade 3-4 AE in the LRT-ICI-Chemo-Len group was myelosuppression. In the ICI-Chemo group, the most frequent grade 3-4 AE was myelosuppression. All AEs were manageable, with no grade 5 AE observed. CONCLUSIONS: Compared with the ICI-Chemo regimen, the LRT-ICI-Chemo-Len regimen significantly improved the prognosis of patients with advanced ICC. There was no significant difference in the incidence of grade 3-4 AEs between the two treatment regimens, and all AEs were manageable. This indicates that the LRT-ICI-Chemo-Len combination regimen is a feasible approach for the first-line treatment of advanced ICC.