Efficacy and safety of local-regional therapy combined with chemotherapy, immune checkpoint inhibitors and lenvatinib as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study.
Background: Local-regional therapy combined with immune checkpoint inhibitors (ICIs) and lenvatinib has shown promising anti-tumor activity in advanced biliary tract cancer. However, the efficacy and safety of integrating local-regional therapy with chemotherapy, ICIs, and lenvatinib in advanced intrahepatic cholangiocarcinoma (ICC) remain unclear. This study evaluated the efficacy and safety of first-line treatment combining local-regional therapy, chemotherapy, ICIs, and lenvatinib in advanced ICC.
Methods: This multicenter study included 47 advanced ICC patients receiving local-regional therapy (radiotherapy, hepatic arterial infusion chemotherapy, or transarterial chemoembolization) plus chemotherapy, ICIs, and lenvatinib from October 2019 to January 2025. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and prognostic factors analysis.
Results: The multimodal therapy demonstrated mPFS of 10.2 months and mOS of 20.2 months. ORR and DCR reached 61.7% and 93.6%, respectively. Conversion surgery was performed in 10.6% (5/47) of patients, with 60.0% (3/5) achieving sustained remission. All patients experienced AEs, with grade 3-4 AEs in 66.0%, primarily including myelosuppression (23.4%), AST or ALT increased (19.1%), fatigue (14.9%), and pain (10.6%). No grade 5 AEs were observed, and all toxicities were manageable. Survival outcomes, tumor response rates, and grade 3-4 AE incidence showed no significant differences among local-regional therapy subgroups. Multivariate analyses identified impaired performance status as an independent predictor of poorer OS.
Conclusions: The combined regimen of local-regional therapy, chemotherapy, ICIs, and lenvatinib exhibited marked efficacy and a tolerable safety profile, establishing it as a viable first-line approach for advanced ICC.