Local-regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter cohort study.

Abstract

Background: Chemotherapy combined with immune checkpoint inhibitors (ICIs) remains the first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC) but is limited by suboptimal efficacy. While local-regional therapy plus ICIs and lenvatinib (triple therapy) has demonstrated antitumor activity in biliary tract cancers, its role in ICC remains unclear. This multicenter study compared the effectiveness and tolerability of this triple therapy versus chemotherapy plus ICIs in advanced ICC.

Methods: Advanced ICC patients receiving first-line local-regional therapy (radiotherapy, hepatic arterial infusion chemotherapy, or transarterial chemoembolization) plus ICIs and lenvatinib or chemotherapy plus ICIs were screened. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs).

Results: A total of 78 patients receiving triple therapy and 70 patients receiving chemotherapy plus ICIs were included. The triple therapy group exhibited significantly prolonged median PFS (10.8 vs. 7.6 months, P = 0.011) and median OS (18.5 vs. 15.0 months, P = 0.040), along with higher ORR (51.3% vs. 27.1%) and DCR (85.9% vs. 81.4%). Grade 3-4 AEs occurred more frequently in the triple therapy group (60.3% vs. 58.6%), this difference lacked statistical significance (P = 0.968). No grade 5 events were reported, and all AEs were manageable. Multivariate analysis identified CEA as an independent prognostic factor for PFS and OS.

Conclusion: Local-regional therapy plus ICIs and lenvatinib demonstrated superior efficacy and manageable toxicity, establishing it as a viable first-line regimen for advanced ICC.