Efficacy and safety of sintilimab and lenvatinib combined with locoregional therapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter cohort study

Abstract

Abstract

Chemotherapy, alone or combined with immune checkpoint inhibitors (ICIs), remains the standard first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC), but survival gains are modest. Triple-combination strategies integrating targeted therapy, ICIs, and locoregional treatment have shown promise in biliary tract cancer, yet sintilimab-based regimens have not been systematically evaluated. This study assessed the efficacy and safety of sintilimab plus lenvatinib and locoregional therapy (triple-regimen) in advanced ICC. In this multicenter retrospective study, 169 patients with advanced ICC received triple-regimen, ICIs plus chemotherapy (ICIs-chemo), or chemotherapy alone between October 2019 and June 2025. Locoregional modalities included external beam radiation therapy, hepatic arterial infusion chemotherapy, and transarterial chemoembolization. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). The triple-regimen was associated with improved survival versus both comparators. Median PFS was 11.9 months with triple-regimen versus 6.0 months with ICIs-chemo ( P < 0.001) and 5.2 months with chemotherapy ( P = 0.007); median OS was 18.7 versus 14.4 and 13.4 months ( P = 0.044 and 0.036), respectively. ORR was higher with triple-regimen (53.3% vs 25.0% and 28.1%), while DCR was 84.4%, 85.0%, and 73.4%. Grade 3–4 AEs occurred in 62.2%, 60.0%, and 56.3% of patients in the triple-regimen, ICIs-chemo, and chemotherapy groups, respectively; all toxicities were manageable and no treatment-related deaths occurred. The addition of locoregional treatment to sintilimab and lenvatinib was associated with favorable survival outcomes compared with chemotherapy-based first-line regimens, without a significant increase in the overall incidence of grade 3-4 AEs.This triple-regimen may represent a promising and well-tolerated first-line therapeutic option for patients with advanced ICC.