Immunotherapy and Targeted Therapy for Advanced Biliary Tract Cancer

Biliary tract cancer (BTC), encompassing intrahepatic and extrahepatic cholangiocarcinoma as well as gallbladder cancer, represents a heterogeneous group of malignancies characterized by an aggressive clinical course and poor prognosis. Systemic chemotherapy with gemcitabine plus cisplatin has remained the standard first-line treatment for more than a decade because most patients are diagnosed at an advanced or unresectable stage, but the associated survival benefit is limited. Recent therapeutic advances have been driven by the integration of immunotherapy and molecularly targeted approaches. Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinically meaningful activity, particularly in combination with cytotoxic chemotherapy, and are increasingly being incorporated into first-line treatment strategies for advanced BTC. Concurrently, comprehensive molecular profiling has revealed substantial genomic heterogeneity and identified actionable alterations, including fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and human epidermal growth factor receptor 2 (HER2) amplification, enabling the development of precision targeted therapies for selected patient populations. Despite these advances, the therapeutic responses to immunotherapy and targeted agents remain highly variable, and robust predictive biomarkers have yet to be established. Accordingly, optimizing patient selection by integrating molecular and immunologic characteristics has become a critical objective for improving clinical outcomes. This review provides an overview of the recent progress in immunotherapy and targeted therapy for BTC, focusing on pivotal clinical trials, therapeutic efficacy, current limitations, and future perspectives for personalized treatment strategies.