Real-world Analysis of Treatment Patterns, Clinical Outcomes, and Molecular Profiling in Advanced Biliary Tract Cancer

Background/Aim: Real-world data regarding the efficacy of immunotherapy and targeted agents in advanced biliary tract cancer (BTC) remain limited. We evaluated treatment patterns, outcomes, and molecular characteristics in this evolving landscape. Patients and Methods: We retrospectively analyzed clinical data of patients with advanced BTC who initiated palliative systemic therapy at Chung-Ang University Hospital between March 2022 and February 2025. Genomic profiles were evaluated using next-generation sequencing (NGS), and actionable alterations were defined based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) tier I. Results: Among 85 patients included in the analysis, 43 (50.6%) received second-line chemotherapy, and 16 (18.8%) received third-line or later treatments. Immunotherapy was administered to 56 patients (65.9%) during the treatment course, including 38 (44.7%) who received first-line chemoimmunotherapy. NGS was performed in 51 patients (60.0%), and actionable genomic alterations (ESCAT tier I) were identified in eight patients: ERBB2 amplification (n=4), IDH1 mutations (n=2), FGFR2 fusion (n=1), and deficient mismatch repair (n=1). The most frequently observed mutations were TP53 mutations (n=23, 27.1%), followed by KRAS (n=15, 17.6%) and ARID1A (n=8, 9.4%). The median progression-free survival (PFS) for first-line and second-line chemotherapy was 6.5 months 95% confidence interval (CI)=4.35-8.71 and 2.7 months (95%CI=1.76-3.64), respectively. The median overall survival (OS) was 12.1 months (95%CI=7.64-16.6). Notably, within the NGS-tested cohort, patients treated with matched targeted therapy in the second-line setting demonstrated significantly superior outcomes compared to those treated with conventional chemotherapy (median PFS 9.7 vs. 2.1 months; p=0.012; median OS: 27.7 vs. 11.0 months, p=0.026). Conclusion: The integration of NGS and the subsequent use of matched targeted therapy significantly improved survival outcomes in selected patients with advanced BTC, highlighting the importance of precision medicine strategies.