Effectiveness of Chemotherapy Plus Immunotherapy and Molecular Alterations in Advanced Biliary Tract Cancer: Real-World Evidence From a Single-Center Australian Cohort

Introduction Immune checkpoint inhibitors plus chemotherapy has become the new standard of care for advanced biliary tract cancer (BTC). However, the real-world effectiveness and safety of this approach, and its association with molecular alterations, remains uncertain. Methods In this single institutional retrospective cohort study, patients with advanced BTC treated with systemic chemotherapy with or without immunotherapy from July 2020 to June 2025 were included. Primary endpoint was overall survival (OS) in patients treated with first-line chemoimmunotherapy; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, prognostic factors, and molecular profiling. Results 49 of 52 patients (94.2%) received chemoimmunotherapy. Median OS and PFS were 10.2 months and 5.4 months, respectively; the ORR was 24.5%. Poor Eastern Cooperative Oncology Group (ECOG) performance status and hypoalbuminemia were independent predictors of poor OS. Among the 52 patients, molecular profiling identified IDH1 mutations (9.6%), FGFR2 fusions (3.9%), HER2 amplification (5.8%), dMMR (5.8%), and BRCA mutations (5.8%). HER2 amplification was associated with worse OS; dMMR and BRCA mutations showed a trend toward improved OS. Conclusion Real world first-line chemoimmunotherapy for advanced BTC achieved outcomes comparable to those in pivotal trials. The ECOG performance status, serum albumin level, and HER2 status were prognostic for OS, supporting the importance of baseline patient selection and molecular profiling in treatment planning.