A Real-World Study of Precision Treatment for Advanced Cholangiocarcinoma Based on Molecular Subtyping

Inclusion Criteria: 1. Age ≥ 18 and ≤ 75 years. 2. Histologically confirmed, unresectable advanced biliary tract carcinoma, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder cancer (diagnosed according to the 2025 Chinese Society of Clinical Oncology (CSCO) Guidelines for Biliary Tract Malignancies and confirmed by a multidisciplinary team). Must have a documented targetable gene mutation, including but not limited to: Fibroblast Growth Factor Receptor 2 (FGFR2) fusion/rearrangement, Isocitrate Dehydrogenase (NADP(+)) 1 (IDH-1) and Isocitrate Dehydrogenase (NADP(+)) 2 (IDH-2) mutations, Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2/HER2) amplification and/or overexpression, B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF) V600E mutation, Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutation, Neurotrophic Tyrosine Receptor Kinase (NTRK) fusion, Rearranged during Transfection (RET) fusion, Ring Finger Protein 43 (RNF43) mutation, MET Proto-Oncogene, Receptor Tyrosine Kinase (MET) amplification, Epidermal Growth Factor Receptor (EGFR) mutation, Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) mutation, BRCA1 DNA Repair Associated (BRCA1)/BRCA2 DNA Repair Associated (BRCA2) mutation, Partner and Localizer of BRCA2 (PALB2) mutation, Vascular Endothelial Growth Factor Receptor (VEGFR) mutation, deficient Mismatch Repair (dMMR)/Microsatellite Instability-High (MSI-H), or Neuregulin 1 (NRG1) mutation. 3. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (measurable lesion defined as longest diameter ≥10 mm on Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) scan). 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 5. Child-Pugh class A or B liver function. For patients with obstructive jaundice, total bilirubin must be ≤ 50 µmol/L. Biliary drainage is recommended if total bilirubin is \> 50 µmol/L. 6. Adequate hematologic function: Absolute Neutrophil Count (ANC) ≥ 1.5 × 10\^9/L, Hemoglobin (Hb) ≥ 8.5 g/L, Platelets (PLT) ≥ 75 × 10\^9/L. 7. No history of severe arrhythmia or heart failure; no severe ventilation dysfunction or severe pulmonary infection; no acute or chronic renal failure with creatinine clearance \> 40 mL/min. 8. Life expectancy of more than 3 months. Exclusion Criteria: 1. Major surgery within 28 days prior to enrollment. 2. Presence of any unresolved toxicity of Grade ≥ 2 (according to Common Terminology Criteria for Adverse Events \[CTCAE\] v4.0) from prior anticancer therapy at the time of enrollment, with the exception of alopecia or Grade 2 anemia. 3. Known hypersensitivity to any components or excipients of the study drugs. 4. Presence of any active autoimmune disease or a history of autoimmune disease with an expected recurrence. Patients currently receiving immunosuppressants or systemic corticosteroids for immunosuppressive purposes. 5. Presence of other concurrent malignancies. 6. Presence of brain metastases or spinal cord compression. 7. Presence of any severe and/or unstable pre-existing medical conditions, mental illness, or other conditions that could compromise patient safety, the ability to provide informed consent, or adherence to the study procedures. 8. Pregnant or breastfeeding women. 9. History of organ transplantation. 10. Patients with proteinuria ≥ 1+ on urinalysis must undergo a 24-hour urine protein test. Patients with a 24-hour urine protein level ≥ 1g are excluded. 11. Clinically significant corneal or retinal disease confirmed by ophthalmologic examination. 12. Liver tumor burden exceeding 50%. 13. Hypothyroidism or hyperthyroidism.