Treatment of Advanced Biliary Tract Cancer: ASCO Living Guideline, Version 2026.1.0

PURPOSE This living guideline provides recommendations for liquid biopsy and treatment of patients with advanced biliary tract cancer . METHODS The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for liquid biopsy and systemic therapy for patients with advanced biliary tract cancer. RESULTS Six studies provided estimates of concordance between liquid biopsy and tissue biopsy. Nine RCTs were included in the evidence base for first-line therapy. One phase III RCT and four phase II RCTs were included in the evidence for second-line chemotherapy. Eleven single studies or reviews supported biomarker-specific second-line therapy recommendations. RECOMMENDATIONS Testing with broad-based tissue DNA and RNA NGS testing to determine the presence of targetable biomarkers is recommended at the time of diagnosis at any stage. Liquid biopsy with plasma is generally recommended only when tissue biopsy is unavailable. As first-line therapy for patients with pMMR/MSS advanced BTC, immune checkpoint inhibitors (ICIs) plus chemotherapy is recommended. Options for patients with advanced BTC who are not candidates for ICIs are included in the guideline. Pembrolizumab monotherapy is an option for patients with dMMR/MSI-H advanced BTC. For patients with disease progression on first-line treatment and who have no identified biomarkers, FOLFOX with active symptom control, or active symptom control alone are recommended; options for patients who are ineligible for oxaliplatin-based chemotherapy are included in the guideline. Second-line therapy options are recommended for patients with dMMR/MSI-H, IDH1 mutations, FGFR2 fusions or rearrangements, BRAF V600E mutations, HER2 overexpression, RET, NTRK1/2/3, or NRG1 fusions. Additional information is available at https://ascopubs.org/guidelines/living-guidelines