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This algorithm sequences systemic therapy for advanced biliary tract cancer, combining a chemoimmunotherapy backbone with molecularly targeted options defined by tumor genotype.
The standard first-line regimen is gemcitabine and cisplatin plus durvalumab, supported by TOPAZ-1, the first positive immunotherapy trial in biliary tract cancer, which improved overall survival over gemcitabine and cisplatin alone. Gemcitabine and cisplatin plus pembrolizumab (KEYNOTE-966) is shown as an alternative. Molecular profiling identifies targeted options: pemigatinib or futibatinib for FGFR2 fusions, ivosidenib for IDH1 mutations (ClarIDHy), trastuzumab or trastuzumab deruxtecan for HER2-amplified tumors, and dabrafenib plus trametinib for BRAF-mutated disease (ROAR). In the second line, FOLFOX is the cytotoxic option, supported by ABC-06, which improved overall survival over active symptom control alone after progression on gemcitabine-based chemotherapy and provided the first randomized evidence for second-line treatment. A genotype-directed clinical trial should always be considered.
Background reading: Biliary Cancers board review notes.
Starting point: Advanced biliary tract cancer. Full background: Biliary Cancers notes.