Second-Line Systemic Therapy for Unresectable or Metastatic Extrahepatic Cholangiocarcinoma With No Targetable Molecular Alteration
When unresectable or metastatic extrahepatic cholangiocarcinoma (eCCA) advances and molecular profiling reveals no targetable alteration, the clinical pathway narrows to specific second-line systemic chemotherapy options supported by evidence.
Clinical Scenario
This protocol addresses patients with unresectable or metastatic extrahepatic cholangiocarcinoma in whom comprehensive molecular profiling has identified no targetable molecular alteration, making tumour-agnostic targeted approaches unavailable. These patients represent a distinct subset requiring a defined systemic chemotherapy strategy.
Systemic Therapy Approach
Second-line systemic chemotherapy is indicated in this setting. The evidence-based regimen includes FOLFOX as the primary supported option — with additional chemotherapy alternatives available depending on patient factors. The complete regimen selection, sequencing guidance, and clinical decision criteria are in the full protocol.
References
DOI: 10.1016/j.jhep.2025.03.007In the absence of targetable alterations, FOLFOX should be offered as a subsequent line of systemic therapy for patients diagnosed with advanced eCCA who have tumour progression on first-line therapy. Alternatives to consider include irinotecan-based options (based on phase II trial data) (LoE 2, strong recommendation, consensus).
Upon progression to first-line chemotherapy, second-line chemotherapy options for biliary tract tumours include FOLFOX and liposomal irinotecan and 5-fluorouracil (NalIRI+5FU).
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