Treatment of Unresectable or Metastatic Extrahepatic Cholangiocarcinoma with Targetable Molecular Alterations

This protocol addresses first-line management of extrahepatic cholangiocarcinoma (eCCA) in patients with unresectable or metastatic disease who carry a targetable molecular alteration identified on molecular profiling.

Clinical scenario Unresectable or metastatic extrahepatic cholangiocarcinoma with a targetable molecular alteration on molecular profiling, including:

FGFR2 fusion or rearrangement
IDH1 R132 mutation
BRAF V600E mutation
HER2/ERBB2 positivity
NTRK fusion
RET fusion

Treatment approach (partial) First-line management involves combination systemic therapy, with molecular profiling integral to identifying actionable alterations that may guide further targeted intervention — the complete regimen and algorithm are detailed in the full protocol.

Instant Access to Structured Evidence-Based Regimens

References

Gemcitabine and cisplatin in combination with either durvalumab or pembrolizumab should be considered standard of care for the first-line systemic treatment of patients with unresectable or metastatic eCCA (LoE 2, strong recommendation, consensus).

Patients with unresectable or metastatic eCCA should receive molecular profiling to identify and therapeutically address actionable alterations and to support inclusion into clinical trials (LoE 2, strong recommendation, strong consensus).

DOI: 10.1016/j.jhep.2025.03.007

View source ↗