Background: Cholangiocarcinoma (CCA) is a diverse group of aggressive liver tumors with up to 20% being intrahepatic CCA (iCCA). Up to 15% of patients with iCCA have fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements. Here we evaluated iCCA treatment with pemigatinib, a selective inhibitor of FGFR1-3, in two patients from Denmark and Finland.

Patients: We identified a total of two Nordic patients with iCCA in our clinics, who received first-line cisplatin/gemcitabine before initiating pemigatinib.

Results: Case 1 was a 34-year-old woman with aggressive, metastatic iCCA upon presentation, who progressed on cisplatin/gemcitabine. Pemigatinib was initiated after FGFR2 fusion detection by genomic testing. She had a partial response after three cycles (9 weeks) of pemigatinib but experienced disease progression after three more pemigatinib cycles. Adverse events were primarily managed by supportive care and dose reduction, except hyperphosphatemia, which was complicated by food allergies and required medication. She received subsequent chemotherapy but deteriorated rapidly and died 1 month later. Case 2 was an 81-year-old man with unresectable iCCA who achieved stable disease with first-line chemotherapy. He switched to pemigatinib after FGFR2 fusion detection by next-generation sequencing. The tumor shrank by 20% after three pemigatinib cycles and completely calcified with continued treatment. Adverse events were managed by two dose adjustments. Treatment has continued for 57 months and is ongoing.

Interpretation: CCA is an aggressive disease that requires early molecular testing of abundant biopsy tissue so not to delay second-line therapies, such as pemigatinib. Variability in treatment outcomes is expected.