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A new promising oncogenic target (p.C382R) for treatment with pemigatinib in patients with cholangiocarcinoma

  • Point mutations of the fibroblast growth factor receptor (FGFR)2 receptor in intrahepatic cholangiocarcinoma (iCC) are mainly of unknown functional significance compared to FGFR2 fusions. Pemigatinib, a tyrosine kinase inhibitor, is approved for the treatment of cholangiocarcinoma with FGFR2 fusion/rearrangement. Although it is hypothesized that FGFR2 mutations may cause uncontrolled activation of the signaling pathway, the data for targeted therapies for FGFR2 mutations remain unclear. In vitro analyses demonstrated the importance of the p.C382R mutation for ligand-independent constitutive activation of FGFR2 with transforming potential. The following report describes the clinical case of a patient diagnosed with an iCC carrying a FGFR2 p.C382R point mutation which was detected in liquid, as well as in tissue-based biopsies. The patient was treated with pemigatinib, resulting in a sustained complete functional remission in fluorodeoxyglucose-positron emission tomography/computed tomography over 10 months to date. The reported case is the first description of a complete functional remission under the treatment with pemigatinib in a patient with p.C383R mutation.

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Author:Louisa Hempel, Constantin Lapa, Alexander Dierks, Andreas Gaumann, Josef Scheiber, Julia Veloso de Oliveira, Patrick Philipp, Cristina Oyarzun Laura, Stefan Wesarg, Sebastian Robert, Dirk Hempel
DOI:https://doi.org/10.1177/17588359221125096
Parent Title (English):Therapeutic Advances in Medical Oncology
Document Type:Article (peer reviewed)
Language:English
Publication Year:2022
Volume:14
faculties / departments:Fakultät für Angewandte Gesundheits- und Sozialwissenschaften