FGFR inhibitors for advanced cholangiocarcinoma
Mené sur 146 patients atteints d’un cholangiocarcinome de stade localement avancé ou métastatique réfractaire ou récidivant, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse objective, et la toxicité du pémigatinib (un inhibiteur de FGFR1, 2 et 3 dispensé par voie orale), selon la présence de fusions ou de réarrangements du gène FGFR2 (durée médiane de suivi : 17,8 mois)
The prognosis of advanced or metastatic cholangiocarcinoma is extremely unsatisfactory, mainly owing to few treatment options and poor responses to conventional chemotherapy regimens. Since 2007, advances in next-generation sequencing have substantially improved the ability to understand the complex molecular mechanisms underlying the progression of cholangiocarcinoma. The most promising target for cholangiocarcinoma identified in recent years is the fibroblast growth factor (FGF) signalling pathway, which consists of 22 human FGFs and four transmembrane receptor tyrosine kinases (FGF receptors [FGFRs] 1–4). Fusions, rearrangements, translocations, and amplifications of FGFR genes are closely related to the initiation and progression of some cancers. FGFR2 mutations have been identified in nearly 20% of all cholangiocarcinomas and targeting this kinase presents a novel and exciting therapeutic strategy against cholangiocarcinomas. Several FGFR-specific inhibitors are being assessed in clinical trials for FGFR-mutant cholangiocarcinomas, including non-selective and selective FGFR inhibitors
The Lancet Oncology , commentaire, 2019