Pemigatinib for patients with previously treated, locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements: A joint analysis of the French PEMI-BIL and Italian PEMI-REAL cohort studies

Eur J Cancer. 2024 Mar:200:113587. doi: 10.1016/j.ejca.2024.113587. Epub 2024 Feb 6.

Abstract

Background: Pemigatinib is approved for patients with pretreated, locally advanced or metastatic CCA harboring FGFR2 rearrangements or fusions. We aim to assess the effectiveness and safety of pemigatinib in real-world setting.

Material and methods: A joint analysis of two multicentre observational retrospective cohort studies independently conducted in France and Italy was performed. All consecutive FGFR2-positive patients affected by CCA and treated with pemigatinib as second- or further line of systemic treatment in clinical practice, within or outside the European Expanded Access Program, were included.

Results: Between July 2020 and September 2022, 72 patients were treated with pemigatinib in 14 Italian and 25 French Centres. Patients had a median age of 57 years, 76% were female, 81% had ECOG-PS 0-1, 99% had intrahepatic CCA, 74% had ≥ 2 metastatic sites, 67% had metastatic disease at diagnosis, while 38.8% received ≥ 2 previous lines of systemic treatment. At data cut-off analysis (April 2023), ORR and DCR were 45.8% and 84.7%, respectively. Median DoR was 7 months (IQR: 5.8-9.3). Over a median follow-up time of 19.5 months, median PFS and 1-year PFS rate were 8.7 months and 32.8%. Median OS and 1-year OS rate were 17.1 months and 60.6%. Fatigue (69.4%), ocular toxicity (68%), nail toxicities (61.1%), dermatologic toxicity (41.6%) hyperphosphataemia (55.6%), stomatitis (48.6%), and diarrhea (36.1%) were the most frequent, mainly G1-G2 AEs. Overall incidence of G3 AEs was 22.2%, while no patient experienced G4 AE. Dose reduction and temporary discontinuation were needed in 33.3% and 40.3% of cases, with 1 permanent discontinuation due to AEs.

Conclusions: These results confirm the effectiveness and safety of pemigatinib in a real-world setting.

Keywords: BTC; FGFR2 fusions/rearrangements; Intrahepatic cholangiocarcinoma; Real-world data; Systemic treatment; Targeted therapy.

MeSH terms

  • Bile Duct Neoplasms* / drug therapy
  • Bile Duct Neoplasms* / genetics
  • Bile Duct Neoplasms* / pathology
  • Bile Ducts, Intrahepatic / pathology
  • Cholangiocarcinoma* / drug therapy
  • Cholangiocarcinoma* / genetics
  • Cholangiocarcinoma* / pathology
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Morpholines*
  • Pyrimidines*
  • Pyrroles*
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Retrospective Studies

Substances

  • pemigatinib
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2
  • Morpholines
  • Pyrimidines
  • Pyrroles