Fibroblast growth factor receptor (FGFR) inhibitors: A review of a novel therapeutic class

J Oncol Pharm Pract. 2021 Apr;27(3):702-710. doi: 10.1177/1078155220983425. Epub 2020 Dec 29.

Abstract

Comprehensive genomic profiling has an emerging role in cancer therapeutics. As treatment options remain needed for advanced cancers, patients are relying increasingly more on tumor genomic alterations as possible targets for cancer treatment. Frequent tumor fibroblast growth factor receptor (FGFR) alterations are seen in many cancers, and include genetic amplifications, mutations, rearrangements and fusions. FGFR inhibitors target these receptor alterations and show promise as a drug class. Currently 2 medications are currently FDA approved: erdafitinib and pemigatinib. Through the FDA accelerated approval process, erdafitinib is indicated to treat metastatic urothelial carcinoma with FGFR2 and FGFR3 alterations, whereas pemigatinib is indicated to treat unresectable cholangiocarcinoma with FGFR2 alterations. Despite growing knowledge about such advanced cancers, treatment is usually palliative. With multiple FGFR inhibitors in the pipeline, further FDA approvals are possible, and it is likely their role in therapy will extend to other cancer types. This review outlines erdafitinib, pemigatinib, their role in cancer, as well as outlining the possible future use of other FGFR inhibitors in urothelial carcinoma, cholangiocarcinoma, and other malignancies.

Keywords: FGFR; erdafitinib; fibroblast growth factor receptor; pemigatinib.

Publication types

  • Review

MeSH terms

  • Bile Duct Neoplasms / drug therapy
  • Bile Duct Neoplasms / metabolism
  • Carcinoma, Transitional Cell / drug therapy
  • Carcinoma, Transitional Cell / metabolism
  • Cholangiocarcinoma / drug therapy
  • Cholangiocarcinoma / metabolism
  • Clinical Trials as Topic / methods
  • Humans
  • Morpholines / pharmacology
  • Morpholines / therapeutic use*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use*
  • Quinoxalines / pharmacology
  • Quinoxalines / therapeutic use*
  • Receptor, Fibroblast Growth Factor, Type 2 / antagonists & inhibitors*
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism
  • Receptor, Fibroblast Growth Factor, Type 3 / antagonists & inhibitors*
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism

Substances

  • Morpholines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • Pyrroles
  • Quinoxalines
  • erdafitinib
  • FGFR2 protein, human
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptor, Fibroblast Growth Factor, Type 3
  • pemigatinib