Expression of fibroblast growth factor receptor 4 and clinical response to lenvatinib in patients with anaplastic thyroid carcinoma: a pilot study

Eur J Clin Pharmacol. 2020 May;76(5):703-709. doi: 10.1007/s00228-020-02842-y. Epub 2020 Feb 7.

Abstract

Purpose: Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC).

Methods: We investigated FGFR4 expression in patients with ATC and analyzed their clinical responses to lenvatinib. Primary tumor samples were obtained from 12 patients with ATC who underwent surgery or core needle biopsy. FGFR4 protein expression in all ATC samples was analyzed via immunohistochemistry, and the treatment efficacy of lenvatinib was evaluated.

Results: The proportion of FGFR4-positive cells in the samples ranged from 0 to 50%. Four patients had partial responses, and three patients had stable diseases as a best clinical response to lenvatinib. The median PFS durations of patients with none, weak, and moderate intensity were 0.5, 3.2 (95% CI 1.1-not estimable [NE]), and 4.6 (95% CI 1.1-NE) months, respectively (p = 0.003).

Conclusions: Because FGFR4 was expressed in ATC tissues, the FGFR4 expression might be associated with the treatment efficacy of lenvatinib in a part of ATC patients. To clarify whether FGFR4 can serve as a prognostic or predictive factor for lenvatinib therapy, more cases must be accumulated.

Keywords: Clinical research; Fibroblast growth factor receptor; Lenvatinib; Molecular biology; Thyroid cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenylurea Compounds / therapeutic use*
  • Pilot Projects
  • Quinolines / therapeutic use*
  • Receptor, Fibroblast Growth Factor, Type 4 / drug effects*
  • Receptor, Fibroblast Growth Factor, Type 4 / metabolism
  • Thyroid Carcinoma, Anaplastic / drug therapy*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Quinolines
  • FGFR4 protein, human
  • Receptor, Fibroblast Growth Factor, Type 4
  • lenvatinib