Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer

Semin Oncol. 2019 Feb;46(1):57-64. doi: 10.1053/j.seminoncol.2018.11.004. Epub 2018 Dec 21.

Abstract

Lenvatinib is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor receptors 1-4, RET, KIT, and platelet-derived growth factor receptor-α. Lenvatinib is approved as a monotherapy for the treatment of radioiodine-refractory differentiated thyroid cancer and in combination with everolimus for the second-line treatment of advanced renal cell carcinoma. Lenvatinib is also under investigation for the treatment of several malignancies including unresectable hepatocellular carcinoma. Although lenvatinib is associated with favorable efficacy, it is associated with adverse events (AEs) that the clinician will have to closely monitor for and proactively manage. Most of these AEs are known class effects of VEGF-targeted therapies, including hypertension, diarrhea, fatigue or asthenia, decreased appetite, and weight loss. This review summarizes the safety profile of lenvatinib and offers guidance for the management of both frequent and rare AEs. We discuss the potential mechanisms underlying these AEs and present practical recommendations for managing toxicities. The development of treatment plans that include prophylactic and therapeutic strategies for the management of lenvatinib-associated AEs has the potential to improve patient quality of life, optimize adherence, minimize the need for dose reductions, treatment interruptions, or discontinuations, and maximize patient outcomes.

Keywords: Adverse event; Differentiated thyroid cancer; Lenvatinib; Side effect; Tyrosine kinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / epidemiology
  • Carcinoma, Renal Cell / pathology
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Everolimus / adverse effects
  • Everolimus / therapeutic use
  • Humans
  • Iodine Radioisotopes / therapeutic use*
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / pathology
  • Phenylurea Compounds / adverse effects*
  • Phenylurea Compounds / therapeutic use
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Quinolines / adverse effects*
  • Quinolines / therapeutic use
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / epidemiology

Substances

  • Iodine Radioisotopes
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Quinolines
  • Everolimus
  • lenvatinib