Lenvatinib: Role in thyroid cancer and other solid tumors

Cancer Treat Rev. 2016 Jan;42:47-55. doi: 10.1016/j.ctrv.2015.11.003. Epub 2015 Dec 2.

Abstract

Despite recent breakthroughs in treatment of advanced thyroid cancers, prognoses remain poor. Treatment of advanced, progressive disease remains challenging, with limited treatment options. Small-molecule tyrosine kinase inhibitors, including vandetanib, cabozantinib, sorafenib, and lenvatinib, which are now FDA-approved for thyroid cancer, have shown clinical benefit in advanced thyroid cancer. Lenvatinib is approved for treatment of locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). It has been studied in phase II and III trials for treatment of advanced RAI-refractory DTC, and in a phase II trial for medullary thyroid cancer (MTC). Lenvatinib targets vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR-1-4), RET, c-kit, and platelet-derived growth factor receptor α (PDGFRα). Its antitumor activity may be due to antiangiogenic properties and direct antitumor effects. Lenvatinib has demonstrated antitumor activity in a variety of solid tumors, including MTC, in phase I and II clinical trials. In a phase II study in advanced RAI-refractory DTC, lenvatinib-treated patients achieved a 50% response rate (RR), with median progression-free survival (PFS) of 12.6 months. In a phase III trial in RAI-refractory DTC, median PFS in lenvatinib-treated patients was 18.3 months, with a 65% overall RR, versus 3.6 months in placebo-treated patients, with a 2% RR. Adverse events occurring in >50% of patients included hypertension, diarrhea, fatigue/asthenia, and decreased appetite. Lenvatinib is a promising new agent for treatment of patients with advanced thyroid cancer.

Keywords: Advanced; Differentiated; Medullary; Multikinase; Refractory; Survival.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carboplatin / administration & dosage
  • Carcinoma / drug therapy*
  • Carcinoma / enzymology
  • Carcinoma / therapy
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Everolimus / administration & dosage
  • Humans
  • Infant
  • Iodine Radioisotopes / therapeutic use
  • Mice
  • Molecular Targeted Therapy*
  • Multicenter Studies as Topic
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Paclitaxel / administration & dosage
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / pharmacology
  • Phenylurea Compounds / therapeutic use*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinolines / administration & dosage
  • Quinolines / adverse effects
  • Quinolines / pharmacology
  • Quinolines / therapeutic use*
  • Receptors, Growth Factor / antagonists & inhibitors
  • Signal Transduction / drug effects
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / enzymology
  • Thyroid Neoplasms / therapy
  • Thyroidectomy
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Iodine Radioisotopes
  • Neoplasm Proteins
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Quinolines
  • Receptors, Growth Factor
  • Everolimus
  • Carboplatin
  • lenvatinib
  • Paclitaxel