Lenvatinib: Role in thyroid cancer and other solid tumors.

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.

• Authors: Maria E Cabanillas, Mouhammed Amir Habra
• Journal: Cancer treatment reviews (Cancer Treat Rev) Vol. 42 Pg. 47-55 (Jan 2016) ISSN: 1532-1967 [Electronic] Netherlands
• PMID: 26678514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

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

Topics

• Animals
• Antineoplastic Agents (adverse effects, pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma (drug therapy, enzymology, 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, enzymology)
• Paclitaxel (administration & dosage)
• Phenylurea Compounds (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Protein Kinase Inhibitors (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Quinolines (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Receptors, Growth Factor (antagonists & inhibitors)
• Signal Transduction (drug effects)
• Thyroid Neoplasms (drug therapy, enzymology, therapy)
• Thyroidectomy
• Xenograft Model Antitumor Assays