title: 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.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: mcabani@mdanderson.org.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cabanillas
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: MAHabra@mdanderson.org.
authors.forename: Mouhammed Amir
authors.initials: MA
authors.lastname: Habra
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000628:therapy; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D000068338:Everolimus / Q000008:administration & dosage; D006801:Humans; D007223:Infant; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D051379:Mice; D058990:Molecular Targeted Therapy; D015337:Multicenter Studies as Topic; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D017239:Paclitaxel / Q000008:administration & dosage; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000628:therapy; D013965:Thyroidectomy; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D017978:Receptors, Growth Factor; D000068338:Everolimus; D016190:Carboplatin; C531958:lenvatinib; D017239:Paclitaxel
keywords: Advanced; Differentiated; Medullary; Multikinase; Refractory; Survival