Lenvatinib: Role in thyroid cancer and other solid tumors. (January 2016)

• Record Type: Journal Article
• Authors: Cabanillas, Maria E.; Habra, Mouhammed Amir
• Is Part Of: Cancer treatment reviews. Volume 42(2016)
• Page Start: 47
• Page End: 55
• Publication Date: 2016-01
• Subjects: Refractory -- Differentiated -- Multikinase -- Medullary -- Survival -- Advanced; Cancer -- Periodicals; Cancer -- Treatment -- Periodicals; Neoplasms -- therapy -- Periodicals; Cancer -- Périodiques; Cancer -- Traitement -- Périodiques; Cancer -- Treatment; Electronic journals; Periodicals; 616.99406
• DOI: 10.1016/j.ctrv.2015.11.003
• Languages: English
• ISSNs: 0305-7372

Abstract

Highlights: We review advanced thyroid cancer (TC) etiology and signaling pathway mutations. We review the mechanism of action and role of tyrosine kinase inhibitors (TKIs). Lenvatinib, a multitargeted TKI, has broad antitumor and antiangiogenic activity. We review phase III radioactive iodine-refractory differentiated TC results. Lenvatinib shows superior progression-free survival and overall response rate. 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.