Lenvatinib for the treatment of radioiodine-refractory follicular and papillary thyroid cancer

Introduction: A new treatment opportunity for radioiodine-resistant differentiated thyroid cancer (DTC) has emerged during recent years as the key role of tyrosine kinases in the pathogenesis of thyroid carcinoma has been demonstrated. Lenvatinib [E7080] is an oral potent inhibitor of growth factor receptors, including VEGFR1/Flt-1, VEGFR2/KDR, VEGFR3, FGFR1,2,3,4, PDGFR-alpha, as well as RET and KIT signaling network. Areas covered: Lenvatinib activity against DTC has been demonstrated in clinical trials. In a Phase II study, partial response was achieved in 50% of patients. The response rates between subjects who received prior VEGFR-directed therapy and those with no prior VEGFR-directed therapy were 41 and 54%, respectively. In a Phase III, randomized, placebo-controlled study, median progression-free survival (PFS) in lenvatinib group was significantly longer than in the placebo group at 18.3 versus 3.6 months, respectively. This advantage was also noticed both in subjects with prior and without prior anti-VEGFR treatment; median PFS was 15.1 and 18.7 months, respectively. The most frequent lenvatinib-related side effects, observed in both studies, were hypertension, proteinuria, diarrhea, appetite decrease and weight loss. Although a lot of them were manageable, in most of the patients dose reduction was required. Expert opinion: Lenvatinib may constitute a new therapeutic option for advanced, radioiodine-refractory DTC.