Lenvatinib is an oral tyrosine kinase inhibitor (RTK) that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3. The drug also inhibits other proangiogenic and oncogenic pathway-related RTKs including fibroblast growth factor receptors 1-4 and platelet derived growth factor α, KIT and RET.
The SELECT study (n=392) was a phase III randomised controlled study designed to assess the safety and efficacy of lenvatinib in patients with differentiated thyroid cancer unresponsive to radioactive iodine and with radiographic evidence of progression within the previous 12 months.
Participants were randomised to receive lenvatinib (24mg once daily, n=261) or placebo (n=131) in 28-day cycles.
Median progression-free survival was significantly higher in the lenvatinib group than in the placebo group (18.3 months vs 3.6 months, p<0.0001). The positive effect on progression-free survival was observed across sub-groups of age (above or below 65 years), sex, race, histological subtype, geographic region and those who had received 0 or 1 prior VEGF/VEGF-targeted therapy.
The objective response rate was also significantly higher in the lenvatinib group (64.8%: 4 complete responses, 165 partial responses) than in the placebo group (1.5%: 0 complete responses, 2 partial responses) (p<0.0001).
Adverse reactions occurred more frequently with lenvatinib than with placebo. The most commonly reported adverse effects, occurring in more than 40% of patients in the lenvatinib group, included hypertension, diarrhoea, anorexia, weight loss, fatigue and nausea.