Drug Evaluation

Lenvatinib: a new option for the treatment of advanced iodine refractory differentiated thyroid cancer?

Loredana Lorusso

The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK

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Kate Newbold

*Author for correspondence:

E-mail Address: Kate.newbold@rmh.nhs.uk

The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK

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Published Online:15 Jun 2015https://doi.org/10.2217/fon.15.68

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Abstract

ABSTRACT

Lenvatinib mesylate (E7080; 4-[3-chloro-4-(N′-cyclopropylureido) phenoxy] 7-methoxyquinoline-6-carboxamide mesylate) is an oral molecule that inhibits multiple tyrosine kinase receptors such as VEGF-R-1–3, FGF-R-1–4, RET, c-KIT and PDGF-R-β. Phase I studies identified the maximum tolerated dose to be 25 mg daily that, in fasting treated patients, is rapidly absorbed with maximum concentrations achieved within 3 h of administration. In these studies, lenvatinib showed activity in solid tumors. Subsequently, Phase II studies in thyroid cancer, in particular differentiated thyroid cancer (DTC), confirmed good clinically significant activity and the recently published Phase III SELECT trial reported median progression-free survival was 18.3 months with lenvatinib versus 3.6 months with placebo (hazard ratio for progression or death: 0.21; 99% CI: 0.14–0.31; p < 0.001). Treatment-related adverse effects occurred in more than 40% of patients on lenvatinib. These were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%) and nausea (in 41.0%). Discontinuations of lenvatinib because of adverse effects occurred in 37 patients (14.2%) compared with three patients who received placebo (2.3%). Six of 20 deaths in patients on lenvatinib were considered to be drug-related. Lenvatinib has been licensed by the US FDA and EMA based on these data and provides an option for the treatment of radioiodine refractory DTC.

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Published online 15 June 2015

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Financial & competing interests disclosure

Kate Newbold has had advisory roles with and received honoraria from Eisai, Astra Zeneca and Genzyme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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