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Lenvatinib: A Review in Refractory Thyroid Cancer

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Abstract

Lenvatinib (Lenvima®) is an oral, multi-targeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, fibroblast growth factor receptors 1, 2, 3 and 4, platelet-derived growth factor receptor alpha, and RET and KIT signalling networks, which are implicated in tumour growth and maintenance. In the EU and USA, lenvatinib is indicated for the treatment of locally recurrent or metastatic progressive, radioiodine-refractory differentiated thyroid cancer (RR-DTC). This approval was based on the results of the randomized, double-blind, multinational, phase 3 SELECT study, in which lenvatinib significantly improved median progression-free survival (PFS) and overall response rate compared with placebo in patients with RR-DTC. The PFS benefit with lenvatinib was seen in all pre-specified subgroups, including patients who had received either one or no prior VEGF-targeted therapy. Moreover, the PFS benefit with lenvatinib was maintained regardless of BRAF or RAS mutation status. The safety and tolerability profile of lenvatinib in SELECT was consistent with that of other VEGF/VEGF receptor-targeted therapies and was mostly manageable. Hypertension was the most common treatment-related adverse event in lenvatinib-treated patients, but only infrequently led to discontinuation of the drug. Although not collected in SELECT, information on quality of life would be useful in assessing the overall impact of therapy on the patient. This notwithstanding, the data which are available indicate that lenvatinib is an effective and generally well-tolerated treatment option for patients with RR-DTC. Lenvatinib, therefore, offers an acceptable alternative to sorafenib — currently, the only other TKI approved for this indication.

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Acknowledgments

During the peer review process, the manufacturer of lenvatinib was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    James E. Frampton

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  1. James E. Frampton
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Correspondence to James E. Frampton.

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The preparation of this review was not supported by any external funding.

Conflicts of Interest

James Frampton is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: A. Antonelli, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; C. Perez, Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA; J Sáez, Endocrinology and Nutrition Service, University Hospital of Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.

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Frampton, J.E. Lenvatinib: A Review in Refractory Thyroid Cancer. Targ Oncol 11, 115–122 (2016). https://doi.org/10.1007/s11523-015-0416-3

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