Lenvatinib for thyroid cancer treatment: discovery, pre-clinical development and clinical application

ABSTRACT

Introduction: About one third of patients affected with thyroid cancer present with recurrent disease. Unresectability, advanced disease and radioiodine refractoriness are considered poor prognostic factors. Treatment with small molecules inhibiting molecular signaling can be considered for patients with progressive disease, when other therapeutic strategies cannot be applied. Lenvatinib is a tyrosine kinase inhibitor targeting multiple molecular factors involved in angiogenesis and tumor progression. Preclinical studies have demonstrated the utility of lenvatinib as a targeted therapy for different tumors, including both differentiated and anaplastic thyroid cancer.

Areas covered: The authors provide an overview of the preclinical development of lenvatinib in the treatment of thyroid cancer and review its clinical application. They also provide their expert opinion on its development.

Expert opinion: Preclinical studies have helped in the understanding of the mechanisms of thyroid carcinogenesis and in the development of a targeted therapy. These findings have represented the rationale for the use of lenvatinib in clinical trials, which have confirmed its utility but yet failed to prove a clear benefit in overall survival. The decision to start a systemic treatment with lenvatinib must be personalized for each patient evaluating the risk/benefits ratio. Treatment emergent adverse events must be considered and reasonably managed by a multidisciplinary approach.

KEYWORDS:

• Lenvatinib
• thyroid cancer
• tyrosine kinase inhibitor
• preclinical studies

Article Highlights

• Radioiodine refractory differentiated thyroid cancer (RR-DTC) has a poor prognosis and there are few treatment options available

• Lenvatinib is potent oral tyrosine kinase inhibitor that targets VEGFR 1-3, FGFR 1-4, RET, mast/stem cell growth factor receptor kit (SCFR) or c-Kit, and PDGFRbeta

• Preclinical studies demonstrated the utility of lenvatinib as targeted therapy for different tumors including DTC

• On the basis of the positive results of the phase III trial SELECT, lenvatinib has been approved in 2015 by the Food and Drug Administration (FDA) and by the European Medical Agency (EMA) for the treatment of patients with locally recurrent or metastatic progressive RR-DTC

• Treatment-emergent adverse events are common and must be considered before treatment initiation and properly managed by a multidisciplinary approach

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.