Lenvatinib: an investigational agent for the treatment of differentiated thyroid cancer

ABSTRACT

Introduction

Differentiated thyroid cancer (DTC; >90% of all TCs) derives from follicular cells. Surgery is the main therapeutic strategy, and radioiodine (RAI) is administered after thyroidectomy. When DTC progresses, it does not respond to RAI and thyroid-stimulating hormone (TSH)-suppressive thyroid hormone treatment, and other therapies (i.e. surgery, external beam radiation therapy and chemotherapy) do not lead to a better survival. Thanks to the understanding of the molecular pathways involved in TC progression, important advances have been done. Lenvatinib is a multitargeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRα, RET, and KIT signaling networks implicated in tumor angiogenesis, approved in locally recurrent or metastatic, progressive, RAI-refractory DTC. Unmet needs regarding the patient clinical therapy responsiveness in aggressive RAI-refractory DTC still remain.

Areas covered

We provide an overview from the literature of in vitro, in vivo and real-life studies regarding lenvatinib as an investigational agent for the treatment of aggressive TC.

Expert opinion

According to the SELECT trial, the treatment should be initiated with a dosage of 24 mg/day, subsequently decreasing it in relation to the side effects. The decision making process in patients with aggressive RAI-refractory DTC should be personalized and the potential toxicity should be properly managed.

KEYWORDS:

• Aggressive radioiodine-refractory differentiated thyroid cancer
• lenvatinib
• thyroid cancer
• tyrosine kinase inhibitors

Article highlights

• When DTC progresses, it does not respond to RAI and TSH-suppressive thyroid hormone treatment, and other therapies (i.e. surgery, external beam radiation therapy and chemotherapy) do not lead to a better survival. Thanks to the understanding of the molecular pathways involved in TC progression, important advances have been done for the therapy

• Lenvatinib is a multitargeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRα, RET, and KIT signaling networks implicated in tumor angiogenesis, approved in locally recurrent or metastatic, progressive, RAI-refractory DTC

• According to the results deriving from the SELECT trial, the treatment with lenvatinib should be initiated with a dosage of 24 mg/die, subsequently decreasing the dose in relation to the side effects

• AE of any grade can occur in >40% of patients receiving lenvatinib, including hypertension, asthenia or fatigue, nausea, decreased appetite, proteinuria, diarrhea, decreased weight, palmar-plantar erythrodysesthesia

• The decision making process in patients with aggressive RAI-refractory DTC should be personalized and the potential toxicity should be evaluated and properly managed

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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 paper was not funded.