Advances in small molecule therapy for treating metastatic thyroid cancer

ABSTRACT

Introduction: Multi kinase inhibitors (MKIs) are new drugs, which show activity against receptors of different growth factors leading to the inhibition of tumor cells growth and proliferation. This review summarizes a 10-year experience with the use of MKIs in thyroid cancer (TC). It focuses not only on sorafenib, lenvatinib, vandetanib and cabozantinib, already approved in TC, but also presents an overview of the results of different trials with distinct MKIs so far carried out in TC.

Areas covered: Published results of phase I, II and III studies and other reports evaluated the efficacy of different targeted drugs in TC.

Expert opinion: Despite numerous clinical trials with distinct MKIs, only four of them unequivocally demonstrated a beneficial effect on progression free survival in radioiodine refractory differentiated or medullary TC. In contrast to other solid tumors, we are still lacking in convincing evidences of their impact on overall survival. We still do not have any strong proof fulfilling evidence-based medicine criteria, when to start MKIs and which drug to use. The questions whether we really have to wait for disease progression in patients with a large tumor burden and/or aggressive types TC or when to stop MKIs treatment remain open.

KEYWORDS:

• Tyrosine kinase inhibitors
• multikinase inhibitors
• sorafenib
• lenvatinib
• vandetanib
• cabozantinib
• differentiated
• medullary
• anaplastic thyroid cancer

Article highlights

• To date four MKIs unequivocally demonstrated a beneficial effect on PFS in RAI-refractory DTC (sorafenib and lenvatinib) and MTC (vandetanib and cabozantinib).

• So far there are no convincing proofs of the impact of MKIs therapy on OS in RAI-refractory DTC and MTC

• The attempts of the use of distinct MKIs in ATC were not successful

• The most common MKI-related complications are: diarrhea, different gastrointestinal disturbances, skin reactions, mucositis, fatigue, and weight loss. However, some rare adverse reactions such as: bleeding, pulmonary embolism, arterial and venous thrombosis, heart failure, QTC prolongation, gastrointestinal perforation or fistula formation, may be life threatening or even in single cases cause a death.

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Declaration of interest

J Krajewska has participated in a Bayer HealthCare Pharmaceuticals Advisory Board. J Jarzab has participated in AstraZeneca and Sobi Advisory Boards and has received honoraria from Sanofi, Ipsen, Novartis, Amgen, Bayer HealthCare Pharmaceuticals, Pfizer, Roche, Eisai, Oxigene and Exelixis. 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.

Additional information

Funding

The article was supported by the Polish National Center for Research and Development MILESTONE project – Molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant no. STRATEGMED 2/267398/4/NCBR/2015.