Advances in small molecule therapy for treating metastatic thyroid cancer.

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.