M Hegazi, A Azadi, D. Jain, R. O. Redman, César Augusto Pérez
After the pathogenesis of thyroid carcinomas was better understood and the role of molecular alterations in RET, BRAF and RET/PTC rearrangement was revealed, several trials using multikinase inhibitors were developed during the last decade for the treatment of recurrent radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), achieving a remarkable success. Sorafenib became the first drug approved for this indication in more than two decades after a significant improvement in the progression-free survival was demonstrated. Lenvatinib (E-7080), an orally active inhibitor of multiple receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR) 1, 2 and 3, proto-oncogene tyrosine-protein kinase receptor Ret and mast/stem cell growth factor receptor Kit, yielded highly promising early clinical data, even when given after progression on first-line therapy. The phase III SELECT trial recently demonstrated the impressive clinical activity of the drug in RAI-refractory thyroid cancer, leading to the drug's approval by the regulatory agencies and potentially making lenvatinib the most effective drug available to date for the treatment of the disease.
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