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Abstract
Sorafenib has been evaluated in several Phase II and III studies in patients with locally advanced/metastatic radioactive iodine–refractory differentiated thyroid carcinomas (DTCs), reporting partial responses, stabilization of the disease and improvement of progression-free survival. Best responses were observed in lung metastases and minimal responses in bone lesions. On the basis of these studies, sorafenib was approved for the treatment of metastatic DTC in November 2013. Few studies suggested that reduction of thyroglobulin levels, or of average standardized uptake value at the fluorodeoxyglucose-PET, could be helpful for the identification of responding patients; but further studies are needed to confirm these results. Tumor genetic marker levels did not have any prognostic or predictive role in DTC patients.The most common adverse events observed included skin toxicity and gastrointestinal and constitutional symptoms. Encouraging results have also been observed in patients with medullary thyroid cancer. Many studies are ongoing to evaluate the long-term efficacy and tolerability of sorafenib in DTC patients.
Financial and competing interests disclosure
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.
No writing assistance was utilized in the production of this manuscript.
Sorafenib (Nexavar®) is a small molecular (a bi-aryl urea) multi-targeted tyrosine kinase inhibitor, demonstrating inhibitory activity against VEGF receptor-2 and -3, c-Kit, PDGF receptor, RET/PTC and Raf kinases (more avidly C-Raf than B-Raf), and it is able to target the Raf/Mek/Erk pathway (MAPK pathway). In addition, sorafenib has also been shown to induce apoptosis through down-regulation of Mcl-1 in many cancer types.
Sorafenib was initially approved for the treatment of primary kidney cancer and advanced primary liver cancer.
Sorafenib has been evaluated in several Phase II and III studies in patients with locally advanced/metastatic radioactive iodine–refractory differentiated thyroid carcinoma (DTC), with reports of partial responses, stabilization of the disease and improvement of progression free survival.
Best responses were observed in lymph node and lung metastases, and minimal response in bone lesions.
Commonest adverse events include skin toxicity, gastrointestinal and constitutional symptoms.
Sorafenib was approved for the treatment of metastatic DTC in November 2013.
Some studies suggested that reduction of thyroglobulin levels, or of average standardized uptake value in the fluorodeoxyglucose-PET, could be helpful for the identification of responding patients, but further studies are needed to confirm these results.
Attempts have been made to personalize sorafenib therapy in each patient with DTC, on the basis of the molecular characterization of the tumor and the host factors.
Promising results have been also obtained in patients with MTC, reporting partial responses, stabilization of the disease and improvement of progression-free survival.
Treatment with sorafenib in thyroid cancer patients might lead to drug resistance that could arise from the activation of alternate mitogenic signals. Hence, the combination with other drugs or with different tyrosine kinase inhibitors has been recently proposed.