Sorafenib in Metastatic Thyroid Cancer: A Systematic Review

Disclosures of potential conflicts of interest may be found at the end of this article. Key Words. Tyrosine kinase inhibitors x Chemotherapy x Response rate x Adverse effects Background. Sorafenib was recently approved by the U.S. Food and Drug Administration for radioiodine-resistant metastatic differentiated thyroid cancer (DTC). In addition, two drugs (vandetanib and cabozantinib) have received U.S. Food and Drug Administration approval for use in medullary thyroid cancer (MTC). Several published phase II trials have investigated the efficacy of sorafenib in thyroid cancers, but to date, results from those studies have not been compared. Methods. A systematic reviewof the literaturewas performed to assess response rate, median progression-free survival, and adverse events associatedwith sorafenib therapy formetastatic thyroid cancers. Results. This review includedseventrials involving219patients: 159 with DTC (papillary, follicular, and poorly differentiated), 52 with MTC, and 8 with anaplastic thyroid cancer. No study reported complete responses to treatment. Overall partial response, stable disease, and progressive disease rates were 21%, 60%, and 20%, respectively. The median progression-free survival was 18 months for patients with all subtypes of thyroid cancer. Drug was discontinued in 16 % of patients because of toxicities or intolerance, and the dose was reduced in a further 56%. Side effects with an incidence $50 % were hand-foot syndrome (74%), diarrhea (70%), skin rash (67%), fatigue (61%), andweight loss (57%). Deaths not related to progressive disease occurred in nearly 4 % of patients. Conclusion.Treatment with sorafenib in patients with pro-gressive DTC andMTC is a promising strategy, but the adverse event rate is high, leading to a high rate of dose reduction or discontinuation. Consequently, sorafenib use in patients with metastatic thyroidcancer requires careful selectionofpatients and careful management of side effects.The Oncologist 2014