Systemic Therapy for Advanced Metastatic Thyroid Cancer

Abstract

Thyroid cancer is the most common form of endocrine malignancy worldwide, and differentiated thyroid cancer (DTC) is the most common histological subtype and includes papillary, follicular, and Hurthle cell histologies. The incidence of thyroid cancer is increasing among both men and women, with a projected 62,450 new cases in 2015. Treatment for DTC is typically surgical, followed by radioactive iodine and levothyroxine therapy. However, a minority of patients with DTC will develop metastatic disease, and as many as two-thirds of these patients will be refractory to iodine therapy. Cytotoxic chemotherapy has extremely limited activity in metastatic, iodine-refractory cases of DTC. Over the past decade, the discovery of specific genetic mutations associated with DTC, along with the development of novel agents such as multitargeted tyrosine kinase inhibitors (MKI), has led to FDA approval of new therapeutic agents in metastatic, radioiodine-refractory DTC. This incredible progress represents a major breakthrough in the field of DTC treatment. Despite these exciting advances the impact of such therapies on overall survival remains unknown. Further research is needed to identify new therapies with better response and toxicity profiles as well as to determine how to best utilize these new agents safely either sequentially or in combination and what steps to take when they are no longer effective.