Navigating Systemic Therapy in Advanced Thyroid Carcinoma

From Standard of Care to Personalized Therapy and Beyond

Sarika N. Rao; Maria E. Cabanillas


J Endo Soc. 2018;2(10):1109-1130. 

In This Article

Abstract and Introduction


Thyroid cancer, with the exception of anaplastic thyroid cancer, typically has very favorable outcomes with the standard therapy. However, those that persist, recur, or metastasize are associated with a worse prognosis. Targeted therapy with kinase inhibitors has shown promise in advanced cases of thyroid cancer, and currently five drug regimens are approved for use in clinical practice in the treatment of differentiated, medullary, and anaplastic thyroid cancer, with more options in the pipeline. However, one of the greatest dilemmas is when and how to initiate one of these drugs, and this is discussed herein.


Thyroid cancer is the most common endocrine malignancy, and its incidence continues to rise in the United States.[1] All thyroid cancers, except for medullary thyroid cancer (MTC), are derived from the follicular cells. Differentiated thyroid cancer (DTC) has three basic subtypes, papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), and Hurthle cell thyroid cancer (HCTC), and account for 95% of all thyroid cancers.[2] Poorly differentiated thyroid cancers (PDTCs) also fall into the category of DTC. Well-differentiated thyroid cancers generally have an indolent course, as these cells are structurally more similar to benign thyroid cells.[3] DTC is usually curable with surgery, selective use of radioactive iodine (131I) (RAI) ablation, and thyroid hormone suppressive therapy.[4]

Despite the rising incidence of DTC, <10% of cases will develop locally advanced or metastatic disease; ~67% of these advanced cases are radioiodine refractory (RAIR).[5] When metastases occur in DTC, further surgery or RAI ablation may be curative in a few patients, and a higher dose of thyroid hormone replacement slows the progression of disease.

MTC derives from malignant transformation of C cells (the parafollicular neuroendocrine cells adjacent to the follicular cells within the thyroid) and accounts for ~4% of all thyroid cancers.[2] It is primarily treated with surgery. In metastatic or recurrent MTC, surgery and/or other localized therapies, such as liver ablation/embolization or intensity-modulated radiation therapy may be beneficial.

Anaplastic thyroid cancer (ATC) is rare (encompassing <2% of all thyroid cancers) and has the highest mortality rate of all the thyroid cancers. Until recently, this disease was thought of as untreatable unless caught in a very early stage. However, recent advances, discussed herein, have started to change this perception.[6]

This review summarizes the rationale for using systemic therapy in advanced thyroid carcinoma, listing the approved drugs and their clinical indication. Relevant clinical trials and their preliminary data are also presented.