The treatment of differentiated thyroid cancer refractory to radioactive iodine (RAI) had been hampered by few effective therapies. Recently, tyrosine kinase inhibitors (TKIs) have shown activity in this disease. Clinical guidance on the use of these agents in RAI-refractory thyroid cancer is warranted.Molecular mutations found in RAI-refractory thyroid cancer are summarized. Recent phase II and III clinical trial data for TKIs axitinib, lenvatinib, motesanib, pazopanib, sorafenib, sunitinib, and vandetinib are reviewed including efficacy and side effect profiles. Molecular targets and potencies of these agents are compared. Inhibitors of BRAF, mammalian target of rapamycin, and MEK are considered.Routine testing for molecular alterations prior to therapy is not yet recommended. TKIs produce progression-free survival of approximately 1 year (range: 7.7-19.6 months) and partial response rates of up to 50% by Response Evaluation Criteria in Solid Tumors. Pazopanib and lenvatinib are the most active agents. The majority of patients experienced tumor shrinkage with TKIs. Common adverse toxicities affect dermatologic, gastrointestinal, and cardiovascular systems.Multiple TKIs have activity in RAI-refractory differentiated thyroid cancer. Selection of a targeted agent should depend on disease trajectory, side effect profile, and goals of therapy.
View details for DOI 10.1634/theoncologist.2014-0313
View details for Web of Science ID 000351915500007
View details for PubMedID 25616432
View details for PubMedCentralID PMC4319630