Current Standards in Treatment of Radioiodine Refractory Thyroid Cancer.

OPINION STATEMENT: Radioiodine refractory differentiated thyroid cancer (RAI-R DTC) is a challenging malignancy with limited prognosis and treatment options. Recently, clinical trials with targeted therapies have advanced the outlook of these patients, and inhibition of the vascular endothelial growth factor (VEGF) axis has led to the approval of small-molecule tyrosine kinase inhibitors (TKIs) for first-line treatment of radioiodine refractory disease. In addition to approved therapies (sorafenib and lenvatinib), other multi-targeted tyrosine kinase inhibitors that are commercially available have been recognized as viable treatment options for RAI-R DTC. Our preference is to initially use lenvatinib, given the dramatic progression-free survival (PFS) improvement versus placebo, with the caveat that 24 mg daily is not often tolerated and lower doses often used. In patients with BRAF V600E mutation, BRAF inhibitors are now considered for treatment, especially if patients are at high risk from antiangiogenic therapy. Research is continuing to evolve in identifying mechanisms related to radioiodine refractoriness, and trials are evaluating therapeutic molecules to overcome this resistance. Clinical care of patients with RAI-R DTC requires careful consideration of both patient and disease characteristics. Many patients with asymptomatic and indolent disease can be followed for years without treatment while others with high volume or rapidly progressive disease merit early intervention.