Advances in the Treatment of Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Multikinase Inhibitors and Beyond – An Asian Perspective
22 Mar 2026
11:00
11:30
201BC
Won Gu KimSouth Korea
Speaker
Advances in the Treatment of Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Multikinase Inhibitors and Beyond – An Asian PerspectiveDifferentiated thyroid cancer (DTC) arising from follicular cells generally has a good prognosis; however, about 5-10% of patients experience recurrence or distant metastasis. High-dose radioactive iodine (RAI) therapy is the mainstay of treatment for metastatic DTC, but its efficacy depends on the iodine avidity of the tumor. Iodine uptake of metastatic lesions tends to decline over time, and ultimately, around 60-70% of metastatic cases become refractory to RAI therapy. Patients whose metastases remain RAI-avid have a median survival approaching 10 years, whereas those with RAI-refractory disease have a roughly 10% of 10 10-year survival. Because the clinical course of RAI-refractory DTC is variable, it is critical to determine which patients should receive systemic therapy with a tyrosine kinase inhibitor (TKI) and how to integrate local treatment before and during systemic therapy.
TKIs such as sorafenib and lenvatinib, which primarily inhibit tumor angiogenesis, have been approved. The DECISION trial reported that sorafenib achieved a median progression-free survival (PFS) of 10.8 months compared with 5.8 months in the control group. The SELECT trial showed that lenvatinib achieved a median PFS of 18.3 months versus 3.6 months in controls. Based on these results, sorafenib and lenvatnib are now widely used as the first-line treatments for patients with RAI-refractory DTC who have progressive or symptomatic metastatic disease. A recent multi-center real-world study in Korea suggested that lenvatinib provides better efficacy and longer PFS (median 35.3 months) than sorafenib (median 13.3 months, p<0.001). However, lenvatinib is also associated with higher rates of adverse events such as hypertension (95%) and proteinuria (80%). These TKIs show activity irrespective of the underlying genetic alterations that drive thyroid cancer.
Recently, selective NTRK and RET inhibitors have been developed for solid tumors harboring NTRK or RET gene fusions, and their efficacy has been confirmed in clinical trials. In addition, genetic testing to identify actionable mutations is increasingly being incorporated into practice, and personalized treatment approaches are reflected in current clinical guidelines. A recent Korean multicenter study found that approximately 31% of patients with RAI-refractory thyroid cancer who had wild-type BRAF carried targetable gene fusions. The choice and sequencing of TKI, the optimal timing of their use, strategies to prevent and manage adverse events, and individualized treatment plans based on patient characteristics will be crucial for improving clinical outcomes in patients with RAI-refractory thyroid cancer.