Updates to Systemic Therapy for Differentiated Thyroid Cancer

Radioiodine-refractory differentiated thyroid cancer (DTC) encompasses a biologically diverse group of tumors that, once unresponsive to radioactive iodine, require systemic therapy decisions driven by timing, disease kinetics, molecular alterations, and patient preferences. Landmark trials have established multikinase inhibitors as the backbone of therapy for progressive radioiodine-refractory DTC, with lenvatinib emerging as the preferred agent. At the same time, next-generation sequencing has revealed a high prevalence of actionable genomic drivers in thyroid cancer, with RET and NTRK fusions as well as BRAF mutations offering opportunities for targeted therapy. This presentation discussed updated clinical strategies and NCCN Guidelines–aligned recommendations for the management of patients with advanced radioiodine-refractory DTC, based on recent data and evolving paradigms.