Optimizing Lenvatinib Therapy for Prognostic Improvement in Advanced Thyroid Cancer

Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is associated with poor prognosis and limited systemic options. This narrative review focuses on lenvatinib (LEN), a multitarget tyrosine kinase inhibitor that significantly prolongs progression-free survival. Evidence from the SELECT trial and real-world data indicates that its benefits can be enhanced through early initiation, maintenance of a high relative dose intensity, and proactive toxicity management. Planned drug holidays help sustain treatment while avoiding prolonged unplanned interruptions. In selected patients with locally advanced, initially unresectable disease, neoadjuvant LEN may enable conversion surgery, facilitating subsequent treatments. However, the current data are mainly from case series and early-phase studies. After dose reduction, re-escalation can restore disease control, and LEN rechallenge after a drug-free interval may restore sensitivity in later lines. Thus, LEN should be integrated into personalized multidisciplinary care to optimize outcomes across treatment courses. Nevertheless, key limitations remain, as much of the supporting evidence is derived from post hoc or retrospective analyses. Prospective studies are required to validate the optimization strategies, define stage-specific benefits, and determine their impact on overall survival.