Lenvatinib in radioiodine-refractory differentiated thyroid cancer: a real-world institutional analysis

Lenvatinib is a standard systemic therapy for radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). Although pivotal trials such as SELECT demonstrated significant efficacy, real-world evidence remains limited, particularly regarding treatment timing and the role of planned drug holidays. We retrospectively analyzed 44 consecutive patients with RAI-R DTC treated with lenvatinib between 2015 and 2024. All patients initiated therapy at 24 mg/day, with dose reductions and treatment interruptions-including planned drug holidays-implemented according to toxicity. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and best tumor shrinkage. A subgroup analysis was conducted in patients with lung metastases. The median PFS was 36.0 months, and the median OS was 76.7 months. ORR was 52.3% and DCR was 95.5%. In the lung metastases-only subgroup (n = 25), outcomes were particularly favorable: PFS 58.1 months, unreached OS, ORR 64.0%, and DCR 100%. Univariate Cox analysis identified performance status, histological subtype, TV-DT, and tumor burden as significant prognostic factors. The most common adverse events were hypertension, proteinuria, fatigue, and palmar-plantar erythrodysesthesia; these were generally manageable with dose adjustments and individualized planned holidays. Clinically meaningful renal dysfunction was rare despite frequent proteinuria. Lenvatinib demonstrated durable efficacy and acceptable tolerability in real-world practice, especially in patients with lung metastases. Early treatment initiation and individualized toxicity management-including planned drug holidays-enabled sustained dose intensity and prolonged disease control. These findings support the clinical utility of personalized adverse event management strategies in routine care for RAI-R DTC.