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

Abstract

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.