Real-World Outcomes of Lenvatinib in Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Multicentre Retrospective Study

Background: Lenvatinib is an established first-line therapy for radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC); however, real-world data, particularly from Asian populations with long-term follow-up, remain limited. Methods: We conducted a multicentre retrospective cohort study across seven public hospitals in Hong Kong. Adult patients with RAI-refractory DTC who received lenvatinib between 1 January 2010 and 31 March 2025 were included. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and duration of treatment. Landmark analyses were performed at 6 and 12 months after lenvatinib initiation. Safety outcomes included treatment-related adverse events graded according to CTCAE version 5.0. Results: A total of 82 patients were included, with a median follow-up of 24.7 (IQR, 14.2–46.6) months. The median age at treatment initiation was 69 years, and the median starting dose of lenvatinib was 14 mg. Median PFS was 31.0 months (95% CI, 16.6–40.8) and median OS was 46.8 months (95% CI, 33.6–67.6), with multivariable analyses identifying brain metastasis as the most consistent adverse prognostic factor. The ORR was 52.4% and the DCR was 82.9%. Treatment-related adverse events were common, most frequently hypertension (73.2%) and proteinuria (57.3%); grade ≥ 3 events occurred predominantly as hypertension (45.1%). Conclusions: Lenvatinib achieved durable clinical outcomes in patients with RAI-refractory differentiated thyroid cancer despite the frequent use of reduced starting doses. Treatment-related toxicities were common but generally manageable, allowing prolonged treatment in many patients.