Low‐Dose Versus High‐Dose Lenvatinib in Radioiodine Refractory Differentiated Thyroid Cancer—A Real‐World Safety and Efficacy Analysis

ABSTRACT Objective Lenvatinib, a tyrosine kinase inhibitor, is approved for the treatment of radioiodine refractory differentiated thyroid cancer (RR‐DTC) at a dose of 24 mg/day. Given its significant toxicity profile, the present study aimed to compare the safety and efficacy of initial low‐dose lenvatinib to that of higher starting doses in patients with RR‐DTC. Methods This retrospective study included patients with RR‐DTC who were classified as: Group‐A: patients receiving 10mg/day, and Group‐B: patients receiving ≥ 14mg/day of lenvatinib as starting dose. Safety, radiological response (as per RECIST 1.1) and progression‐free survival (PFS) outcomes were analysed and compared. Results A total of 105 patients with RR‐DTC were included in this study (Group‐A: 60, Group‐B: 45). The study found that Group‐B experienced significantly higher rates of drug interruptions (68.9% vs 48.3%, p = 0.035) and dose reductions (60% vs 11.7%; p < 0.001) compared to Group‐A. Adverse events such as hand‐foot skin reaction (77.8% vs 58.3%), diarrhea (28.9% vs 11.7%), hepatotoxicity (33.3–40% vs 11.7–18.3%), and electrolyte imbalance (15.6% vs 3.3%) were also more frequent in Group‐B ( p ‐values < 0.05). However, both groups showed similar objective response rates (47.1% vs 46.3%; p = 0.936) and comparable PFS outcomes (restricted mean survival time at 24 months: 22.8 vs 21.4 months, p = 0.128). Conclusions The study suggests that starting with lower doses of lenvatinib, followed by dose escalation if tolerated, may offer a safer approach with significantly lower rates of drug interruptions and dose reductions, with comparable efficacy in RR‐DTC patients. Further validation by larger prospective trials is warranted.