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

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.