Objective: Lenvatinib, a multikinase inhibitor, is approved for treating radioiodine-refractory differentiated thyroid cancer (RR-DTC) with a standard starting dose of 24 mg/day. However, in unresectable hepatocellular carcinoma, the starting dose is adjusted based on body weight to manage dose interruptions and adverse events. This study investigates whether body weight impacts the efficacy and safety of lenvatinib in Japanese patients with RR-DTC.

Materials and Methods: We retrospectively analyzed the clinical records of 25 Japanese patients with RR-DTC treated from 2015 to 2023. We examined the relationship between body weight and the time to treatment-emergent adverse events (TEAEs) leading to dose reduction or discontinuation. Tumor response was assessed using CT scans according to RECIST ver. 1.1.

Results: Of the 25 patients, 11 (44.0%) experienced TEAEs leading to dose reduction or discontinuation within 28 days. The median body weight in this early dose reduction group was 50.2 kg, significantly lower than the 60.3 kg median in the control group (P = 0.03). Other clinical factors, such as tumor size and age, did not significantly affect the likelihood of early dose modification. Although tumor shrinkage was slightly less pronounced in the early dose reduction group, the difference was not statistically significant (p = 0.06). Survival rates were similar between the two groups (p = 0.76).

Conclusions: Lower body weight was associated with earlier dose reduction or discontinuation due to TEAEs, likely due to higher drug exposure in these patients. Adjusting the starting dose of lenvatinib according to body weight could improve the management of its toxicity in RR-DTC patients. Additionally, reevaluating the pharmacokinetics of lenvatinib in Japanese patients is recommended, considering their generally smaller physique compared to Western populations.