Real-world clinical experience of reduced-dose initiation of lenvatinib in Japanese patients with radioiodine-refractory differentiated thyroid cancer.

Lenvatinib is approved for the first-line treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC) at a starting dose of 24 mg/day, but its high toxicity often necessitates dose reductions and interruptions. To clarify the efficacy and safety of the reduced dose-initiation of lenvatinib, especially for smaller-build and/or frail Asians, we retrospectively examined outcomes of 43 Japanese individuals with RR-DTC who were treated with lenvatinib, focusing on the initial dose. Twenty-three patients initiated lenvatinib at a full-dose (24 mg/day) and 20 patients initiated at a reduced-dose (≤14 mg/day). In the full dose-initiation group, 14 of 23 (60.8%) patients required discontinuation of lenvatinib within ~30 days due to adverse effects, which was significantly higher rate compared to that (25.0%) of the reduced dose-initiation group (p = 0.018), and 5 patients of the full dose-initiation group did not resume treatment. Compared to the full dose-initiation group, the reduced dose-initiation group were older (nonsignificant) and had significantly lower body weights, lower overall daily dose exposure, and a lower frequency of adverse events (≥grade 2) but a comparable dose interruption rate and daily dose exposure per kg during overall observation period. In multivariate analyses for progression-free survival and overall survival, malignant pleural effusion and symptomatic metastases but not the starting dose of lenvatinib were significantly associated with worse outcomes. Initiating lenvatinib at a reduced dose based on patients' physical status may be an option, with not only lower adverse events but also efficacy comparable to that of the full dose.