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

Abstract

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.

Keywords: Lenvatinib; Radioiodine; Thyroid cancer; Tyrosine kinase inhibitor.

Fig. 1. Flow chart of the study population enrollment

Fig. 2. Progression-free survival (A) and overall survival (B) for the complete patient series (n = 38)

Fig. 3. Comparisons of progression-free survival (PFS) and overall survival (OS) depending on the initial dose of lenvatinib (A, B), the dose interruption rate (C, D), the average overall daily dose per person (E, F), the average overall daily dose per kg body weight (G, H), age (I, J), sex (K, L), body weight (M, N), body mass index (O, P), malignant pleural effusion (Q, R), symptomatic metastases (S, T), tumor shrinkage rate (U, V), and serum thyroglobulin (Tg) regression rate (W, X). A hazard ratio (HR) with 95% confidence interval and a log-rank p-value for the group presented in the same color are provided in each panel.

Graphical Abstract