Predictive factors for first dose reduction and interruption of lenvatinib after beginning of the standard dose in Japanese patients with thyroid cancer

Abstract

Purpose: The associations between first dose reduction or interruption by side effects and lenvatinib plasma trough concentration (C₀) after administration of a starting dose of 24 mg in 70 Japanese patients with thyroid cancer were evaluated.

Methods: Plasma samples were collected each week for 1 month and at the first incidence of side effects leading to dose reduction or interruption after beginning administration of 24 mg lenvatinib.

Results: The area under the receiver operating characteristic curve was 0.789 at a lenvatinib C₀ threshold of 128.25 ng/mL for predicting the first dose reduction or interruption. The median time to the first dose reduction or interruption was 14.0 days in patients with a C₀ of ≥ 128.25 ng/mL and 21.0 days in those with a C₀ of < 128.25 ng/mL (P = 0.001). At one, two, three and four weeks respectively, the first dose reduction or interruption was associated with body weight (P = 0.034); sex (P = 0.021); sex, age, and lenvatinib C₀ of ≥ 128.25 ng/mL (P = 0.025, 0.024, and 0.048, respectively); and age and lenvatinib C₀ of ≥ 128.25 ng/mL (each P = 0.004).

Conclusions: On day 8 after administration of 24 mg lenvatinib, lenvatinib dose may be adjusted based on the target C₀ of 128.25 ng/mL to maintain a high dose intensity during this early phase; however, because persistence of a higher C₀ of 128.25 ng/mL causes early dose interruption or reduction, prospective dose reduction based on the next lower target C₀ for the maintenance phase may be necessary.

Keywords: Adverse events; Dose reduction; Lenvatinib; Plasma concentration.