Validation of a Lenvatinib Assay: A Pilot Study

Lenvatinib has demonstrated efficacy in improving progression-free and overall survival in patients with radioiodine refractory thyroid cancer. However, treatment-related adverse events (TRAEs) frequently cause dose interruptions and suboptimal dosing, underscoring the importance of monitoring of lenvatinib levels. Currently, there is no validated lenvatinib assay for clinical use. We describe the development of a mass spectrometry assay for accurate quantification of lenvatinib, along with a pilot study reporting peak and trough levels.

A pilot prospective single-center study was conducted at Royal North Shore Hospital, to develop and validate an in-house high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for measuring plasma lenvatinib levels in patients with radioiodine refractory thyroid cancer. Patient data including dosage, TRAEs, and disease progression were recorded.

Lenvatinib doses ranged between 4 mg to 14 mg daily. Trough and peak levels were measured in nine and eight patients respectively. Duration of treatment ranged from 7 to 63 months (mean 29 months), with treatment duration at the time of testing ranging from 1 to 14 months. Trough levels ranged from 4.60 to 30.53 µg/L (median 21.74 µg/L). Peak levels for patients receiving 10 mg (n = 3) ranged from 78.50 to 237.72 µg/L (median 129.56 µg/L), while those receiving 14 mg (n = 4) ranged from 65.10 to 263.64 µg/L (median 185.23 µg/L).

Our study describes the successful development of a novel LC-MS/MS assay for quantifying plasma lenvatinib levels. Despite consistent dosing, we observed considerable variability in levels in this group. Further research is required to examine the utility of lenvatinib drug monitoring in the setting of thyroid cancer.