Background: Lenvatinib improves progression-free and overall survival for radioiodine refractory thyroid cancer. Significant treatment-related adverse effects (TRAEs) can necessitate dose interruptions and suboptimal dosing. Plasma lenvatinib levels are not routinely employed as there is no validated assay for clinical use.
Purpose: To develop a mass-spectometry assay that accurately measures lenvatinib levels and identify normal range peak and trough levels which may correlate with TRAEs.
Methods: A pilot prospective single centre study was performed at Royal North Shore Hospital Sydney. An in-house LC MS/MS assay on a reverse phase column using a 4 minute gradient run was developed to measure lenvatinib levels. Extraction by protein precipitation of plasma samples using methanol with removal of the supernatant before introduction to the column yielded a drug level (ug/L). Available patient dosage, TRAEs and disease progress were recorded.
Results: We collected trough lenvatinib levels in nine and peak (2 hours post administration) levels in eight patients with radioiodine refractory thyroid cancer. Doses ranged between 4-14mg daily. Duration on lenvatinib ranged between 7-63 months (mean 29 months). Duration of treatment on dose of medication at time of testing ranged between 1-14 months. Trough levels ranged between 4.60-30.53ug/L (mean 18.97ug/L). Peak levels for patients on 10mg (n=3) ranged between 78.50- 237.72 ug/L (mean 148.59 ug/L) and on 14mg (n=4) ranged between 65.10-263.64 ug/L (mean 174.80 ug/L). Of note, the case with the lowest trough level was the only participant without hypertension.
Discussion: Access to accurate drug levels may improve monitoring of patients on lenvatinib. Potential to adjust dosing prior to TRAEs occurring and so facilitate more sustained treatment courses still requires exploration.
Conclusion: A novel lenvatinib assay was developed to evaluate peak and trough levels. A large range within the same dose was demonstrated.