Feasibility of therapeutic drug monitoring of sorafenib in patients with liver or thyroid cancer

INTRODUCTION: Sorafenib is a tyrosine-kinase inhibitor approved for the treatment of renal cell carcinoma, hepatocellular carcinoma, thyroid carcinoma, and desmoid fibromatosis. As high inter-individual variability exists in exposure, there is a scientific rationale to pursue therapeutic drug monitoring (TDM). We investigated the feasibility of TDM in patients on sorafenib and tried to identify sub-groups in whom pharmacokinetically (PK) guided-dosing might be of added value.

METHODS: We included patients who started on sorafenib (between October 2017 and June 2020) at the recommended dose of 400 mg BID or with a step-up dosing schedule. Plasma trough levels (C trough) were measured at pre-specified time-points. Increasing the dose was advised if C trough was below the target of 3750 ng/mL and toxicity was manageable.

RESULTS: A total of 150 samples from 36 patients were collected. Thirty patients (83 %) had a C trough below the prespecified target concentration at a certain time point during treatment. Toxicity from sorafenib hampered dosing according to target C trough in almost half of the patients. In 11 patients, dosing was adjusted based on C trough. In three patients, this resulted in an adequate C trough without additional toxicity four weeks after the dose increase. In the remaining eight patients, dose adjustment based on C trough did not result in a C trough above the target or caused excessive toxicity.

CONCLUSIONS: TDM for sorafenib is not of added value in daily clinical practice. In most cases, toxicity restricts the possibility of dose escalations.