Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Although kinase inhibitors (KI) frequently portray large interpatient variability, a 'one size fits all' regimen is still often used. In the meantime, relationships between exposure-response and exposure-toxicity have been established for several KIs, so this regimen could lead to unnecessary toxicity and suboptimal efficacy. Dose adjustments based on measured systemic pharmacokinetic levels-i.e., therapeutic drug monitoring (TDM)-could therefore improve treatment efficacy and reduce the incidence of toxicities. Therefore, the aim of this comprehensive review is to give an overview of the available evidence for TDM for the 77 FDA/EMA kinase inhibitors currently approved (as of July 1st, 2023) used in hematology and oncology. We elaborate on exposure-response and exposure-toxicity relationships for these kinase inhibitors and provide practical recommendations for TDM and discuss corresponding pharmacokinetic targets when possible.

Automated summary

Although there is large interpatient variability with kinase inhibitors (KI), a 'one size fits all' regimen is still often used. However, dose adjustments based on therapeutic drug monitoring (TDM) using measured systemic pharmacokinetic levels could improve treatment efficacy and reduce toxicities. This comprehensive review provides an overview of the evidence for TDM in patients using 77 FDA/EMA-approved KIs in hematology and oncology, including exposure-response and exposure-toxicity relationships and practical recommendations for TDM.