Target Attainment and Clinical and Biochemical Parameters Associated with the Pharmacokinetics of 12 Tyrosine Kinase...

Tyrosine kinase inhibitors (TKIs) are targeted cancer therapies. However, TKIs are still limited due to their high inter-individual variability. This study evaluated target attainment using therapeutic drug monitoring (TDM) data from 12 TKIs, and investigated biochemical and patient-related characteristics influencing TKI pharmacokinetics (PK) METHODS: This single-centre retrospective study included cancer patients treated with TKIs between January 2020 and August 2024. Demographic, clinical, and biochemical data were extracted from electronic health records. Univariate and multivariate linear mixed models were used to identify factors associated with TKI PK.

A total of 1237 TKI concentrations from 309 patients were included. Target attainment percentages were: 74.6% for alectinib; 70% for bosutinib; 49.9-61.9% for imatinib depending on the indication; 88.9% for nilotinib; 50% for pazopanib; 50% for ponatinib; 89.5% for regorafenib; 26.6% for sunitinib; ibrutinib, lenvatinib and trametinib had too few data for formal assessment; 40-87.5% for dasatinib, depending on indication and parameter (C_max or C_min). A mixed linear model analysis identified key parameters correlated with TKI concentrations. Glomerular filtration rate was correlated with alectinib, imatinib, and sunitinib. Alkaline phosphatase (ALP), bilirubin, and Gamma-GT correlated with alectinib and ALP with imatinib. Albumin and thrombocytes correlated with imatinib, thrombocytes with pazopanib, absolute neutrophiles count (ANC) with ponatinib, and haematocrit with regorafenib.

Target attainment was suboptimal for most TKIs, supporting the need for TDM-guided optimisation and individualised dosing. Associations between TKI exposure and renal, hepatic, and haematological parameters further support personalised treatment strategies.