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Review
. 2023 Oct;62(10):1333-1364.
doi: 10.1007/s40262-023-01293-9. Epub 2023 Aug 16.

Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Maud B A van der Kleij #  1   2 , Niels A D Guchelaar #  3 , Ron H J Mathijssen  3 , Jurjen Versluis  4 , Alwin D R Huitema  5   6   7 , Stijn L W Koolen #  3   8 , Neeltje Steeghs #  9
Affiliations
Review

Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Maud B A van der Kleij et al. Clin Pharmacokinet. 2023 Oct.

Abstract

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.

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Conflict of interest statement

RHJM reported funding for investigator-initiated research from: Astellas, Bayer, Boehringer-Ingelheim, Cristal Therapeutics, Novartis, Pamgene, Pfizer, Roche, Sanofi & Servier. All outside the submitted work, and payment to the institute. NS provided consultation or attended advisory boards for Boehringer Ingelheim, Cogent Biosciences, Ellipses Pharma, Incyte, Luszana. N Steeghs received research grants from Abbvie, Actuate Therapeutics, Amgen, Array, Ascendis Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, BridgeBio, Bristol-Myers Squibb, Cantargia, CellCentric, Cogent Biosciences, Cresecendo Biologics, Cytovation, Deciphera, Dragonfly, Eli Lilly, Exelixis, Genentech, GlaxoSmithKline, IDRx, Immunocore, Incyte, InteRNA, Janssen, Kinnate Biopharma, Kling Biotherapeutics, Luszana, Merck, Merck Sharp & Dohme, Merus, Molecular Partners, Navire Pharma, Novartis, Numab Therapeutics, Pfizer, Relay Pharmaceuticals, Revolution Medicin, Roche, Sanofi, Seattle Genetics, Taiho, Takeda. All outside the submitted work, all payment to the Netherlands Cancer Institute. MvdK, NG, JV, AH and SK have declared no conflicts of interest.

Figures

Fig. 1
Fig. 1
An overview of the seven most important criteria for drugs to be a suitable candidate for therapeutic drug monitoring (TDM). Based on the requirements suggested by Groenland et al [7]. Created with Biorender.org
Fig. 2
Fig. 2
Overview of described KIs with target mechanism and indications used in solid tumors
Fig. 3
Fig. 3
Overview of described KIs with target mechanism and indications used in hematology
Fig. 4
Fig. 4
Summary figure with TDM targets for drugs with enough evidence to advise the use of TDM in clinical practice. Created with Biorender.org
See this image and copyright information in PMC

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