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Precision Dosing of Targeted Therapies Is Ready for Prime Time

Stefanie L Groenland, Remy B Verheijen, Markus Joerger, Ron H J Mathijssen, Alex Sparreboom, Jos H Beijnen, Jan H Beumer, Neeltje Steeghs & Alwin D R Huitema

abstract Fixed dosing of oral targeted therapies is inadequate in the era of precision medicine. Personalized dosing, based on pharmacokinetic (PK) exposure, known as therapeutic drug monitoring (TDM), is rational and supported by increasing evidence. The purpose of this perspective is to discuss whether randomized studies are needed to confirm the clinical value of precision dosing in oncology. PK-based dose adjustments are routinely made for many drugs and are recommended by health authorities, for example, for patients with renal impairment or for drug-drug interaction management strategies. Personalized dosing simply extrapolates this paradigm from selected patient populations to each individual patient with suboptimal exposure, irrespective of the underlying cause. If it has been demonstrated that exposure is related to a relevant clinical outcome, such as efficacy or toxicity, and that exposure can be optimized by PK-guided dosing, it could be logically assumed that PK-guided dosing would result in better treatment outcomes without the need for randomized confirmatory trials. We propose a path forward to demonstrate the clinical relevance of individualized dosing of molecularly-targeted anticancer drugs.
   
citation Groenland S L, Verheijen R B, Joerger M, Mathijssen R H J, Sparreboom A, Beijnen J H, Beumer J H, Steeghs N, Huitema A D R. Precision Dosing of Targeted Therapies Is Ready for Prime Time. Clin Cancer Res 2021; 27:6644-6652.
   
type journal paper/review (English)
date of publishing 21-09-2021
journal title Clin Cancer Res (27/24)
ISSN electronic 1557-3265
pages 6644-6652
PubMed 34548319
DOI 10.1158/1078-0432.CCR-20-4555