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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6644-6652
Number of pages9
JournalClinical Cancer Research
Volume27
Issue number24
DOIs
Publication statusPublished - 15 Dec 2021

Bibliographical note

Funding Information:
R.B. Verheijen reports other support from Johnson & Johnson, AstraZeneca, Galapagos, and Chinook Tx outside the submitted work. R.H.J. Mathijssen reports grants from Astellas, Bayer, Boehringer Ingelheim, Cristal Therapeutics, Novartis, Pamgene, Pfizer, Roche, Sanofi, and Servier outside the submitted work. N. Steeghs reports grants from AB Science, AbbVie, Actuate Therapeutics, AIMM Therapeutics, Amgen, Array, AstraZeneca/MedImmune, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Cantargia, CellCentric, Cytovation, Deciphera, Ellipses Pharma, Genentech/Roche, GlaxoSmithKline, Incyte, Lilly, Merck Sharp & Dohme, Merus, Molecular Partners, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Taiho, and Takeda outside the submitted work. A.D.R. Huitema reports grants from Roche, Novartis, and Pfizer during the conduct of the study. No disclosures were reported by the other authors.

Funding Information:
J.H. Beumer was supported by NCI grants UM1CA186690 and P30CA47904.

Publisher Copyright:
© 2021 American Association for Cancer Research.

Fingerprint

Dive into the research topics of 'Precision Dosing of Targeted Therapies Is Ready for Prime Time'. Together they form a unique fingerprint.

Cite this