TY - JOUR
T1 - Precision Dosing of Targeted Therapies Is Ready for Prime Time
AU - Groenland, Stefanie L
AU - Verheijen, Remy B
AU - Joerger, Markus
AU - Mathijssen, Ron H J
AU - Sparreboom, Alex
AU - Beijnen, Jos H
AU - Beumer, Jan H
AU - Steeghs, Neeltje
AU - Huitema, Alwin D R
N1 - 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.
PY - 2021/12/15
Y1 - 2021/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85121128329&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-20-4555
DO - 10.1158/1078-0432.CCR-20-4555
M3 - Article
C2 - 34548319
SN - 1078-0432
VL - 27
SP - 6644
EP - 6652
JO - Clinical cancer research : an official journal of the American Association for Cancer Research
JF - Clinical cancer research : an official journal of the American Association for Cancer Research
IS - 24
ER -