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. 2021 Dec 14;13(24):6281.
doi: 10.3390/cancers13246281.

Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol

Anna M Mc Laughlin  1   2 , Eduard Schmulenson  3 , Olga Teplytska  3 , Sebastian Zimmermann  4 , Patrick Opitz  5 , Stefanie L Groenland  6 , Alwin D R Huitema  7   8   9 , Neeltje Steeghs  6 , Lothar Müller  10 , Stefan Fuxius  11 , Gerald Illerhaus  12 , Markus Joerger  13 , Frank Mayer  14 , Uwe Fuhr  15 , Stefan Holdenrieder  16 , Georg Hempel  5 , Oliver Scherf-Clavel  4 , Ulrich Jaehde  3 , Charlotte Kloft  1 , For The On-Target Study Consortium
Affiliations

Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol

Anna M Mc Laughlin et al. Cancers (Basel). .

Abstract

Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.

Keywords: oral anticancer drugs; renal cell carcinoma; therapeutic drug monitoring; volumetric absorptive microsampling.

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Conflict of interest statement

C.K. reports grants from an industry consortium (AbbVie Deutschland GmbH & Co. KG, AstraZeneca Ltd., Boehringer Ingelheim Pharma GmbH & Co. KG, Grünenthal GmbH, F. Hoffmann-La Roche Ltd., Merck KGaA and Sanofi) for the PharMetrX Graduate Research Training program and grants for DDMore within the Innovative Medicines Initiative-Joint Undertaking. O.S. reports endowed professorship grant (Horphag research Ltd.) and funding for the project ‘Individualized cancer therapy with kinase inhibitors using drug monitoring–optimization by minimally invasive at-home sampling’ (Hector Stiftung II gGmbH). NS reports research grants for the institute from GSK, Merck, Novartis, Pfizer and Roche for the Dutch DPOG-TDM study, further NS provided consultation or attended advisory boards for AIMM Therapeutics, Boehringer Ingelheim, Ellipses Pharma and NS received research grants for the institute from AB Science, Abbvie, Actuate Therapeutics, Amgen, Array, AstraZeneca/MedImmune, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Cantargia, CellCentric, Cytovation, Deciphera, Genentech/Roche, GlaxoSmithKline, Incyte, Lilly, Merck Sharp & Dohme, Merus, Molecular Partners, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Taiho, Takeda (outside the submitted work). GH serves as a consultant for AbbVie Canada. The remaining authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Overview of the ON-TARGET study framework. Abbreviations: PD: pharmacodynamics; PK: pharmacokinetics; TDM: therapeutic drug monitoring; VAMS: volumetric absorptive microsampling.
Figure 2
Figure 2
Stochastic simulations for an exemplary axitinib concentration-time profile. Green area: 50% prediction interval (25th–75th percentile), grey area: 90% prediction interval (5th–95th percentile). Letters (A–E) are explained in Section 2.4.5 in the main text.
See this image and copyright information in PMC

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