Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKI) for optimized outcome in patients with metastatic renal cell carcinoma. The TKI-TDM Trial. Study protocol

Authors

  • Jakob N. Henriksen Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark https://orcid.org/0000-0003-0784-3206
  • Charlotte U. Andersen Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark; Department of Forensic Medicine, Aarhus University Hospital, Aarhus, Denmark https://orcid.org/0000-0003-0543-6519
  • Frede Donskov Department of Oncology, University Hospital of Southern Denmark, Esbjerg, Denmark; Department of Regional Health Science, University of Southern Denmark, Odense, Denmark https://orcid.org/0000-0002-8449-863X
  • Elke Hoffmann-Lücke Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark https://orcid.org/0000-0002-2437-0140
  • Eva Greibe Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark https://orcid.org/0000-0002-0417-1195
  • Niels Fristrup Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark https://orcid.org/0009-0006-4442-0535

DOI:

https://doi.org/10.2340/1651-226X.2025.43693

Keywords:

Metastatic renal cell carcinoma, tyrosine kinase inhibitors, therapeutic drug monitoring, personalized medicine, toxicity management

Abstract

Background: Metastatic renal cell carcinoma (mRCC) is notably resistant to chemotherapy and radiotherapy. However, tyrosine kinase inhibitors (TKIs) and checkpoint immunotherapy have significantly improved outcomes. Still, about 20% of patients experience disease progression as their best response to TKIs, and 16–63% endure severe toxicities, reducing quality of life. Optimizing dosing is therefore essential. Therapeutic drug monitoring (TDM) is a promising strategy for individualizing treatment. The TKI-TDM trial aims to identify a therapeutic plasma concentration range for six TKIs (axitinib, cabozantinib, pazopanib, sorafenib, sunitinib, tivozanib) in mRCC patients.

Material and methods: This prospective observational study will enroll mRCC patients with at least 6 months of stable disease or regression on TKI therapy. Blood samples will be collected during routine care. Plasma concentrations of TKIs and metabolites will be measured using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. These levels will be correlated with clinical outcomes including objective response rate, progression-free survival, overall survival, and toxicity. Genetic analysis of UGT1A1 polymorphisms will explore their influence on pazopanib metabolism and response.

Interpretation: Identifying plasma TKI levels associated with efficacy and reduced toxicity could minimize under- or overdosing, improving outcomes and quality of life. TDM may allow dose adjustments early in therapy, improving therapeutic management and reducing healthcare costs. Findings may also inform treatment of other cancers using TKIs or TKI-immunotherapy combinations. The trial (clinicaltrials.gov NCT04659343) is expected to conclude in 2028, with results in 2029.

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Published

2025-06-02

How to Cite

Henriksen, J. N., Andersen, C. U., Donskov, F., Hoffmann-Lücke, E., Greibe, E., & Fristrup, N. (2025). Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKI) for optimized outcome in patients with metastatic renal cell carcinoma. The TKI-TDM Trial. Study protocol. Acta Oncologica, 64, 729–733. https://doi.org/10.2340/1651-226X.2025.43693

Issue

Vol. 64 (2025): Acta Oncologica

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Short report

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Copyright (c) 2025 Jakob N. Henriksen, Charlotte U. Andersen, Frede Donskov, Elke Hoffmann-Lücke, Eva Greibe, Niels Fristrup

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This work is licensed under a Creative Commons Attribution 4.0 International License.