Sunitinib for the treatment of metastatic gastrointestinal stromal tumors: the effect of TDM-guided dose optimization on clinical outcomes.

Autor:	Giraud EL; Department of Pharmacy, Radboud University Medical Center, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: https://twitter.com/ElineGirau45556., Westerdijk K; Department of Medical Oncology, Radboud University Medical Center, Radboud University Medical Center, Nijmegen, The Netherlands., van der Kleij MBA; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Guchelaar NAD; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Meertens M; Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Bleckman RF; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Rieborn A; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands., Mohammadi M; Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands., Roets E; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Huitema ADR; Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Pharmacology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Koolen SLW; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Department of Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands., Gelderblom H; Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands., Moes DJAR; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands., Reyners AKL; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Touw DJ; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Keizer-Heldens P; Department of Medical Oncology, Rijnstate Hospital, Arnhem, The Netherlands., Oosten AW; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van der Graaf WTA; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Steeghs N; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., van Erp NP; Department of Pharmacy, Radboud University Medical Center, Radboud University Medical Center, Nijmegen, The Netherlands., Desar IME; Department of Medical Oncology, Radboud University Medical Center, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Ingrid.desar@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	ESMO open [ESMO Open] 2024 Jun; Vol. 9 (6), pp. 103477. Date of Electronic Publication: 2024 Jun 03.
DOI:	10.1016/j.esmoop.2024.103477
Abstrakt:	Background: Sunitinib is an oral anticancer drug approved for the treatment of among others gastrointestinal stromal tumor (GIST). Previous analyses demonstrated an exposure-response relationship at the standard dose, and minimum target levels of drug exposure have been defined above which better treatment outcomes are observed. Therapeutic drug monitoring (TDM) could be used as a tool to optimize the individual dose, aiming at sunitinib trough concentrations ≥37.5 ng/ml for continuous dosing. Nonetheless, data on the added value of TDM-guided dosing on clinical endpoints are currently lacking. Therefore, we evaluate the effect of TDM in patients with advanced and metastatic GIST treated with sunitinib in terms of efficacy and toxicity. Patients and Methods: A TDM-guided cohort was compared to a non-TDM-guided cohort in terms of median progression-free survival (mPFS) and overall survival (mOS). Also, mPFS between patients with and without dose-limiting toxicities (DLTs) was compared. Patients in the prospective cohort were included in two studies on TDM-guided dosing (the DPOG-TDM study and TUNE study). The retrospective cohort consisted of patients from the Dutch GIST Registry who did not receive TDM-guided dosing. Results: In total, 51 and 106 patients were included in the TDM-guided cohort and non-TDM-guided cohort, respectively. No statistical difference in mPFS was observed between these two cohorts (39.4 versus 46.9 weeks, respectively; P = 0.52). Patients who experienced sunitinib-induced DLTs had longer mPFS compared to those who did not (51.9 versus 28.9 weeks, respectively; P = 0.002). Conclusions: Our results do not support the routine use of TDM-guided dose optimization of sunitinib in patients with advanced/metastatic GIST to improve survival. Competing Interests: Disclosure RHJM reports research funding paid to the institute from Astellas, Bayer, Boehringer-Ingelheim, Cristal Therapeutics, Novartis, Pamgene, Pfizer, Roche, Sanofi and Servier, all outside the submitted work. WTAvdG reports institutional research fees paid to the institute from Lilly and advisory compensation from Springworks, PTC Therapeutics and Agenus, all outside the submitted work. NS reports research grants paid to the institute from Abbvie, Actuate Therapeutics, Amgen, Array, Ascendis Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, BridgeBio, Bristol-Myers Squibb, Cantargia, CellCentric, Cogent Biosciences, Cresecendo Biologics, Cytovation, Deciphera, Dragonfly, Eli Lilly, Exelixis, Genentech, GlaxoSmithKline, IDRx, Immunocore, Incyte, InteRNA, Janssen, Kinnate Biopharma, Kling Biotherapeutics, Luszana, Merck, Merck Sharp & Dohme, Merus, Molecular Partners, Navire Pharma, Novartis, Numab Therapeutics, Pfizer, Relay Pharmaceuticals, Revolution Medicin, Roche, Sanofi, Seattle Genetics, Taiho and Takeda, all outside the submitted work. NS provided consultation or attended advisory boards for Boehringer Ingelheim, Cogent Biosciences, Ellipses Pharma, Incyte and Luszana. NPvE reports research funding paid to the institute from Astellas and Ipsen, all outside the submitted work. All other authors have declared no conflicts of interest. (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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