Efficacy and toxicity of vemurafenib and cobimetinib in relation to plasma concentrations, after administration via feeding tube in patients with BRAF-mutated thyroid cancer: a case series and review of literature
van Berge Henegouwen, J M; van der Wijngaart, H; Zeverijn, L J; Hoes, L R; Meertens, M; Huitema, A D R; Devriese, L A; Labots, M; Verheul, H M W; Voest, E E; Gelderblom, H
(2022) Cancer Chemotherapy and Pharmacology, volume 90, issue 1, pp. 97 - 104
(Article)
Abstract
INTRODUCTION: The combination of vemurafenib, a proto-oncogene B-Raf inhibitor (BRAFi) and cobimetinib, an inhibitor of mitogen-activated protein kinase kinase (MEKi) has shown to improve survival in patients with BRAF V600-mutated melanoma. BRAF mutations are also frequently detected driver mutations in other tumor types, including thyroid carcinoma. Since thyroid carcinoma is
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not a labeled indication for BRAF/MEKi, a cohort for patients with BRAF V600-mutated thyroid carcinoma was opened within the Drug Rediscovery Protocol (DRUP), a national ongoing pan-cancer multi-drug trial, in which patients receive off-label treatment with approved drugs based on their molecular tumor profile. RESULTS: Here, we present two patients with BRAF-mutated thyroid carcinoma, who were successfully treated with vemurafenib/cobimetinib administered via a feeding tube. Plasma concentrations of vemurafenib and cobimetinib were determined. A partial response was observed in both patients, but they experienced significant toxicity. CONCLUSION: Our cases show that vemurafenib/cobimetinib treatment is effective in BRAF V600-mutated thyroid carcinoma, also when administered via a feeding tube. Although serious side effects occurred in both patients, we hypothesize that this was not attributable to the administration route. Therefore, administration of vemurafenib/cobimetinib by feeding tube is feasible and effective. TRIAL REGISTRATION: Clinical trial identification: NCT02925234.
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Keywords: Case series, Cobimetinib, Feeding tube, Plasma concentrations, Thyroid carcinoma, Vemurafenib, Pharmacology (medical), Oncology, Cancer Research, Toxicology, Pharmacology, Journal Article
ISSN: 0344-5704
Publisher: Springer-Verlag
Note: Funding Information: The patients described in the current work were treated as part of the DRUP trial. the DRUP trial is supported by the Barcode for Life Foundation (BFL); the Dutch Cancer Society [grant number 10014]; the Hartwig Medical Foundation (HMF) and all participating pharmaceutical companies: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Clovis Oncology; Eisai; Janssen; Lilly; MSD; Novartis; Pfizer; Roche, and Hartwig Medical Foundation, Dutch Cancer Society (KWF) and Barcode for Life Foundation (BFL). Publisher Copyright: © 2022, The Author(s).
(Peer reviewed)