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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.

J M van Berge Henegouwen ,
H van der Wijngaart ,
L J Zeverijn ,
L R Hoes ,
M Meertens ,
A D R Huitema ,
L A Devriese ,
M Labots ,
H M W Verheul ,
E E Voest ,
H Gelderblom

Abstract

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.

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.

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 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.

TRIAL REGISTRATION

Clinical trial identification: NCT02925234.

More about this publication

Cancer chemotherapy and pharmacology

Volume 90
Issue nr. 1
Pages 97-104
Publication date 01-07-2022

Full text links

Publisher website (DOI) 10.1007/s00280-022-04437-z
Europe PubMed Central 35598186
Pubmed 35598186

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