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, 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

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.

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.

Keywords: Case series; Cobimetinib; Feeding tube; Plasma concentrations; Thyroid carcinoma; Vemurafenib.

Conflict of interest statement

All authors declare that they have no conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Trough plasma concentrations of vemurafenib and cobimetinib for patient 1 during the course of the treatment. Dosage and treatment interruptions, co-medication and adverse events are presented below the chart. Cmin trough concentration, OD once daily, BID twice daily, TID thrice daily, PPI proton-pump inhibitor, SUSAR Suspected Unexpected Serious Adverse Reaction
Fig. 2
Fig. 2
Trough plasma concentrations of vemurafenib and cobimetinib for patient 2 during the course of the treatment. Dosage and treatment interruptions and adverse events are presented below the chart. Cmin trough concentration, OD once daily, BID twice daily

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