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

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.

Analytical Validation of a Volumetric Absorptive Microsampling Method for Therapeutic Drug Monitoring of the Oral Targeted Anticancer Agents, Abiraterone, Alectinib, Cabozantinib, Imatinib, Olaparib, and Sunitinib, and Metabolites

“…3 Examples of such indications include cases of extreme toxicity, drug-drug interactions, uncertainty regarding drug adherence, or expected malabsorption. [4][5][6] Typically, TDM samples are retrieved during regular follow-up; however, this random timing of blood sampling is often not optimal for interpreting drug levels as many reference values are trough plasma concentrations. When the analytical method is not available locally, samples must be processed immediately and then shipped or stored under refrigerated conditions, thereby requiring efficient logistics.…”

“…3 Examples of such indications include cases of extreme toxicity, drug–drug interactions, uncertainty regarding drug adherence, or expected malabsorption. 4–6…”