Circulating Tumor DNA Measurement by Picoliter Droplet-Based Digital PCR and Vemurafenib Plasma Concentrations in Patients with Advanced BRAF-Mutated Melanoma

Targeted Oncology
Fanny GarlanA Thomas-Schoemann

Abstract

Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis. We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients. Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study. The vemurafenib plasma concentration was measured by liquid chromatography. ctDNA was extracted from plasma samples and the ctDNA concentration was evaluated using picoliter droplet-based digital PCR with Taqman®detection probes targeting the BRAF p.V600E/K mutation and wild-type BRAF sequences. At baseline, plasma ctDNA was detectable in 72% (n = 8/11) of patients and the ctDNA concentration decreased in 88% of these patients (n = 7/8) from day (D) 0 to D15 after vemurafenib initiation. During follow-up, an increased ctDNA concentration was detected in nine patients: in five patients, the first increase in ctDNA concentrations followed a decrease in vemurafenib concentratio...Continue Reading

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Nov 9, 2017·Expert Review of Molecular Diagnostics·Mathilde PostelShu-Fang Wang-Renault
Sep 27, 2018·Journal of Otolaryngology - Head & Neck Surgery = Le Journal D'oto-rhino-laryngologie Et De Chirurgie Cervico-faciale·Vincent L BironDaniel A O'Connell
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