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19.05.2017 | Short Communication

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

verfasst von: Fanny Garlan, Benoit Blanchet, Nora Kramkimel, Alicja Puszkiel, Jean-Louis Golmard, Gaelle Noe, Nicolas Dupin, Pierre Laurent-Puig, Michel Vidal, Valerie Taly, Audrey Thomas-Schoemann

Erschienen in: Targeted Oncology | Ausgabe 3/2017

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Abstract

Background

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.

Objective

We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients.

Patients and Methods

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.

Results

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 concentrations. More interestingly, an inverse correlation between vemurafenib concentration and ctDNA concentrations was demonstrated (p = 0.026). The ctDNA concentration at baseline was associated with overall survival (hazard ratio = 2.61, 95% CI 1.04–6.56; p = 0.04).

Conclusions

This study demonstrates the relevance of vemurafenib plasma monitoring during the follow-up of metastatic melanoma patients. Plasma drug monitoring and ctDNA concentrations could be combined to monitor tumor evolution in melanoma patients treated with anti-BRAF therapies.

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Titel: Circulating Tumor DNA Measurement by Picoliter Droplet-Based Digital PCR and Vemurafenib Plasma Concentrations in Patients with Advanced BRAF-Mutated Melanoma
verfasst von: Fanny Garlan
Benoit Blanchet
Nora Kramkimel
Alicja Puszkiel
Jean-Louis Golmard
Gaelle Noe
Nicolas Dupin
Pierre Laurent-Puig
Michel Vidal
Valerie Taly
Audrey Thomas-Schoemann
Publikationsdatum: 19.05.2017
Verlag: Springer International Publishing
Erschienen in: Targeted Oncology / Ausgabe 3/2017
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-017-0491-8

Springer Medizin

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