BRAFV600 serum/plasma analysis: Predictive value of survival in melanoma treated with BRAF inhibitors.

Background: BRAF mutation is present in 50% of metastatic melanoma patients. Treatment with BRAF inhibitors improves survival of BRAF mutant melanoma patients, with a median progression free survival time of 6 months. Twenty percent of patients are refractory to BRAF inhibitors, and others have early resistance development. Pretreatment analysis of BRAFV600 mutation in cell free DNA from serum or plasma could help to select patients for BRAF inhibitor treatments. We have investigated the sensitivity of the assay and its predictive value. Methods: Analysis of BRAFV600 mutation was performed in cell free DNA (cf DNA) from serum and plasma of 22 metastatic melanoma patients before starting a BRAF inhibitor treatment. Results: Six patients were women, median age was 62 years old (58-81). Four patients (18%) had complete response to treatment. Eleven patients (50%) had partial response to treatment. Two patients (9%) had progression disease as their best response. Median progression free survival time (PFS) for patients with complete response, partial response, stable disease and progression disease were: not reached, 4.6 months, 3 months and one month, respectively (p<0.00001). Twelve patients (54.5%) had BRAF positive analysis pretreatment in serum/plasma. From BRAF serum/plasma positive patients 1 had CR (8%) and 7 PR (58%). From BRAF serum/plasma negative patients: 3 (30%) CR and 4 (40%) PR. Median PFS for patients treated with BRAF inhibitors was 3.5 months for BRAF serum/plasma positive patients and 13.57 months for BRAF serum/plasma negative patients (p=0.026) Conclusion: BRAFV600 serum/plasma analysis is a good predictor of survival for patients treated with BRAF inhibitors. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C41. Citation Format: Maria Gonzalez Cao, Salvador Martin Algarra, Eva Munoz, Clara Mayo de las Casas, Jose Luis Manzano, Javier Cortes, Miguel Angel Molina-Vila, Jose Pablo Berros, Leticia De Mattos-Arruda, Miguel Sanmamed, Alvaro Gonzalez, Carlos Alvarez, Niki Karachaliou, Rafael Rosell. BRAFV600 serum/plasma analysis: Predictive value of survival in melanoma treated with BRAF inhibitors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C41.