BRAFV600 variant allele frequency predicts outcome in metastatic melanoma patients treated with BRAF and MEK inhibitors.

Autor: Mandalà M; University of Perugia, Perugia, Italy.; Unit of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy., Palmieri G; Immuno-Oncology & Targeted Cancer Biotherapies, University of Sassari, Sassari, Italy.; Unit of Cancer Genetics, IRGB-CNR, Sassari, Italy., Ludovini V; Unit of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy., Baglivo S; Unit of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy., Marasciulo F; Unit of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy., Castiglione F; Histopathology and Molecular Diagnostics, Careggi University Hospital, Florence, Italy., Gili A; Unit of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy., Osella Abate S; Pathology Unit, Department of Medical Sciences, University of Torino, Torino, Italy., Rubatto M; Dermatology Unit, Department of Medical Sciences, University of Torino, Torino, Italy., Senetta R; Pathology Division, 'Città della Salute e della Scienza di Torino' University Hospital, Torino, Italy., Avallone G; Dermatology Unit, Department of Medical Sciences, University of Torino, Torino, Italy., Ribero S; Dermatology Unit, Department of Medical Sciences, University of Torino, Torino, Italy., Romano L; Unit of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy., Pimpinelli N; Unit of Dermatology, Department of Health Sciences, University of Florence Medical School, Florence, Italy., de Giorgi V; Unit of Dermatology, Department of Health Sciences, University of Florence Medical School, Florence, Italy., Roila F; University of Perugia, Perugia, Italy.; Unit of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy., Pisano M; Unit of Cancer Genetics, IRGB-CNR, Sassari, Italy., Casula M; Unit of Cancer Genetics, IRGB-CNR, Sassari, Italy., Manca A; Unit of Cancer Genetics, IRGB-CNR, Sassari, Italy., Sini MC; Unit of Cancer Genetics, IRGB-CNR, Sassari, Italy., Massi D; Section of Pathology, Department of Health Sciences, University of Florence, Florence, Italy., Quaglino P; Dermatology Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
Jazyk: angličtina
Zdroj: Journal of the European Academy of Dermatology and Venereology : JEADV [J Eur Acad Dermatol Venereol] 2023 Oct; Vol. 37 (10), pp. 1991-1998. Date of Electronic Publication: 2023 Jun 27.
DOI: 10.1111/jdv.19281
Abstrakt: Background: The prognostic impact of variant allele frequency (VAF) on clinical outcome in BRAFV600 mutated metastatic melanoma patients (MMPs) receiving BRAF (BRAFi) and MEK inhibitors (MEKi) is unclear.
Materials and Methods: A cohort of MMPs receiving first line BRAFi and MEKi was identified by inspecting dedicated databases of three Italian Melanoma Intergroup centres. VAF was determined by next generation sequencing in pre-treatment baseline tissue samples. Correlation between VAF and BRAF copy number variation was analysed in an ancillary study by using a training and a validation cohort of melanoma tissue samples and cell lines.
Results: Overall, 107 MMPs were included in the study. The VAF cut-off determined by ROC curve was 41.3%. At multivariate analysis, progression-free survival (PFS) was significantly shorter in patients with M1c/M1d [HR 2.25 (95% CI 1.41-3.6, p < 0.01)], in those with VAF >41.3% [HR 1.62 (95% CI 1.04-2.54, p < 0.05)] and in those with ECOG PS ≥1 [HR 1.82 (95% CI 1.15-2.88, p < 0.05)]. Overall survival (OS) was significantly shorter in patients with M1c/M1d [HR 2.01 (95% CI 1.25-3.25, p < 0.01)]. Furthermore, OS was shorter in patients with VAF >41.3% [HR 1.46 (95% CI 0.93-2.29, p = 0.06)] and in patients with ECOG PS ≥1 [HR 1.52 (95% CI 0.94-2.87, p = 0.14)]. BRAF gene amplification was found in 11% and 7% of samples in the training and validation cohort, respectively.
Conclusions: High VAF is an independent poor prognostic factor in MMP receiving BRAFi and MEKi. High VAF and BRAF amplification coexist in 7%-11% of patients.
(© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
Databáze: MEDLINE
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