ArticleJournal of translational medicine2025
High BRAF variant allele frequency predicts poor outcomes in metastatic melanoma patients treated with BRAF/MEK inhibitors.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- Dynamic Time-Resolved Remodeling of the Immune Microenvironment After Resistance to BRAF/MEK Inhibitors in Melanoma: Mechanisms, Biomarkers, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Polyamine Metabolism and the DHPS/eIF5A Hypusination Axis: From Metabolic Reprogramming to a Therapeutic Achilles' Heel in Melanoma.Biomolecules · 2026Review
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38 authors.
Funding
Abstract
backgroundBRAF/MEK inhibitors have improved the outcome in metastatic melanoma (MM) patients harboring a BRAF mutation, but no biomarker predictive of response has been identified.
methodsWe conducted a retrospective analysis on 264 MM patients that had received first-line targeted therapy with BRAF/MEK inhibitors. Next-generation sequencing (NGS) was performed on tissue biopsies, and samples with > 30% tumor cellularity were included in the study. The impact of BRAF variant allele frequency (BRAF-VAF) on clinical treatment outcomes was analyzed.
resultsBRAF-VAF was dichotomized using two approaches. (1) The "surv_cutpoint" function identified two different cut-off for progression-free survival (PFS: 44.05%) and overall survival (OS:45.1%). Patients with BRAF-VAF > 44.05% showed a significantly lower PFS (median PFS: 10 months, 95% CI: 7-13 months), compared to patients with BRAF-VAF < 44.05% (median PFS: 13 months, 95% CI: 12-21 months). Moreover, patients with higher VAF (> 45.1%) experienced a lower OS (median OS: 26 months, 95% CI: 19-38 months), compared with patients with VAF < 45.1% (median OS: 29 months, 95% CI: 29-51 months). (2) The ROC analysis significantly predicted PFS but not OS. BRAF-VAF normalized with neoplastic cellularity (nVAF) showed a strong association with both PFS, and OS compared to BRAF-VAF alone. nVAF also emerged as an independent predictor for PFS in the multivariate analysis (HR: 3.88, 95% CI: 1.84-8.20), with a higher nVAF score associated with a 3.88-fold increased risk of progression.
conclusionsOur study demonstrated the role of the BRAF-VAF as predictor of response in MM patients treated with BRAF/MEK inhibitors. Moreover, VAF normalization predicts PFS better than BRAF-VAF alone.
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