Assessment of BRAF mutations and their predictive value in patients with advanced melanoma treated with immune checkpoint inhibitors

• Grant number: 25/07083-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Lidia Maria Rebolho Batista Arantes
• Grantee: Hendrigo Nunes
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated research grant: 19/07111-9 - Immune-checkpoint inhibitors: immunophenotyping and clinical outcome to predict response at Barretos Cancer Hospital, AP.JP

Abstract

Justification: The heterogeneous clinical outcomes observed in patients with advanced melanoma treated with immune checkpoint inhibitors highlight the need to identify predictive biomarkers of response. In this context, the BRAF gene emerges as a potential predictive biomarker due to its activating mutations found in approximately 50% of melanomas, which induce a tumor microenvironment distinct from that observed in BRAF wild-type melanomas. Although BRAF status is already used as a criterion for targeted therapies, its predictive value in immunotherapy remains underexplored. Objectives: This proposal aims to evaluate the association between the mutational status of the BRAF gene and the clinical outcomes of patients with advanced melanoma treated with immunotherapy. Materials and Methods: This is an observational, cross-sectional study based on the retrospective collection of clinical data and tumor samples from approximately 200 patients with advanced melanoma (unresectable stage III and stage IV) treated with anti-PD-1 and/or anti-CTLA-4 agents at Hospital de Amor between 2011 and 2024. Tumor samples will undergo DNA extraction and BRAF V600 mutation analysis via pyrosequencing, with findings compared to those obtained by Cobas® or NGS. Treatment response will be assessed according to iRECIST criteria, and mutational data will be correlated with immunotherapy response and survival outcomes, using a significance level of p < 0.05.