2024 World Conference on Lung Cancer (WCLC) - Posters-P3.12C.01 BRAF Mutation Diversity and Impact on Clinical Outcomes in Non-Small Cell Lung Cancer

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The study focuses on the diversity and clinical outcomes associated with different classes of BRAF mutations in non-small cell lung cancer (NSCLC). BRAF mutations are present in about 5% of NSCLC cases and are categorized into three classes: Class I (active monomers), Class II (active dimers), and Class III (kinase-dead). The research aims to determine the therapeutic implications of these BRAF variants using clinical data and chemical drug screenings.<br /><br />Findings indicate that in Class I BRAF mutants, treatment with a combination of anti-BRAF and anti-MEK therapies leads to significantly improved overall survival (median OS of 40 months compared to 10 months) and a higher percentage of co-occurring MAPK pathway genetic alterations compared to Class II and III. Furthermore, distinct tumor mutation burdens were observed across the BRAF classes, which may imply different efficacies of immunotherapy for each class.<br /><br />For Class II and III BRAF mutants, there are currently no FDA-approved targeted therapies. However, in vitro drug testing showed that cell lines of these classes exhibit cell death when treated with specific EGFR and BRAF inhibitors. These findings suggest a potential clinical value for ERK, MEK, and pan-RAF inhibitors in Class II and III mutant cases, but further research is needed.<br /><br />The study utilized a retrospective multi-institutional analysis, examining clinical characteristics and co-alterations of each BRAF class using data from the cBioPortal cancer genomics database. The research emphasizes the need to explore targeted therapies beyond those currently approved for BRAF V600E-mutant NSCLC, particularly for less common BRAF mutations.<br /><br />In conclusion, while combination therapies exist for Class I BRAF mutations, greater efforts and further analyses are necessary to address the therapeutic challenges associated with Class II and III BRAF mutations in NSCLC.

Asset Subtitle

Kevin Lu

Meta Tag

Speaker Kevin Lu

Topic Metastatic NSCLC – Targeted Therapy

Keywords

BRAF mutations

non-small cell lung cancer

NSCLC

clinical outcomes

therapeutic implications

drug screening

Class I BRAF

Class II BRAF

Class III BRAF

targeted therapies