Multicenter Observational Study on Metastatic Non-Small Cell Lung Cancer Harboring BRAF Mutations: Focus on Clinical Characteristics and Treatment Outcome of V600E and Non-V600E Subgroups

SIMPLE SUMMARY: Around 2–4% of lung adenocarcinoma harbors BRAF mutations. Dabrafenib and Trametinib represent the first treatment-choice for BRAF V600E(mut) NSCLC, regardless of the line of therapy, while non-V600E(mut) receive standard immunotherapy or chemo-immunotherapy. Our real-life multicenter study on 44 BRAF mutant NSCLC responds to the urgent need to characterize this subset of patients in-depth, potentially offering new valuable biological and clinical insights. We specifically focused on similarities/discrepancies between V600E and non-V600E populations, providing consistent data about clinicopathologic characteristics, treatment response, and survival outcome. ABSTRACT: Introduction: BRAF mutation involved 2–4% of lung adenocarcinoma. Differences in clinicopathologic features and patient outcome exist between V600E and non-V600E BRAF mutated NSCLC. Thus, we sought to assess the frequency and clinical relevance of BRAF mutations in a real-life population of advanced-NSCLC, investigating the potential prognostic significance of distinct genetic alterations. Materials and Methods: The present multicenter Italian retrospective study involved advanced BRAF mutant NSCLC. Complete clinicopathologic data were evaluated for BRAF V600E and non-V600E patients. Results: A total of 44 BRAF(mut) NSCLC patients were included (V600E, n = 23; non-V600E, n = 21). No significant differences in survival outcome and treatment response were documented, according to V600E vs. non-V600E mutations, although a trend towards prolonged PFS was observed in the V600E subgroup (median PFS = 11.3 vs. 6.0 months in non-V600E). In the overall population, ECOG PS and age significantly impacted on OS, while bone lesions were associated with shorter PFS. Compared to immunotherapy, first-line chemotherapy was associated with longer OS in the overall population, and especially in the BRAF V600E subtype. Conclusions: Here, we report on real-life data from a retrospective cohort of advanced-NSCLC harboring BRAF alterations. Our study offers relevant clues on survival outcome, therapeutic response, and clinicopathologic correlations of BRAF-mutant NSCLC.