BACKGROUND. BRAF mutation is an oncogenic driver gene in NSCLC. Although the frequency is low, BRAF mutation represents a target for effective treatment in advanced stages of disease. Comprehensive data of patients with NSCLC harboring BRAF mutations are rare and inconsistent.

AIM. The study purpose was to investigate the phenotype of BRAF mutated NSCLC patients.

METHODS. All patients diagnosed with NSCLC (Jan 2020 - March 2022) harboring BRAF mutation were included. Clinical, radiological, functional and lab data were collected. For each sample, EGFR, KRAS, ALK, ROS1, and PD-L1 were also performed.

RESULTS. BRAF mutation was detected in 20/1031 (2%) NSCLC patients (18 V600E and 2 non-V600E subtypes). BRAF mutations were equally identified in both genders (F:50%, M:50%) with a mean age of 71±10 years. 15/20 (75%) were smokers (33±17 p.y.), 5/20 (25%) were exposed to professional hazards and 3/20 (15%) had a family history of lung cancer. 7/20 (35%) had previous/concomitant malignancies. 2/20 (10%) had obstructive flow limitation, 5/20 (25%) had reduced DLCO (65±18%). Extended opacities (9/20, 45%) and pleural effusion (3/20, 15%) were common findings at the onset with the majority (14/20, 70%) of patients in stage IV. 9/20 (45%) showed PD-L1 expression > 50%, 4/20 harbored co-occurrent molecular alterations (1 EGFR, 2 ROS1, 1 KRAS). At 9 months follow up, 12/20 (60%) survived. 9/12 received anti-BRAF targeted therapy, 3 underwent lung resection. 4/20 (20%) died before receiving any treatment.

CONCLUSIONS. BRAF is a rare mutation in NSCLC that can be targeted by specific therapies in advanced stages, The BRAF mutated patients? phenotype herein described is a step forward a better understanding of this NSCLC subset.