Clinical Features And Outcome Of Chinese Patients With Lung Cancer Harboring BRAF Mutations

Background:Inhibitors targeting active protein kinases, such as EGFR or ALK, have demonstrated significant efficacy in the treatment of lung cancer. Activating mutations in the MAPK pathway, leading to oncogenic cell proliferation and escape from apoptosis; therefore this pathway is a focus of crucial interest for the development of cancer drugs. In melanoma, the most commonly mutated gene is BRAF, with mutations usually occurring in about50%of all tumours. The BRAF Va1600Glu (V600E) mutation constitutes more than90%of mutations in melanoma. V600E BRAF mutation shows a great dependency on MEK activity, and offers a rational therapeutic strategy for this genetically defined tumour subtype. The use of vemurafenib and dabrafenib, agents that block MAPK signaling in patients with melanoma and the BRAF V600E mutation, has been associated with prolonged survival and progression-free survival. The frequency of V600E BRAF mutation in lung cancer is1%to3%. Treatment of V600E BRAF-mutant lung adenocarcinomas with dabrafenib is under evaluation in a phase2trial, and could represent another milestone in individualized therapy for lung cancer patients.Patients and Methods:We reviewed data from5125consecutive patients with lung cancer whose tumors underwent BRAF, EGFR, KRAS and PIK3CA mutation testing, and identify25patients with BRAF V600E mutation. Patient characteristics including age,sex, smoking history, stage, treatment history, and overall survival were collected.Results:Together, there were36.2%patients with EGFR mutations (1854/5125);8.4%, KRAS mutations (429/5125);0.5%, BRAF mutations (26/5125) and3.3%, PIK3CA mutations (167/5125).2072of them were female (40.4%) and3053, male (59.6%). Patient ages ranged from five to91years old with the median age of59years old. Cancer forms were identified in1177of patients tested:977samples were adenocarcinomas while only200were squamous cell carcinomas. Patients with BRAF V600E mutations were almost never smokers (P<0.01). The median overall survival of advanced-stage patients with V600E mutations was20mo. There were no significant differences in OS for advanced-stage patients with V600E mutations compared with patients with coexistant EGFR/PIK3CA mutations.Conclusion:BRAF V600E mutations occur in0.5%of patients with lung cancer. It occurs more commonly in females and never smokers. Patients with V600E mutation are not sensitive to EGFR TKIs.