Frequency and clinical features of BRAF mutations among patients with stage III/IV lung adenocarcinoma without EGFR/ALK aberrations.

Objective: BRAF mutations are found in 1-5% of non-small cell lung cancers, particularly adenocarcinomas. However, information regarding this mutation is limited in patients without EGFR/ALK aberrations, who have limited treatment options.

Methods: The medical records of 224 stage III/IV adenocarcinoma patients without EGFR/ALK aberrations and with available pathologic tissue, were retrospectively reviewed. BRAF mutations were evaluated using a PNAClampTM BRAF mutation detection kit (Panagene, Daejeon, Korea). The outcomes in the study population were compared with stage III/IV adenocarcinoma patients harboring an EGFR mutation. A case report of targeted therapy against BRAF mutations was also presented.

Results: A cohort of 222 adenocarcinoma patients with adequate pathologic tissue samples was analyzed. The median patient age was 63 years, 68.8% of the patients were male and 68.7% were ever-smokers. The V600E BRAF mutation was detected in 4 patients (1.8%). The 222 study patients had a poorer survival outcome compared to stage III/IV adenocarcinoma patients with an EGFR mutation (median, 12 vs 67 months, P<0.001) from a recent previous study. Moreover, a 47-year-old female with a recurrent adenocarcinoma and a BRAF V600E mutation exhibited tumor regression after a fourth line therapy with dabrafenib and trametinib, targeting agents against BRAF mutations.

Conclusions: Although BRAF mutations are found in 1.8% of advanced adenocarcinoma patients without EGFR/ALK aberration, they may be able to serve as a treatment target in those patients.