Clinical characteristics and outcome of patients with lung cancer harboring BRAF mutations.

Abstract

BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations are identified in approximately 2% of non-small cell lung cancer (NSCLC). Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far. Here we took advantage of the French National Cancer Institute Program of systematic molecular profiling of metastatic lung cancer, to collect clinical characteristics and analyze the outcome of consecutive patients with NSCLC harboring BRAF mutations at the Lyon University Hospital laboratory between February 2012 and October 2014. Especially, we compared those variables with that of patients with EGFR-, BRAF-, KRAS-, HER2-, PIK3CA- wild-type NSCLCs. Among 2690 patients with genotyped NSCLC during the study period, BRAF mutations were identified in 80 (3%) cases, consisting of V600E substitution in 42 (53%) cases; non-V600E mutation were observed in 38 (48%) cases. Concurrent mutations were not observed in case of BRAF V600 mutation, and were identified in 5 patients with BRAF non-V600E mutations, in all cases consisting of KRAS mutations. Non-V600E mutations were more likely to be observed in smokers, as compared V600E mutations. There was no significant difference in age, histologic type, performance status, and stage at diagnosis between cases of V600E and non-V600E mutations. Overall survival did not significantly differ in BRAF wild-type, V600E, and non-V600E patients. This one of the largest series of patients with BRAF mutant NSCLC. Our clinical data suggest that BRAF mutations define specific subsets of patients with NSCLC; while their oncogenic nature is yet to be established in lung cancer, especially for non-V600E mutations, the value of BRAF mutations to predict the efficacy of targeted agents remains unclear.