Racial Differences in KRAS/BRAF Mutation Rates and Survival in mCRC

Conference Correspondent - ASCO 2014 - Colorectal and Head & Neck Cancer

It is unknown if racial disparities in mCRC persist after controlling for molecular or clinical variables and treatment. In a study of 3305 patients with stage III mCRC treated with FOLFOX +/- cetuximab, KRAS/BRAF mutations were determined and stratified according to race—Asian, black, or white (Yoon HH, et al. ASCO 2014. Abstract 3536). KRAS-mutant (mut) frequency in tumors from whites was twice that of tumors from blacks or Asians (P <.005), whereas BRAF-mut tumors were most common in blacks (P <.005). KRAS/BRAF–wild-type (WT) rates were highest in tumors from Asians (P <.005). Compared with whites, tumors from blacks were more likely to be N1 (rather than N2) and low grade (rather than high grade), and tumors from Asians were more likely to be distal (all P <.003). Blacks had shorter disease-free survival (DFS) than whites among N1 patients, but Asians had longer DFS among N2 patients, independent of KRAS/BRAF mutation status. These are the first data to show that Asians have a significantly lower rate of KRAS/BRAF mutations than whites or blacks, and that racial disparities persist despite uniform staging and similar treatment in a phase 3 clinical trial. The implication of these data is to add another layer of complexity in personalizing treatment for stage III mCRC, to be based on race.