Study Finds Racial Differences in BRAF/KRAS Mutation and Disease-Free Survival in Patients With Stage III Colon Cancer
- Asian patients with stage III colon cancer had lower rates of BRAF and KRAS mutations.
- Black patients with stage III colon cancer had poorer disease-free survival vs whites among patients younger than age 50 and those with N1 disease.
In a study reported in the Journal of the National Cancer Institute, Yoon et al found that among patients with stage III colon cancer in the Alliance N0147 trial, Asians had the lowest rate of BRAF/KRAS mutations and longer disease-free survival vs whites among patients with N2 disease and that blacks had poorer disease-free survival vs whites among patients younger than age 50 and those with N1 disease independent of other factors.
The Alliance N0147 trial showed that the addition of cetuximab (Erbitux) to adjuvant FOLFOX (fluorouracil, leucovorin, oxaliplatin) did not improve disease-free survival in patients with stage III colon cancer. The current study included analysis of BRAF V600E and KRAS mutations in 3,305 patients in Alliance N0147, including 2,916 white, 240 black, and 149 Asian patients. Associations of race with survival were assessed in 2,931 patients who received FOLFOX-based therapy in the trial, including 2,576 white, 218 black, and 137 Asian patients.
BRAF mutation was found in 13.9% of white patients, compared with 6.4% of blacks (P = .009) and 5.6% of Asians (P < .001). KRAS mutation was found in 44.1% of blacks, compared with 27.8% of Asians (P = .001) and 34.9% of whites (P = .07). The frequency of tumors that were both BRAF and KRAS wild-type was 66.7% among Asians, compared with 49.5% among blacks (P = .001) and 51.2% among whites (P < .001; P <. 001 overall).
The prognostic impact of race differed by age and N stage (P < .02 for interaction for both). Compared with whites, blacks had shorter disease-free survival among patients younger than age 50 (hazard ratio [HR] = 2.84, 95% confidence interval [CI] = 1.73–4.66) and those with N1 disease (HR = 1.54, 95% CI = 1.04–2.29) independent of BRAF or KRAS status and other covariates. Among patients with N2 disease, Asians had better disease-free survival than whites (HR = 0.49, 95% CI = 0.30–0.79); this effect appeared to be partly mediated by the lower BRAF mutation frequency (but not KRAS status) among Asians (mediation effect = –0.179, 95% CI = –0.434 to –0.004).
The investigators concluded, “Colon cancers from Asians have a lower rate of BRAF and KRAS mutations than blacks or whites. We report a novel interaction of race with age and N stage in node-positive disease, indicating that racial disparities in survival persist despite uniform stage and treatment in a phase III trial.”
Harry H. Yoon, MD, of Mayo Clinic, Rochester, is the corresponding author of the Journal of the National Cancer Institute article. The authors declared no conflicts of interest.
The study was supported by the National Institutes of Health and the National Cancer Institute.