KRAS as a predictor of poor prognosis and benefit from postoperative FOLFOX chemotherapy in patients with stage II and III colorectal cancer

Purpose: The ERAS gene frequently mutates in colorectal cancer (CRC). Here we investigated the prognostic and predictive role of ERAS mutation in patients with stage II or III CRC. Experimental design: A consecutive cohort of patients with stage II or III CRC from a single center database was studied. The association between KRAS status, adjuvant FOLFOX therapy, and 3-year disease-free survival (3-y DFS) was analyzed. Results: Of our 433 patients, 166 (38.3%) exhibited the ERAS mutation. Among the 190 patients who did not receive adjuvant therapy, those with ERAS mutation tumors had a worse 3-y DFS (hazard ratio [HR], 1.924; 95% confidence interval [CI], 1.078-3.435; P = 0.027). Among patients who received adjuvant chemotherapy, ERAS mutation was not correlated with worse 3-y DFS (HR, 1.083; 95% CI, 0.618-1.899; P = 0.781). Adjuvant chemotherapy improved 3-y DFS only among patients with KRAS mutant tumors (78.0% vs 69.2%) on multivariate analysis adjusted for age, stage, grade, site, vessel invasion, and carcinoembryonic antigen level (HR, 0.454; 95% CI, 0.229-0.901; P = 0.024). In contrast, there was no benefit of adjuvant chemotherapy in the ERAS wild-type group (84.3% vs 82.0%). Conclusions: KRAS mutation indicates poor prognosis. FOLFOX adjuvant chemotherapy benefits patients with stage II or III colorectal cancer with ERAS mutant tumors and is worth further investigation. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.