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

Abstract

Purpose The KRAS gene frequently mutates in colorectal cancer (CRC). Here we investigated the prognostic and predictive role of KRAS 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 KRAS mutation. Among the 190 patients who did not receive adjuvant therapy, those with KRAS 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, KRAS 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 KRAS 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 KRAS mutant tumors and is worth further investigation.

Keywords

• KRAS
• Adjuvant chemotherapy
• Colorectal cancer
• FOLFOX