KRAS Status as a Predictor of Chemotherapy Activity in Patients With Metastatic Colorectal Cancer

Abstract

Background: KRAS mutations occur in 40% of colorectal cancers (CRCs), affecting the efficacy of agents targeting the epidermal growth factor receptor. However, the effect of KRAS mutation status on the activity of non-epidermal growth factor receptor-targeting chemotherapy has not been fully elucidated. The aim of the present study is to evaluate the effect of KRAS status on the activity of different chemotherapeutic regimens. Patients and Methods: A retrospective chart review of chemotherapy-treated patients with metastatic CRC with known KRAS status was undertaken. Chemotherapy effects were measured by progression-free survival, time to chemotherapy resistance, and overall survival. Analysis was performed for the different chemotherapy regimens, and according to the KRAS mutation status while adjusting for potential confounders. Results: KRAS mutations were detected in 43% of 223 patients with metastatic CRC who were treated at the Ottawa Hospital. The baseline distribution of KRAS wild-type (WT) and mutant status was similar. The median follow-up was 27.2 months. Regimens received included single agents or combinations of 2 or 3 chemotherapies. Among those treated with capecitabine-based regimens, survival was longer for patients with KRAS WT status (hazard ratio, 0.47; 95% confidence interval, 0.23-0.95; P < .0001) when compared with those with mutant status. The median overall survival was 46.7 versus 32.6 months for patients with KRAS WT versus mutant status, respectively. The time to chemotherapy resistance was also significantly longer for patients with WT status (hazard ratio, 0.49; 95% confidence interval, 0.25-0.97; P = .0398). A trend for progression-free survival did not reach statistical significance. Conclusion: Patients with KRAS WT tumors may benefit more from capecitabine-based treatments than patients with mutant status. Further research is needed to explain this data.