Meta-analysis of the predictive value of KRAS mutations in treatment response using cetuximab in colorectal cancer

Purpose: The monoclonal antibody cetuximab that targets epidermal growth factor receptor (EGFR) has been found effective in the treatment of colorectal cancer However, mutations in exons 12 and 13 of KRAS oncogene have been reported as negative predictive factors for the treatment response using cetuximab. The purpose of this study was to conduct a meta-analysis of the published studies investigating the predictive value of KRAS mutations in the efficacy of cetuximab in patients suffering from colorectal cancer Methods: A systematic search of the literature was performed in PubMed, Medline, and Cochrane databases. Sensitivities, specificities and predictive values (negative and positive) of KRAS mutations as regards treatment response were calculated. Results: Twenty-six studies were initially found during the literature search. After thorough evaluation, 13 papers were excluded for various reasons. Therefore, 13 studies were included in the present meta-analysis. In these studies, specificities were found much higher than sensitivities. Combining the data from the 13 studies, it was found that KRAS mutations comprise a negative predictive biomarker for response to cetuximab with very high specificity (0.96; 95% CI 0.84-0.99), and low sensitivity (0.47; 95% CI 0.43-0.50). Finally, the publication bias was found statistically significant. Conclusion: The results of the present meta-analysis suggest that cetuximab should be administered only to patients with colorectal cancer who have the wild type (KRASw) oncogene. Mutations in the KRAS gene are a negative predictive factor for response to cetuximab with very high specificity and low sensitivity. The latter may very well be attributed to additional mechanisms of resistance to anti-EGFR therapies such as mutations in BRAF.