KRAS Mutation as a Biomarker for Survival in Patients with Non-Small Cell Lung Cancer, A Meta-Analysis of 12 Randomized Trials

Abstract

<b>Background:</b> Because there is no clear consensus for the prognostic implication of KRAS mutations in patientswith non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to drawa more accurate conclusion. Materials and <br/><b>Methods</b>: A systematic computer search of articles from inception toMay 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articlesand extraction of data were independently performed by two authors. <br/><b>Results</b>: Our analysis was based onthe endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS)comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations.In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) andPFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC.According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS andPFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However,the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treatedwith chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643).<br/><b>Conclusions</b>: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLCbut not for those treated with chemotherapies integrating cetuximab.