533P - Somatic K-Ras Mutation is Predictive in Colorectal Cancer, but is it Prognostic? A Systematic Review and Meta-Analysis

Abstract

ABSTRACT Background Consistent data from retrospective molecular analysis performed in multiple phase 3 Randomized controlled trials (RCTs) have established that somatic KRAS mutation (K-RAS-mt) is a strong predictor of non-response to anti-epidermal growth factor receptor antibody (anti-EGFR) therapy in colorectal cancer. However, K-RAS's role as a prognostic marker remains undefined. We performed a systematic review and meta-analysis to determine the prognostic significance of somatic K-RAS mutation. Methods We searched MEDLINE, EMBASE, and CENTRAL databases, ESMO and ASCO meeting proceedings for Phase 3 RCTs in colorectal cancer for which retrospective molecular analysis of K-RAS mutation was performed on archival patient samples. Studies were pooled according to setting of treatment (adjuvant, 1st line metastatic, refractory). Meta-analysis was performed using random-effects model. The outcomes of interest were disease-free survival in the adjuvant setting and overall survival (OS) for advanced disease. Results 14 Phase 3 trials which enrolled 18,991 patients were identified, of whom 13,143 had K-RAS status ascertained (69.2% range: 48%-100%) In pooled data of patients who did not receive anti-EGFR therapy and had K-RAS status ascertained, patients with K-RAS-wt patients had better survival outcomes compared to K-RAS-mt patients. In the adjuvant setting (Disease Free Survival HR 0.75 95% CI: 0.66-0.87, p Conclusion Beyond being a predictive marker of non-response to EGFR antibodies, among patients with early stage, 1st line metastatic and refractory colorectal cancer who do not receive anti-EGFR therapy, K-RAS is a negative prognostic marker. Disclosure All authors have declared no conflicts of interest.