Functional SNPs in vascular endothelial growth factor (VEGF-A) and overall survival (OS) in bevacizumab-treated patients with metastatic colorectal cancer (mCRC).

3594 Background: Functional SNPs in VEGF-A are prognostic for OS in several malignancies, but not described definitively in mCRC. In bevacizumab-treated patients with advanced breast cancer, VEGF -2578AA and -1154A were predictive of OS—the latter SNP reported in a recent mCRC series as well. We examined the association between five functional VEGF-A SNPs and OS in a large cohort of bevacizumab-treated patients with mCRC. Methods: 403 patients with mCRC treated from 2004-2010 were included in a retrospective analysis. DNA extraction, genotyping, and SNP evaluation were performed according to standard protocols. Survival was calculated from the time of Stage IV diagnosis until death. Data were censored as of 12/31/2010. Results: There were 279 deaths in this group of 403 patients (69%). Median age was 55.7 (24-86 y), and 54% of patients were male. Age, sex, race, tumor grade, chemotherapies, and curative surgery (metastatectomy to negative margins) were considered. Significant clinical predictors of OS in univariate Cox modeling were cetuximab treatment [HR=1.46; 95% CI 1.13-1.88; p=0.0014], irinotecan treatment [HR=2.10; 1.32-3.35; p<0.001], and curative surgery [HR=0.36; 0.25-0.75; p<0.001]. Significant negative interaction was found between both cetuximab and irinotecan and curative surgery, and in modeling that included this interaction, only surgery remained predictive. In multivariate analysis, no association was found between VEGF-A and OS (Table). Conclusions: There was no association between five functional VEGF-A SNPs and OS in this large bevacizumab-treated mCRC cohort. [Table: see text]