Companion Diagnostics and Cancer Biomarkers Epidermal Growth Factor–like Domain 7 Predicts Response to First-Line Chemotherapy and Bevacizumab in Patients with Metastatic Colorectal Cancer

Thenumber of approved antiangiogenic drugs is constantly growing andemphasizes theneed forpredictive biomarkers. The aimof this studywas to analyze thepredictive value of epidermal growth factor–like domain 7 (EGFL7) andmicroRNA-126 (miR126) tofirst-line chemotherapy combinedwith bevacizumab, inpatientswith metastatic colorectal cancer (mCRC). A total of 158 patients from two different, but comparable, cohorts were included. Analyses were performed on tumor tissue from the primary tumor either based on a whole-tumor resection or an endoscopic biopsy. EGFL7was analyzedby immunohistochemistry (IHC) andmiR126by in situ hybridization (ISH). Both biomarkers were quantified by image-guided analyses. Endpoints were response rate (RR) and progression-free survival (PFS). The EGFL7 vessel area (VA) in tumor resections was closely related to treatment responsewith amedianEGFL7VAin respondingpatientsof 4 [95%confidence interval (CI), 4–6] comparedwith 8.5 (95%CI, 7–11) in nonresponders,P1⁄4 0.0008. This difference translated into a borderline significant difference in PFS (P 1⁄4 0.06). Furthermore, a significant relationship between high EGFL7 VA and KRASmutationwas detected (P1⁄4 0.049). The results showedno significant relationship between themiR126VA and the clinical endpoints. Our study suggests a predictive value of EGFL7 in regard to first-line chemotherapy and bevacizumab in patients with mCRC and supports the mechanism of a dual blocking of the vascular endothelial growth factor-A and EGFL7 axis in this setting. Mol Cancer Ther; 13(9); 2238–45. 2014 AACR.