Validation of miR-31-3p Expression to Predict Cetuximab Efficacy When Used as First-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer

Purpose: MiR-31-3p expression has been shown to be associated with response to anti-EGFR therapy. We investigated the predictive role of this biomarker in the FIRE-3 study population, including its ability to differentiate outcomes between patients receiving anti-EGFR and anti-VEGF therapy. Experimental Design: MiR-31-3p expression was measured in primary tumors obtained from 340 patients with RAS WT mCRC enrolled in the FIRE-3 Trial. This included 164 patients randomized to receive FOLFIRIplus cetuximab( FOLFIRI+Cetux) and 176 to FOLFIRIplus bevacizumab( FOLFIRI+Beva). Patients were divided into subgroups defined by low or high miR-31-3p expression using a prespecified cut-off and by treatment arm. Analyses were performed to assess treatment efficacy by subgroup. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier curves and Cox regression models. Investigator-assessed objective response (iOR), early tumor shrinkage at 6 weeks (ETS), and centrally reviewed objective response (cOR) were analyzed using logistic regression models. The predictive value of miR-31-3p expression level was assessed through a treatment interaction test using multivariate models adjusted for potential confounding factors. Results: Low miR-31-3p expressers benefited from cetuximabcompared with bevacizumabfor PFS [HR, 0.74; 95% confidence interval (CI), 0.55–1.00; P = 0.05], OS (HR, 0.61; 95% CI, 0.41–0.88; P P P P P = 0.03), OS ( P = 0.05), iOR ( P = 0.02), ETS ( P = 0.04), and cOR ( P Conclusions: MiR-31-3p expression level was validated as a predictive biomarker of cetuximabtherapy efficacy for patients with RAS WT mCRC. Clin Cancer Res; 1–8. ©2018 AACR.