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

Laurent-Puig, Pierre; Grisoni, Marie-Lise; Heinemann, Volker; Liebaert, Francois; Neureiter, Daniel; Jung, Andreas; Montestruc, Francois; Gaston-Mathe, Yann; Thiebaut, Raphaeele und Stintzing, Sebastian (2019): Validation of miR-31-3p Expression to Predict Cetuximab Efficacy When Used as First-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer. In: Clinical Cancer Research, Bd. 25, Nr. 1: S. 134-141

Abstract

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 FOLFIRI plus cetuximab (FOLFIRI+Cetux) and 176 to FOLFIRI plus 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 cetuximab compared with bevacizumab for 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 < 0.01), iOR (OR, 4.0;95% CI, 1.9-8.2;P < 0.01), ETS (OR, 4.0;95% CI, 2.1-7.7;P < 0.01 and cOR (OR, 4.9;95% CI, 2.3-10.5;P < 0.01) in multivariate analyses. There was no difference in outcomes for high expressers between treatment arms. MiR-31-3p expression level was predictive of treatment effect for PFS (P = 0.03), OS (P = 0.05), iOR (P = 0.02), ETS (P = 0.04), and cOR (P < 0.01). Conclusions: MiR-31-3p expression level was validated as a predictive biomarker of cetuximab therapy efficacy for patients with RAS WT mCRC.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1078-0432
• Sprache: Englisch