Amphiregulin Expression Is a Predictive Biomarker for EGFR Inhibition in Metastatic Colorectal Cancer: Combined Analysis of Three Randomized Trials

Stahler, Arndt; Stintzing, Sebastian; Modest, Dominik P.; Ricard, Ingrid; Giessen-Jung, Clemens; Kapaun, Christine; Ivanova, Boryana; Kaiser, Florian; Fischer von Weikersthal, Ludwig; Moosmann, Nicolas; Schalhorn, Andreas; Stauch, Martina; Kiani, Alexander; Held, Swantje; Decker, Thomas; Moehler, Markus; Neumann, Jens; Kirchner, Thomas; Jung, Andreas und Heinemann, Volker (2020): Amphiregulin Expression Is a Predictive Biomarker for EGFR Inhibition in Metastatic Colorectal Cancer: Combined Analysis of Three Randomized Trials. In: Clinical Cancer Research, Bd. 26, Nr. 24: S. 6559-6567

Abstract

Purpose: Amphiregulin (AREG) and epiregulin (EREG) arc ligands of EGFR. Predictive information for anti-EGFR treatment in metastatic colorectal cancer (mCRC) was observed, but data for other agents is limited. Experimental Design: Ligand mRNA expression;RAS, BRAE PIK3CA mutations;and EGFR expression were assessed by qRT-PCR, pyrosequencing, and IHC, respectively, in mCRC tumor tissue of patients participating in the randomized controlled trials FIRE-1, CIOX, and FIRE-3. Normalized mRNA expression was dichotomized using median and third quartile. Overall (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method including univariate and multivariate Cox regression analyses. Penalized spline regression analysis tested interaction of mRNA expression and outcome. Results: Off 688 patients with available material, high AREG expression was detected in 343 (>median) and 172 (>3rd quartile) patients. High AREG expression was associated with significantly higher OS [26.2 vs. 21.5 months, HR = 0.80;95% confidence interval (CI), 0.68-0.94;P = 0.007], PFS (10.0 vs. 8.1 months, HR = 0.74;95% CI, 0.63-0.86;P 0.001), and objective response rate (63.1% vs. 51.6%, P = 0.004) compared to low expression at both threshold values. This effect remained significant in multivariate Cox regression analysis (OS: P = 0.01, PFS: P = 0.002). High AREG mRNA expression interacted significantly with the efficacy of cetuximab compared with bevacizumab (OS: P = 0.02, PFS: P = 0.04) in RAS WT mCRC. Conclusions: High AREG mRNA expression is a favorable prognostic biomarker for mCRC which interacted significantly with efficacy of anti-EGFR treatment.

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