American Association for Cancer Research
10780432ccr202748-sup-247306_2_supp_6519247_qfk60m.pdf (60.03 kB)

eTable 1 from Amphiregulin Expression Is a Predictive Biomarker for EGFR Inhibition in Metastatic Colorectal Cancer: Combined Analysis of Three Randomized Trials

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journal contribution
posted on 2023-03-31, 22:06 authored by Arndt Stahler, Sebastian Stintzing, Dominik P. Modest, Ingrid Ricard, Clemens Giessen-Jung, Christine Kapaun, Boryana Ivanova, Florian Kaiser, Ludwig Fischer von Weikersthal, Nicolas Moosmann, Andreas Schalhorn, Martina Stauch, Alexander Kiani, Swantje Held, Thomas Decker, Markus Moehler, Jens Neumann, Thomas Kirchner, Andreas Jung, Volker Heinemann

Normalized AREG expression according to baseline characteristics.



Amphiregulin (AREG) and epiregulin (EREG) are ligands of EGFR. Predictive information for anti-EGFR treatment in metastatic colorectal cancer (mCRC) was observed, but data for other agents is limited. Ligand mRNA expression; RAS, BRAF, 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. Of 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. High AREG mRNA expression is a favorable prognostic biomarker for mCRC which interacted significantly with efficacy of anti-EGFR treatment.