Use of amphiregulin and epiregulin mRNA expression in primary tumors to predict outcome in metastatic colorectal cancer treated with cetuximab

Autor: H. Prenen, B. Jacobs, W. De Roock, R. Van Oirbeek, B. Biesmans, J. De Schutter, S. Fieuws, P. Laurent-Puig, E. Van Cutsem, S. Tejpar
Rok vydání: 2009
Předmět:
Zdroj: Journal of Clinical Oncology. 27:4019-4019
ISSN: 1527-7755
0732-183X
Popis: 4019 Background: To study the power of two epidermal growth factor receptor (EGFR) ligands, epiregulin (EREG) and amphiregulin (AREG) expression in primary tumors to predict the outcome in patients with chemorefractory metastatic colorectal cancer (cmCRC) treated with the combination of cetuximab plus irinotecan. Methods: Gene expression measurements and KRAS mutation analysis were performed on archival formalin-fixed paraffin-embedded primary tumors of 220 cmCRC patients. Response was measured using RECIST criteria. The relation between ligand expression levels and outcome was evaluated using logistic regression for response and Cox regression for survival data. ROC analysis was performed for response and survival data. Confidence intervals (CI) for the performance indices were obtained with a non-parametric bootstrap procedure. Findings were externally validated on a series of 67 samples treated in a similar setting. Results: In KRAS wild-type (WT) patients, there was a significant association between log-transformed ligand expression and response (EREG: Odds ratio for objective response 1.90 (p=0.0005, 95%CI:1.27–2.83), c-index=0.681; AREG: Odds ratio for objective response: 1.82 (p=0.0017, 95%CI:1.22–2.72), c-index=0.673). In a Cox- regression model log-transformed ligand expression was significantly associated to progression-free survival (PFS) and overall survival (OS) (EREG: hazard ratio (HR) for PFS: 0.61 (pτ-index=0.696; AREG: HR for PFS: 0.60 (95%CI:0.50–0.74), cτ-index=0.671; EREG: HR for OS: 0.61 (pτ-index=0.667; AREG: HR for OS: 0.65 (pτ-index=0.642). There was no predictive power of ligand expression in KRAS mutant patients. Conclusions: Expression of EGFR ligands in primary tumors significantly predicts favorable outcome in KRAS WT cmCRC treated with cetuximab and irinotecan. [Table: see text]
Databáze: OpenAIRE
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