ERCC-1 gene expression levels and outcome to FOLFOX chemotherapy in patients enrolled in CONFIRM1 and CONFIRM2

Abstract

4131 Background: ERCC-1 is a nucleotide excision repair gene associated with DNA repair of DNA adducts induced by platinum based chemotherapy. ERCC-1 mRNA levels have been shown to predict outcome in patients with NSCLC, gastric, bladder and ovarian cancer when treated with platinum based chemotherapy. We tested whether ERCC-1 gene expression is associated with outcome in patients with metastatic colon cancer treated with FOLFOX in first and second line treatment with or without PTK/ZK Methods: 191 formalin fixed paraffin embedded (FFPE) tumor samples from patients enrolled in CONFIRM 1 and CONFIRM2 were analyzed. 85 patients from CONFIRM1 (42 pts treated with FOLFOX, 43 pts with FOLFOX/PTK/ZK) and 106 from CONFIRM2 (54 pts treated with FOLFOX, 52 with FOLFOX/PTK/ZK). FFPE tissues were dissected using laser-captured microdissection and analyzed for ERCC-1 mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference gene (beta-actin). Results: Low ERCC-1 gene expression was associated with better response to FOLFOX chemotherapy in first and second line chemotherapy (p=0.047, p=0.054). ERCC-1 gene expression was associated with overall survival in first and second line FOLFOX chemotherapy (p=0.014, p=0.14). pts with high ERCC-1 did not have any benefit from FOLFOX chemotherapy, but had benefit from treatment of FOLFOX+PTK/ZK, this drug and ERCC1 expression interaction was statistically significant (p=0.015). Conclusions: These results suggest that ERCC-1 gene expression levels predict response and overall survival in patients with metastatic colorectal cancer enrolled in CONFIRM1 and 2. ERCC-1 gene expression levels may allow the selection of patients who benefit likely from FOLFOX chemotherapy. We could show for the first time that VEGFR TKI efficacy may depend on ERCC-1 status. Further studies are warranted to study this unexpected interaction. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Novartis, Response Genetics, Inc Bristol-Myers Squibb, Genentech, ImClone, Merck, Pfizer, Response Genetics, Inc Novartis, Response Genetics, Inc Genentech, Merck, Pfizer, Roche, sanofi-aventis Dhont Family Foundation, NCI, NIH, Novartis