KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: The OPUS experience.

4000 Background: Efficacy analyses of the randomized phase II OPUS trial have previously failed to show significant improvements in progression-free survival time (PFS) or overall response, although a significantly higher response rate was achieved in patients with good performance status (ECOG 0/1) and a significantly higher curative surgery rate for cetuximab added to FOLFOX versus FOLFOX alone in the first-line treatment of mCRC was observed. KRAS mutation status has been related to the efficacy of anti-epidermal growth factor receptor (anti-EGFR) targeted therapies in different cancer models. Efficacy analyses have been repeated to evaluate the influence of KRAS mutation status in first-line patients treated with standard therapy, with or without cetuximab, under controlled study conditions.,Genomic DNA was isolated from archived tumor material. The KRAS mutation status of codons 12/13 was determined using a sensitive, quantitative PCR-based assay. Best overall response and PFS time (IRC evaluation) are presented by KRAS mutation status.,In general, the population with tissue available for KRAS analysis (n=233) was representative of the overall intention- to-treat population (n=337) in terms of demographic and efficacy parameters. KRAS mutations were detected in 42% (99/233) of evaluable samples.,These data suggest that the benefit from addition of cetuximab to standard treatment is higher for the population with wild-type KRAS. For patients with KRAS mutations, no benefit could be shown of adding cetuximab to FOLFOX in this study. [Table: see text] [Table: see text].