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. Methods: 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. Results: 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. Conclusions: 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. PFS and overall response rate (RR) by KRAS mutation status KRAS status Median PFS (mo) Cetuximab + FOLFOX Median PFS (mo) FOLFOX Overall RR (%) Cetuximab + FOLFOX Overall RR (%) FOLFOX Wild-type 7.7 (n=61) 7.2 (n=73) HR:0.57 p=0.02 61 (n=61) 37 (n=73) p=0.01 Mutation 5.5 (n=52) 8.6 (n=47) HR:1.83 p=0.02 33 (n=52) 49 (n=47) p=0.11 HR, hazard ratio. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Serono Merck Merck, Merck Serono