An analysis of epidermal growth factor receptor (EGFR) immunohistochemistry in the MRC COIN trial has revealed that patients with KRAS wild-type advanced colorectal cancer whose disease stains ≥ 10% positive for EGFR have a progression-free survival benefit from the addition of cetuximab (Erbitux) to standard oxaliplatin-based chemotherapy. Yet < 10% EGFR-positive immunohistochemistry was not prognostic for either progression-free survival, overall survival, or overall response among patients with KRAS wild-type tumors. EGFR-positive patients with KRAS mutations also did worse on cetuximab than those who received just standard therapy. The results of the EGFR analysis of the MRC COIN trial were presented in January at the Gastrointestinal Cancers Symposium in San Francisco.¹

“Although this effect in patients with KRAS mutant disease was not statistically significant, it was a strong trend in keeping with other studies, said Richard Adams, MD, a Senior Lecturer at Cardiff University School of Medicine in the United Kingdom. The addition of cetuximab to standard therapy had little effect on the outcomes of patients with KRAS mutant tumors who were negative for EGFR, he added.

“These findings are consistent with the as yet unexplained variation of the biologic characteristics of colorectal cancer carrying the KRAS mutation,” Dr. Adams said. “EGFR-positive tumors do provide some prognostic value with progression-free survival and overall survival in univariate analysis, but this statistical significance is lost in the multivariate analysis when assessing overall survival,” he added.

Additional Insight into Prognosis

In the MRC COIN trial, 2,445 patients were randomly assigned to three arms that included treatment with oxaliplatin plus a fluoropyrimidine with or without cetuximab. EGFR immunohistochemistry was assessed for 1,621 patients—22% were EGFR-negative and 78% were EGFR-positive, and these results were balanced across the arms of the trial, Dr. Adams said. Although the study on cetuximab was negative, analyzing results in terms of EGFR biomarker status can provide additional insight into prognosis, Dr. Adams noted.

Although EGFR was not prognostic for progression-free survival within KRAS wild-type patients at the standardized cutoff point, it was prognostic at the 10% mark. The investigators’ analysis indicated that patients who had at least 10% EGFR staining had better progression-free survival outcomes (< 10% vs ≥ 10%, HR = 1.27, 95% CI = 1.07–1.52, P = .008).

Dr. Adams noted that the results of the MRC COIN analysis indicate that there could be a role for EGFR immunochemistry as a prognostic variable in patients with KRAS wild-type advanced colorectal cancer. Yet the extensive assessment of samples available in the trial suggests that the predictive value of these factors for cetuximab used in combination with chemotherapy in first-line colorectal cancer therapy does not hold true, he said. ■

Reference

1. Adams RA, James MD, Smith CG, et al: Epidermal growth factor receptor (EGFR) as a predictive and prognostic marker in patients with advanced colorectal cancer: The MRC COIN trial experience. Gastrointestinal Cancers Symposium. Abstract 359. Presented January 22, 2011.