NEW ORLEANS-Cetuximab (Erbitux), a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), produced major objective responses in 12% of patients who had exhausted all available treatments for metastatic colon cancer. This was the principal conclusion of a phase II trial presented by Heinz- Josef Lenz, MD, Division of Medical Oncology, University of Southern Cal- ifornia, at the 40th Annual Meeting of the American Society of Clinical Oncology (abstract 3510). The logic for assessing the effect of cetuximab(Drug information on cetuximab) treatment derives from clinical data showing that more than two-thirds of patients with advanced colorectal cancer are positive for EGFR expression. This expression is, in turn, indicative of increased probability of metastasis and poor prognosis. By binding to the extracellular domain of the EGFR, cetuximab exerts a variety of effects that impede the progress of the cancer, including inhibition of cell growth and survival, metastasis, and angiogenesis. Prior work had shown that cetuximab monotherapy resulted in a 9% response rate with irinotecan(Drug information on irinotecan) (Camptosar)-refractory, EGFR-expressing metastatic colorectal cancer (Saltz et al: J Clin Oncol 22:1201-1208, 2004). The current trial focused on a patient population that had been even more intensively treated, with disease that progressed after either two chemotherapy regimens for metastatic disease or adjuvant therapy plus one chemotherapy regimen. The failed chemotherapy regimens had to have included irinotecan, oxaliplatin(Drug information on oxaliplatin) (Eloxatin), and a fluoropyrimidine. In all, 346 patients were enrolled, all but nine of whom had tumors that were positive for EGFR by immunohistochemistry; the EGFR-negative patients had been enrolled prior to a protocol change. Patients were given an initial infusion of 400 mg/m2, followed by weekly treatments at 250 mg/m2, continuing until either disease progression or the development of unacceptable toxicity. Median duration of treatment was 9 weeks (range, 1 to 56 weeks). Response and Toxicity Objective responses, as assessed by an independent review committee, were seen in 40 patients (11.6%); all responses were partial. A further 110 patients (31.8%) were classified as having stable disease, giving a disease control rate of 43.4%. Median survival was 6.7 months. Among the nine patients whose tumors were classified as EGFR negative, there was one partial response and three cases of stable disease; in brief, their response rate mirrored that of the EGFR-positive population. Toxicity was acceptable, with principal adverse events including fatigue, acneiform rash, nausea/vomiting, diarrhea, mucositis/stomatitis, and infusion reactions. The great majority of these were not severe, Dr. Lenz said, with fatigue being the only adverse event that occurred with a severity of grade 3-4 in as many as 10% of patients. EGFR gene sequence analysis was performed in 35 cases, including 18 showing a partial response, eight with stable disease, and nine with progressive disease. Only two mutations were found, both in patients with stable disease. All cases of partial responses as well as progressive disease were wild type. Thus, while the sample size was small, there did not appear to be any differential effect of the antibody on tumors that expressed mutant receptors. The authors concluded that cetuximab was well tolerated and, with a response rate of approximately 12%, offers hope to a class of patients for whom there are very few options. The similarity between response rates among EGFR-negative and EGFRpositive patients suggests that there is no straightforward correlation between efficacy and degree of EGFR expression.