Analysis of EGFR status in metastatic colorectal cancer patients treated with cetuximab monotherapy

3595 Background: Erbitux (Cetuximab), an IgG1 monoclonal antibody, has demonstrated activity in patients with colorectal cancer (CRC), both as a single agent and in combination with irinotecan. This phase II study explored the activity of cetuximab in patients with metastatic CRC, who progressed following treatment with a fluoropyrimidine, irinotecan, and oxaliplatin. Methods: Prior to study entry, patients were screened for EGFR expression with the DakoCytomation EGFR pharmDx test kit. EGFR status was classified as undetectable, 1+, 2+, or 3+. Patients received cetuximab at an initial dose of 400 mg/m2, followed by weekly doses at 250 mg/m2, until disease progression or unacceptable toxicity. Results: Of 346 treated patients, the median number of prior regimens was 4 (range 2–9). 12% of patients achieved a PR (95% CI 8% - 15%) with a median survival of 6.6 months (95% CI 5.6–7.6 months). Conclusion: EGFR staining intensity does not appear to correlate with increased survival in patients treated with cetuximab. This appears to differ from results with erlotinib (Tarceva), which demonstrated prolonged survival in EGFR+, but not EGFR-negative patients.(Erlotinib Package Insert 2004). EGFR staining might be a more relevant determinant of activity for small molecules than for Mabs. Due to the limited size of the data set, further investigation is warranted and a clinical trial investigating EGFR undetectable patients is being conducted to determine if the trend observed in this study is maintained in a larger population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Chiron, Response Genetics, Genentech Bristol-Myers Squibb, Roche, Pfizer, Lilly, Sanofi Bristol-Myers Squibb, NCI, NIH