Activity of cetuximab in patients with colorectal cancer refractory to both irinotecan and oxaliplatin

Abstract

3510 Background: Cetuximab (Erbitux) has demonstrated activity in patients with epidermal growth factor receptor (EGFR) expressing colorectal cancer (CRC) refractory to irinotecan (CPT-11) both as a single agent and in combination with irinotecan. This phase II study was designed to explore the activity of cetuximab in patients with EGFR+ CRC refractory to both CPT-11 and oxaliplatin (ox). Cetuximab is a chimeric monoclonal antibody that binds specifically to the EGFR preventing homo and heterodimerization and signal transduction. Methods: Patients were treated with cetuximab at standard doses 400 mg/m2 loading dose over 2 hours, then 250 mg/m2 over 1 hour weekly. Results: 350 patients with EGFR + CRC who had failed both CPT-11 and ox were enrolled. Median age 59; M:F::55:45; ECOG performance status 0:1::42:57. The most commonly encountered adverse events were an acne-like skin rash (84% any grade, 5% grade 3) and fatigue/malaise (40% any grade, 9% grade 3/4). Three patients experienced a grade 3/4 allergic reaction requiring discontinuation of study treatment. Partial responses (PR) were observed in 12% of patients (28/235; 95% CI 8–17). 34% of patients had stable disease for at least 6 weeks bringing the disease control rate to 46%. Prior to an amendment to the protocol 9 patients with EGFR negative CRC were enrolled, 2 of whom had a PR. Conclusions: Cetuximab was well tolerated in this patient population and produced major objective responses in 12% of patients who had exhausted all available treatment options for metastatic colorectal cancer. This result is consistent with results reported by Saltz (ASCO 2002) and Cunningham (ASCO 2003). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems ImClone Systems ImClone Systems Bristol-Myers Squibb ImClone Systems