A multicenter, open-label, randomized phase III trial recently published in the New England Journal of Medicine (357:2040-2048, 2007) demonstrated that cetuximab(Drug information on cetuximab) (Erbitux) as a single agent significantly improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to approved chemotherapy agents. The study compared cetuximab plus best supportive care (BSC) to BSC alone in patients with mCRC whose disease had progressed through treatment with all approved chemotherapy, including irinotecan(Drug information on irinotecan) (Camptosar), oxaliplatin(Drug information on oxaliplatin) (Eloxatin), and fluoropyrimidines.

The independent study, conducted by the National Cancer Institute of Canada Clinical Trials Group in collaboration with the Australasian Gastro-Intestinal Trials Group, involved 572 patients and demonstrated that treating patients with cetuximab monotherapy plus BSC significantly increased overall survival compared to BSC alone. BSC included palliative therapies designed to alleviate pain and treat other effects caused by mCRC.

"This is the first time an antibody used as a single agent in colorectal cancer has demonstrated an overall survival benefit. These outcomes add to the growing body of evidence supporting the significant clinical benefits of Erbitux," said Eric K. Rowinsky, MD, chief medical officer and senior vice president of ImClone, the drug's manufacturer.

Study Design

The study enrolled patients with epidermal growth factor receptor (EGFR)-expressing mCRC who had been previously treated. Cetuximab was administered at the recommended dose and schedule: 400 mg/m² initial dose, followed by 250 mg/m² weekly until disease progression or unacceptable toxicity.

In this study, the median survival was 6.1 months for patients treated with cetuximab plus BSC vs 4.6 months for patients on BSC alone (hazard ratio [HR] = 0.77, P = .005). Treatment with cetuximab monotherapy resulted in a significant improvement in progression-free survival vs BSC alone (HR = 0.68, P < .001). A total of 23 patients (8.0%) treated with cetuximab and no patients on BSC alone had partial responses (P < .001).

Grade 3/4 adverse events (occurring in at least 10% of patients in either group) reported more frequently in the cetuximab-plus-BSC treatment arm compared with the BSC-only arm included fatigue (33% vs 26%), other pain (16% vs 7%), dyspnea (16% vs 12%), infection without neutropenia (13% vs 6%), rash/desquamantion (12% vs < 1%), and other gastrointestinal events (10% vs 8%).