Cetuximab monotherapy significantly improves survival of patients with metastatic colorectal cancer refractory to all approved chemotherapy agents, according to an article in the November 15 issue of the New England Journal of Medicine.

The multicenter, open-label, randomized Phase III trial compared cetuximab plus best supportive care to best supportive care alone in patients whose disease had progressed through treatment with all approved chemotherapy agents, including irinotecan, oxaliplatin, 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.

"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 Systems.

The study enrolled patients with epidermal growth factor receptor (EGFR) expressing metastatic colorectal cancer 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, median survival was 6.1 months for cetuximab patients plus best supportive care versus 4.6 months for patients on supportive care alone. Treatment resulted in a significant improvement in progression-free survival versus best supportive care alone. Twenty-three patients (8.0 percent) treated with cetuximab and no patients on best supportive care alone had partial responses.

Grade 3/4 adverse events (occurring in greater than or equal to 10 percent of patients in either group) reported more frequently in the combination treatment arm compared with supportive care only arm included fatigue (33 percent versus 26 percent), other pain (16 percent versus 7 percent), dyspnea (16 percent versus 12 percent), infection without neutropenia (13 percent versus 6 percent) rash/desquamantion (12 percent versus less than1 percent), and other gastrointestinal (10 percent versus 8 percent).

Grade 3/4 infusion reactions (hypersensitivity) occurred in 5 percent of patients in the combination arm. The most common (occurring in greater than or equal to 25 percent of patients in either group) adverse events of any grade were rash/desquamation, fatigue, abdominal pain, other pain, dry skin, dyspnea, constipation, pruritus, diarrhea, vomiting, infection without neutropenia, headache, fever, insomnia, cough, other dermatology, and stomatitis.