BETHESDA, Maryland—Data from the randomized, phase III E3200 trial show that patients with advanced colorectal cancer who were treated with bevacizumab (Avastin) in combination with the oxaliplatin (Eloxatin)-based regimen known as FOLFOX4 had a significant survival advantage, compared with patients treated with FOLFOX4 alone. The National Cancer Institute (NCI) released the results from an interim analysis at the recommendation of the trial’s data monitoring committee (DMC), after the trial monitors determined that the study had met its primary endpoint of improved overall survival.

Patients treated with bevacizumab and FOLFOX4 (oxaliplatin, fluorouracil, and leucovorin) had a median overall survival of 12.5 months vs 10.7 months for those receiving FOXFOX4 alone. The difference represented a 17% improvement in median overall survival and a 26% reduction in the risk of death for the bevacizumab arm.

"We now know that bevacizumab added to second-line chemotherapy with FOLFOX4 improves survival," said study chair Bruce J. Giantonio, MD, of the University of Pennsylvania’s Abramson Cancer Center. "With these findings, we can now more confidently expect survival for people with advanced disease to be more than double what it was just a few years ago." Dr. Giantonio said that preliminary results of the E3200 trial will be presented at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium this month.

Bevacizumab binds to and inhibits vascular endothelial growth factor (VEGF), a crucial player in tumor angiogenesis. Oxaliplatin is a novel platinum-based anticancer drug that destroys cancer cells. "The results of this study are very important for all those living with advanced colorectal cancer," said NCI director Andrew C. von Eschenbach, MD. "They provide further confirmation that a biologic agent that targets a tumor’s blood supply can prolong survival when combined with chemotherapy, even for patients who have previously received therapy for advanced disease."

NCI sponsored the 829-patient trial, which was conducted by a network of researchers led by the Eastern Cooperative Oncology Group. Accrual occurred between October 2001 and April 2003. Investigators accepted advanced colorec-tal patients previously treated with a fluorouracil-based therapy and irinotecan (Camptosar), alone or at the same time, who had advanced disease or a relapse within 6 months of adjuvant treatment.

Patients were randomized to three groups: FOLFOX4 plus bevacizumab, standard FOLFOX4 treatment only, or bevacizumab only. In March 2003, trial investigators stopped randomizing patients to the bevacizumab-only arm after the DMC found that early data indicated this group of patients might have a lower overall survival than those in the other two arms. The treatment toxicities associated with bevacizumab were consistent with previous trials in which the drug was combined with chemotherapy.