The randomized Phase III study of Avastin (bevacizumab)
was conducted by Genentech and Roche with second-line metastatic colorectal cancer patients.

26% Reduction in Risk of Death

An interim analysis demonstrated that patients receiving Avastin plus FOLFOX4 had a 26 percent reduction in the risk of death, a hazard ratio of 0.74, compared to patients who received FOLFOX4 alone. Median survival for patients receiving Avastin plus FOLFOX4 was 12.5 months, compared to 10.7 months for those receiving FOLFOX4 alone, a 17 percent improvement.

A preliminary assessment of the safety profile suggested that Avastin could be combined safely with FOLFOX4 and adverse events observed in this study were consistent with other clinical trials in which Avastin was combined with chemotherapy.

The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG). Genentech provided Avastin for the trial under the Cooperative Research and Development Agreement (CRADA) with the NCI for the clinical development of Avastin. According to ECOG, preliminary study results will be presented during the ASCO Gastrointestinal Cancers Symposium, January 27-29, 2005, in Hollywood, Florida.

Benefits Shown for 1st and 2nd Line Metastatic Colorectal Cancer

"Avastin is the first and only targeted therapy to demonstrate improvements in survival in both first- and second-line metastatic colorectal cancer," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer.

"This is the first Phase III study to evaluate Avastin in combination with an oxaliplatin-based chemotherapy regimen in patients with metastatic colorectal cancer. This study provides additional evidence that adding Avastin to chemotherapy results in a significant survival benefit for patients with either untreated or relapsed metastatic colorectal cancer," Barron said. "We plan to share these Phase III results with the FDA to discuss the filing of a supplemental Biologics License Application for this combination in this setting of metastatic colorectal cancer."

This Phase III study was a randomized, controlled, multicenter trial that enrolled 829 patients with advanced colorectal cancer who had previously received a fluorouracil-based therapy and irinotecan, either alone or concurrently, for advanced disease or if their disease had relapsed within six months of concluding adjuvant treatment with these chemotherapy agents.

Randomization Suspended on Positive Results

The patients enrolled in this trial were randomized to receive treatment with the FOLFOX4 regimen with or without Avastin. Randomization to a third arm of the study evaluating single-agent Avastin was suspended in March 2003 on the recommendation of the Data Monitoring Committee overseeing the study when review of early results suggested that overall survival for patients in that group might be lower compared to that of patients treated on the other two arms. Results from this treatment arm have not yet been disclosed.

A preliminary assessment of the safety profile suggested that Avastin could be combined safely with FOLFOX4 and treatment toxicities observed in this study were consistent with adverse events observed in other clinical trials in which Avastin was combined with chemotherapy. Adverse events included neuropathy attributed to FOLFOX4 and hypertension, managed with oral medications, and bleeding attributed to Avastin(1).