Preliminary results from a large, randomized clinical trial for patients with previously untreated recurrent or metastatic breast cancer -- cancer that has spread from the breast to other parts of the body -- show that those patients who received bevacizumab (Avastin^™) in combination with standard chemotherapy had a longer time period before their cancer progressed than patients who received the same chemotherapy without bevacizumab.

The clinical 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, Inc., South San Francisco, Calif., which manufactures bevacizumab, provided bevacizumab for the trial under the Cooperative Research and Development Agreement (CRADA) with NCI for the clinical development of bevacizumab.

The Data Monitoring Committee overseeing the trial (known as E2100)* recommended that the results of a recent interim analysis be made public because the study had met its primary endpoint of increasing progression-free survival (the amount of time patients lived without the cancer getting worse).

Preliminary results suggest that patients in the study who received bevacizumab in combination with standard chemotherapy consisting of single-agent paclitaxel had a delay in worsening of their cancer by approximately five months, on average, compared to patients treated with paclitaxel chemotherapy alone. This difference is statistically significant. Detailed results about this trial were presented on May 16, 2005, at the American Society of Clinical Oncology meeting. The results include the facts that those on bevacizumab plus standard chemotherapy had progression-free survival of 10.97 months vs 6.11 months on standard chemotherapy alone which is a 49 percent improvement in progression-free survival. There was a 28 percent response rate for those on bevacizumab plus standard chemotherapy vs. 14 percent for those on standard chemotherapy only

"This study is the first to find a benefit of anti-angiogenic therapy in patients with breast cancer and represents a major advance in the treatment of patients with metastatic disease," said Study Chair Kathy D. Miller, M.D., of the Indiana University Medical Center in Indianapolis, Ind. Anti-angiogenic drugs, also called angiogenesis inhibitors, are substances that may prevent angiogenesis, or the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor.

"Recent clinical trials have shown that anti-angiogenic drugs have a favorable impact on colon and lung cancers," said NCI Director Andrew C. von Eschenbach, M.D. "This study demonstrates that when patients with recurrent or metastatic breast cancer received bevacizumab in addition to their chemotherapy, the period of time that they lived with their cancer under control was increased. This is an important step in our journey to ultimately eliminate the suffering and death due to cancer."

A total of 722 women with recurrent or metastatic breast cancer who had not previously received systemic chemotherapy for their recurrent or metastatic disease were enrolled in this study between December 2001 and May 2004. Patients were randomized to one of the two treatment arms. One patient group received standard treatment consisting of single-agent paclitaxel. The second group received the same regimen of paclitaxel with the addition of bevacizumab.

Patients whose tumors overexpressed HER-2 were not included in the study unless they had previously received trastuzumab (Herceptin^TM) or were unable to receive trastuzumab. Also excluded were patients who had received preventive chemotherapy treatment with paclitaxel within the previous 12 months, as well as patients with a prior history of blood clots or who were on blood thinners. Serious bleeding and blood clots were rare in this study. Patients receiving the combination of paclitaxel and bevacizumab had slightly more neuropathy, or problem in peripheral nerve function (any part of the nervous system except the brain and spinal cord); abnormally high blood pressure; and proteinuria, a condition in which urine contains an abnormal amount of protein, than patients receiving paclitaxel alone. Other side effects were similar between the two treatment groups.

Bevacizumab, a humanized monoclonal antibody** that already has been approved for metastatic colorectal cancer in combination with chemotherapy, is designed to bind to and inhibit vascular endothelial growth factor (VEGF). VEGF is a protein that plays a critical role in tumor angiogenesis.

"It is noteworthy that a previous company-sponsored trial in patients who received prior chemotherapy for advanced disease did not show a benefit with bevacizumab in combination with capecitabine, a different chemotherapy agent," said JoAnne Zujewski, M.D., who heads breast cancer trials for NCI's Cancer Therapy Evaluation Program. "It is fortunate that ECOG, assisted by multiple other NCI-sponsored Cooperative Groups, persisted with this trial in patients with newly diagnosed advanced breast cancer, as the agent is clearly active in this setting."

An estimated 211,240 women will be diagnosed with breast cancer in the United States in 2005. Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer-related death in women in this country. An estimated 40,110 deaths from female breast cancer will occur in 2005 in the United States, accounting for about 15 percent of all cancer-related deaths in women in the nation.

For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4 CANCER (1-800-422-6237).

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