Preliminary results from a large, randomized clinical trial for patients with previously untreated advanced non-squamous, non-small cell lung cancer show that those patients who received bevacizumab (Avastin™) in combination with standard chemotherapy lived longer 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. 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 E4599)* recommended that the results of a recent interim analysis be made public because the study had met its primary endpoint of improving overall survival. Researchers found that patients in the study who received bevacizumab in combination with standard chemotherapy (a treatment regimen of paclitaxel and carboplatin) had a median overall survival of 12.5 months compared to patients treated with the standard chemotherapy alone, who had a median survival of 10.2 months. This difference is statistically significant. Detailed results from this trial were presented at a press briefing at the American Society of Clinical Oncology Annual Meeting (ASCO) in Orlando, Fla., on May 13, 2005. Specifically, it was noted that patients on bevacizumab in combination with standard chemotherapy demonstrated a higher response rate (27 percent vs. 10 percent) and a longer time until the cancer progressed (6.4 months vs. 4.5 months) than those on standard chemotherapy alone.

"The exciting results of this randomized study reveal, for the first time, an improvement in survival with the addition of a molecularly targeted agent to standard chemotherapy in this patient population," said Study Chair Alan B. Sandler, M.D., of the Vanderbilt University Medical Center in Nashville, Tenn.

"This study demonstrates that mechanistic-based interventions such as angiogenesis inhibitors are making important contributions in improving cancer outcomes," said NCI Director Andrew C. von Eschenbach, M.D. "In combination with standard therapies, they can be used for a variety of cancers, leading to increased patient survival."

A total of 878 patients with advanced non-squamous, non-small cell lung cancer (NSCLC) who had not previously received systemic chemotherapy were enrolled in this study between July 2001 and April 2004. Patients were randomized to one of the two treatment arms. One patient group received standard treatment -- six cycles of paclitaxel and carboplatin. The second group received the same six-cycle chemotherapy regimen with the addition of bevacizumab, followed by bevacizumab alone until disease progression.

Patients with squamous cell carcinoma of the lung were not included in the study because previous clinical experience suggested that patients with this particular type of NSCLC had a higher risk of serious bleeding from the lung after bevacizumab therapy. Patients with a prior history of frank hemoptysis (coughing up blood) were also not enrolled on the trial.

The most significant adverse event observed in this study was life-threatening or fatal bleeding, primarily from the lungs. This occurred infrequently, but was more common in the patient group that received bevacizumab in combination with chemotherapy than in the patient group that received only chemotherapy. A fuller description of side effects observed in this trial were presented at the ASCO press briefing as well. These included information that both treatment regimens were well-tolerated, with the most common side-effects being low white blood cell counts (24 percent on bevacizumab vs. 16 percent on standard chemotherapy), blood clots (3.8 percent vs. 3.0 percent), and bleeding (4.1 percent vs. 1.0 percent). Patients on bevacizumab had a 1.2 percent chance of life-threatening or fatal bleeding, primarily from the lungs, compared to a zero percent chance on standard chemotherapy.

Bevacizumab, a humanized monoclonal antibody**, is designed to bind to and inhibit vascular endothelial growth factor (VEGF). VEGF is a protein that plays a critical role in tumor angiogenesis, the formation of new blood vessels to the tumor.

"This trial represents another step in a series of recent important advances in treatment for patients with advanced lung cancer," said James H. Doroshow, M.D., director of NCI's Division of Cancer Treatment and Diagnosis and leader of NCI's Clinical Trials Working Group. "Important progress continues to be made by targeting molecular pathways critical to the growth and survival of cancer cells. It is through better understanding of these molecular processes that significant advances will be made in the treatment of this disease."

An estimated 172,570 people will be diagnosed with lung cancer in the United States in 2005. Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer-related death in both men and women in this country. An estimated 163,510 deaths from lung cancer will occur in 2005 in the United States, accounting for about 29 percent of all cancer-related deaths in the nation.

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