A study of Bevacizumab ( Avastin ) plus Paclitaxel chemotherapy in first-line metastatic breast cancer met its primary efficacy endpoint of improving progression-free survival, compared to chemotherapy alone.

Results from an interim analysis of this study showed that patients receiving Bevacizumab plus Paclitaxel doubled the duration of surviving without cancer progression compared to Paclitaxel alone ( or a hazard ratio of 0.50, which is equivalent to a 50 percent reduction in the risk of cancer progression ).

Median progression-free survival was 11 months for patients treated with Bevacizumab plus chemotherapy, compared to six months for patients treated with chemotherapy alone.

At this interim analysis, a 49 percent improvement in the secondary endpoint of overall survival ( or a hazard ratio of 0.67, which is the equivalent of a 33 percent reduction in the risk of death ) was observed.

Survival data continue to mature. In patients with measurable disease, the overall response rate was 28 percent ( 93/330 ) in the Avastin plus chemotherapy arm, a 100 percent increase over the 14 percent ( 45/316 ) observed in the chemotherapy alone arm.

" This is the first successful study to show that the scientific approach of attacking a tumor's blood supply by inhibiting angiogenesis can result in improved outcomes for women with first-line metastatic breast cancer, and the study is particularly important given the magnitude of the improvement seen in progression-free survival, the study's primary endpoint," said Kathy D. Miller, of Indiana University and principal investigator for the study.

The trial was sponsored by the National Cancer Institute ( NCI ), part of the National Institutes of Health ( NIH ), under a Cooperative Research and development Agreement between NCI and Genentech, and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG).

This Phase III study was a randomized, controlled, multicenter trial that enrolled 722 women with previously untreated metastatic breast cancer.
The patients enrolled in this trial were randomized to receive treatment with Paclitaxel with or without Avastin.
Patients with HER2-positive metastatic breast cancer were not enrolled in the study unless they had received prior treatment with Herceptin ( Trastuzumab ) or were unable to receive treatment with Herceptin.
Patients who had received adjuvant Paclitaxel within the previous 12 months and patients with a prior history of blood clots or who were receiving blood thinners were also excluded from the study.

Bevacizumab is a therapeutic antibody designed to inhibit Vascular Endothelial Growth Factor ( VEGF ), a protein that plays an important role in tumor angiogenesis and maintenance of existing tumor vessels.

A preliminary assessment of safety showed that Grade 3/4 adverse events that occurred more often in the Avastin arm included neuropathy, hypertension and proteinuria.
Neuropathy, which is known to be associated with duration of Paclitaxel therapy, occurred in 21 percent of patients in the Avastin plus chemotherapy arm and in 14 percent of patients in the chemotherapy alone arm.
Hypertension occurred in 13 percent of patients treated with Avastin plus chemotherapy and in no patients who received chemotherapy alone.
Proteinuria occurred in 2 percent of patients in the Avastin plus chemotherapy arm compared to no patients in the chemotherapy alone arm.
One patient in the Avastin plus chemotherapy arm developed symptomatic congestive heart failure ( CHF ).
Additional adverse events were similar between the two treatment arms.
Serious bleeding and blood clots were rare in this study.

According to the American Cancer Society, an estimated 211,240 women will be diagnosed with breast cancer and approximately 40,000 women will die of the disease in the United States in 2005.
Breast cancer is the most prevalent form of cancer among women in the United States.

Source: 41st Annual Meeting of the American Society of Clinical Oncology ( ASCO ), 2005


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