Avastin filed with FDA in US for treatment of women with advanced breast cancer

Roche and Genentech announced today that they have filed Avastin (bevacizumab) in the US for the first line treatment of women with metastatic (advanced) breast cancer. Breast cancer is the leading cause of cancer death worldwide in women.

"The addition of Avastin to chemotherapy as a primary treatment for metastatic breast cancer doubled the time that women lived without their disease advancing compared to patients who received chemotherapy alone." said Eduard Holdener, Head of Roche Pharmaceuticals Development. "Breast cancer is now the third type of cancer where Avastin has shown a significant survival benefit. This submission marks an important milestone in our ongoing efforts to develop innovative therapies for breast cancer patients and to address unmet medical needs."

The supplemental Biologics License Application (sBLA) has been submitted to the US Food and Drug Administration (FDA) for use of Avastin in combination with standard chemotherapy (taxanes) for the first-line treatment of women with metastatic breast cancer. The submission is based on the impressive results of the pivotal E2100 Phase III trial which shows that, patients receiving Avastin plus paclitaxel had a median progression-free survival (PFS) of more than a year while patients receiving paclitaxel alone had a median PFS of approximately six months. A Marketing Authorisation Application (MAA) will be filed with the European Authorities later this year.

More than one million women are diagnosed with breast cancer each year worldwide and eight to nine percent of women are expected to develop breast cancer during their lifetime. Breast cancer is the leading cause of cancer death in women worldwide under the age of 55, claiming more than 372,000 lives each year.

Avastin is the first and only anti-angiogenic agent to have demonstrated improved overall and/or progression-free survival in the three important types of cancer: colorectal cancer, non-small cell lung cancer and breast cancer. In Europe, Avastin was approved early 2005 and in the USA in February 2004 for first-line treatment of patients with advanced colorectal cancer. Avastin was filed in April in the US for the most common form of lung cancer. The first filing for Avastin in Japan has been submitted last month for the treatment of advanced colorectal cancer.

About the E2100 study
This is the first phase III study to evaluate Avastin in combination with chemotherapy for first-line treatment of metastatic breast cancer. This randomised, controlled, multi-centre study enrolled 722 women with previously untreated metastatic breast cancer. The study 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). The patients were randomised to receive treatment with paclitaxel with or without Avastin. Avastin was given at a dose of 10mg/kg every two weeks until disease progression. The results showed that patients receiving Avastin plus paclitaxel had a median PFS of more than a year while patients receiving paclitaxel alone had a median PFS of approximately six months. Overall in the trial, patients treated with Avastin plus paclitaxel had a 52 percent reduction in the risk of disease progression or death, as expressed by a hazard ratio of 0.48 (1-0.48=0.52 or 52%), which is also identical to doubling PFS (1/0.48= ~2). Overall survival data for this trial are currently immature.

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.

About Avastin
Avastin is the first treatment that inhibits angiogenesis - the growth of a network of blood vessels that supply nutrients and oxygen to cancerous tissues. Avastin targets a naturally occurring protein called VEGF (Vascular Endothelial Growth Factor), a key mediator of angiogenesis, thus choking off the blood supply that is essential for the growth of the tumour and its spread throughout the body (metastasis).

Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of Avastin in various tumour types (including colorectal, breast, lung, pancreatic cancer, ovarian cancer, renal cell carcinoma and others) and different settings (advanced and adjuvant ie post-operation). The total development programme is expected to include over 25,000 patients worldwide.