Roche has submitted a Marketing Authorisation application to the European Medicines Agency (EMEA) for the use of its innovative new cancer drug Avastin in previously untreated advanced (metastatic) breast cancer.

The filing is based on impressive phase III trial data which show that the addition of Avastin to standard chemotherapy as a primary treatment for advanced breast cancer doubled the time women lived without their disease advancing, compared to chemotherapy alone. This is remarkable and the first phase III study involving an anti-angiogenic agent to report positive outcome for patients with advanced breast cancer.

"Breast cancer is a devastating disease and is the leading cause of cancer death in women in Europe, affecting more than one in ten women. Avastin has shown excellent progression-free survival data in treating the disease," says Eduard Holdener, Head of Roche Pharmaceuticals Development. "The filing is an important milestone, demonstrating that anti-angiogenic therapy is changing the way that cancer is treated. It is a further step forward for Avastin to become part of the treatment armamentarium for a whole range of tumour types."

After colorectal and lung cancer, breast cancer is the third type of cancer in which the anti-angiogenic agent Avastin has demonstrated significant survival benefit. Roche plans to file Avastin in Europe later this year in advanced NSCLC, the most common form of lung cancer, as well as to broaden the current label in metastatic colorectal cancer.

In Europe, Avastin was approved in early 2005 and in the US in February 2004 for first-line treatment of patients with advanced colorectal cancer. It received another approval in the US in June 2006 as a second-line treatment for patients with advanced colorectal cancer. In addition, Avastin was filed in April this year in the US for NSCLC. The first filing for Avastin in Japan occurred the same month for the treatment of advanced colorectal cancer. Most recently in May 2006 Avastin was filed in the US for the treatment of women with advanced breast cancer.

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 progression-free survival (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 per cent 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 per cent), 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.

Overall, Avastin was safe and well tolerated in patients with locally recurrent or metastatic breast cancer at the recommended dose of 10 mg/kg every two weeks.

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, prostate and others) and different settings (advanced and adjuvant ie post-operation). The total development programme is expected to include over 40,000 patients worldwide.