The US Food and Drug Administration approved Genentech's Avastin for breast cancer, despite an FDA advisory panel narrowly recommending against the new use of the drug. The agency rarely goes against the recommendations of its outside advisory panels.

The Federal regulators had swept aside the objections raised by its advisory panel by approving Avastin (bevacizumab), in combination with paclitaxel chemotherapy, for the first-line treatment of patients with locally recurrent or metastatic breast cancer. Avastin is already approved as a treatment for lung and colon cancer and had $2.3 billion in sales last year.

The approval is based on a phase III study (E2100) which showed that for patients with metastatic breast cancer the addition of Avastin to paclitaxel compared to paclitaxel alone doubled the chance of being alive without the disease advancing ("progression-free survival"). In Europe Avastin received full approval for the treatment of metastatic breast cancer in March 2007.

Avastin was approved in advanced breast cancer under the FDA's accelerated approval programme, which allows the FDA to approve products for cancer or other life-threatening diseases based on initial positive clinical data. Genentech has shared with the FDA a summary of the results from a second positive phase III trial (AVADO = Avastin plus docetaxel chemotherapy vs docetaxel alone), and is expecting results from a third phase III trial (RIBBON-1) in first-line metastatic breast cancer in late 2008. A full review of both the AVADO and RIBBON-1 data by the FDA will be required for the accelerated approval to be converted into a full approval. As a part of Genentech's commitment to fully evaluate Avastin in breast cancer, they will also submit data to the FDA from three additional randomised trials that are either ongoing or planned.

"This is excellent news representing a significant advancement in breast cancer therapy." said Dr David Miles, medical oncologist, Mount Vernon Hospital, UK. "The decision confirms the importance of progression-free survival as a clinically meaningful benefit to patients. Avastin effectively doubles the time patients live without their disease advancing which is highly significant for our patients and their families."

Globally, breast cancer is the second most common form of cancer and the second leading cancer killer of women with an estimated annual death toll in excess of 400,000.1.

"Today's decision represents a major milestone for patients and oncologists in the US" said William M Burns, CEO, Roche Pharmaceuticals. "The FDA has recognized that Avastin is a breakthrough drug which is now approved in Europe and the US for the three cancers with the highest death toll breast, lung and colorectal cancer".

Avastin is the first anti-angiogenic agent which has been shown to consistently deliver improved overall and/or progression-free survival benefit for colorectal, lung, breast and, renal cell cancer patients.

The E2100 trial was sponsored by the National Cancer Institute under a Cooperative Research and Development Agreement and was conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG). E2100 was a multicentre, randomised and controlled clinical trial that enrolled 772 patients with previously untreated, locally recurrent or metastatic breast cancer. Patients were randomised to receive weekly treatment with paclitaxel every three out of four weeks, with or without Avastin.
Based on an independent, blinded review of patient scans, patients treated with Avastin plus paclitaxel experienced a 52 per cent reduction in the risk of disease progression or death compared to those treated with paclitaxel alone. In the Avastin arm, median PFS was 11.3 months versus 5.8 months in the paclitaxel alone arm. Based on the investigator assessment, patients treated with Avastin plus paclitaxel experienced a 58 per cent reduction in the risk of disease progression or death compared to those treated with paclitaxel alone. The data showed a similar magnitude of benefit relative to the initial results presented by ECOG at the American Society of Clinical Oncology annual meeting in 2005 and published by ECOG in the New England Journal of Medicine in 2007. The secondary endpoint of overall survival was longer in the Avastin-containing arm, as indicated by the hazard ratio of 0.87 but this improvement did not reach statistical significance. A one year exploratory analysis of overall survival was significantly improved with the addition of Avastin.

Safety findings were generally consistent with previous trials of Avastin plus chemotherapy and no new safety signals related to Avastin were observed. Grade 3-4 adverse events that occurred more often in the Avastin arm included neuropathy (due to longer time on paclitaxel treatment), hypertension, arterial thromboembolic events (ATEs) and proteinuria. The incidence of hypertension, ATEs and gastrointestinal (GI) perforation in E2100 was consistent with that described in previous Avastin studies.