Genentech announces Phase III study results for Avastin (bevacizumab) in combination with chemo in HER2-negative breast cancer

Genentech, Inc. today announced that a Phase III study (RIBBON 2) of Avastin (bevacizumab) in combination with chemotherapy increased the time women with metastatic HER2-negative breast cancer whose initial chemotherapy had stopped working lived without the disease worsening (progression-free survival or PFS), compared to chemotherapy alone.

The doctors treating the women in the study chose the type of chemotherapy used in combination with Avastin and the chemotherapies were assessed together in the primary endpoint analysis. Adverse events were consistent with those previously reported for Avastin, and no new Avastin safety signals were observed in the study. Data from the study will be submitted for presentation at a future medical meeting.

“Advanced breast cancer is aggressive and nearly all women will need additional treatment when initial chemotherapy stops working,” said Hal Barron, M.D., executive vice president, Global Development and chief medical officer. “We have learned for the first time that Avastin given in the second-line with standard chemotherapies helped women live longer without the disease worsening and look forward to discussing these new data with the FDA.”

Avastin, in combination with paclitaxel, was approved for first-line treatment of advanced HER2-negative breast cancer in February 2008 under the U.S. Food and Drug Administration's (FDA) accelerated approval program, which allows provisional approval of medicines for cancer or other life-threatening diseases. Avastin, in combination with paclitaxel, is indicated for the treatment of patients who have not received chemotherapy for advanced HER2-negative breast cancer. The effectiveness of Avastin in metastatic breast cancer is based on an improvement in PFS. Avastin is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Avastin in breast cancer.

A full review of data from the previously announced RIBBON 1 and AVADO studies is required for the accelerated approval of Avastin for the treatment of patients who have not received chemotherapy for advanced HER2-negative breast cancer (first-line treatment) to be converted into a full approval. Results from these trials will be submitted to the FDA later this year. Genentech is committed to understanding the potential role of Avastin in breast cancer and will submit data from the new study (RIBBON 2) of Avastin in the second-line to the FDA. Additionally, the data from two other ongoing randomized Phase III trials in the first-line setting will also be submitted to the FDA when available.

About RIBBON 2 (AVF3693g)

RIBBON 2 is an international, multicenter, randomized, double-blind, placebo-controlled clinical study that enrolled 684 patients with metastatic HER2-negative breast cancer who had previously received chemotherapy for their metastatic disease. The trial evaluated the addition of either Avastin or placebo to an investigator’s choice of chemotherapy. The following chemotherapy regimens were used in the study:

• Taxanes: paclitaxel, protein-bound paclitaxel or docetaxel
• Gemcitabine
• Capecitabine
• Vinorelbine

In the study, PFS was defined as the time from randomization to disease progression or death as assessed by the treating physicians in the study. Secondary endpoints included objective response rate, duration of response, one-year survival rate, overall survival, PFS assessment by chemotherapy type and safety.

About Avastin

Avastin is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin interferes with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. Avastin does not bind to receptors on normal or cancer cells. The tumor blood supply is thought to be critical to a tumor's ability to grow and spread in the body (metastasize).

Avastin was the first anti-angiogenesis therapy approved by the FDA and is approved for the treatment of five tumor types. Avastin is indicated for the first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy; for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel; for the treatment of metastatic renal cell carcinoma in combination with interferon alfa; for previously untreated, metastatic HER2-negative breast cancer in combination with paclitaxel; and for glioblastoma that has progressed following prior therapy.

The effectiveness of Avastin in metastatic breast cancer is based on an improvement in PFS. Avastin is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Avastin in breast cancer.

The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate as assessed by magnetic resonance imaging (MRI) and measured using World Health Organization radiographic criteria along with decreased or stable corticosteroid use. MRI does not necessarily distinguish between the tumor, swelling (edema) or tissue death (necrosis) caused by prior radiation therapy. Currently, no data are available from randomized controlled trials demonstrating an improvement in disease-related symptoms or increased survival with Avastin in glioblastoma.

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