Monday, Aug 17, 2009
South San Francisco, Calif. -- August 17, 2009 --Genentech, Inc., a wholly-owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), 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:
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). For more information about angiogenesis, visit http://www.gene.com.
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.
BOXED WARNINGS and Additional Important Safety Information
Patients treated with Avastin may experience side effects. In clinical trials, some patients treated with Avastin experienced serious side effects, including:
Gastrointestinal (GI) perforation:
Treatment with Avastin can result in the development of a serious side effect called GI perforation, which is the development of a hole in the stomach, small intestine, or large intestine. In clinical trials, this side effect occurred in 0.3 to 2.4 percent of patients and in some cases resulted in fatality. Avastin therapy should be permanently stopped in people with GI perforation.
Surgery and wound healing problems:
Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases this event resulted in fatality. In a clinical trial, 15 percent of patients with metastatic colorectal cancer who had surgery while receiving Avastin treatment had serious and fatal complications compared to 4 percent of patients who did not receive Avastin. Avastin should not be initiated for at least 28 days following surgery and until the surgical wound is fully healed. Avastin therapy should be permanently stopped in patients with wound healing problems that require medical treatment. The appropriate waiting time between stopping treatment with Avastin and having surgery has not been determined.
Severe or fatal bleeding, including hemoptysis (coughing up of blood), GI bleeding, hematemesis (bloody vomit), central nervous system (CNS) hemorrhage (bleeding in the brain), epistaxis (nose bleeds), and vaginal bleeding occurred up to five-fold more frequently in patients receiving Avastin compared to patients receiving only chemotherapy. Across indications, Grade 3 or higher (severe or fatal) bleeding events have occurred in 1.2 to 4.6 percent of patients receiving Avastin. In patients with previously treated glioblastoma, intracranial hemorrhage (bleeding within the brain) occurred in 8 of 163 patients and two people had Grade 3 to 4 (severe) bleeding. In patients treated with Avastin and chemotherapy for lung cancer, serious and sometimes fatal pulmonary hemorrhage (bleeding in the lungs) occurred in four of 13 (31 percent) patients with squamous cell histology and two of 53 (4 percent) patients with non-squamous NSCLC, compared to none of 32 (0 percent) patients treated with chemotherapy. People with serious bleeding or recent hemoptysis (>/= to ½ tsp of red blood) should not receive Avastin. Discontinue Avastin if serious bleeding (ie, requiring medical care).
In clinical trials, additional serious side effects seen across different cancer types, in some cases resulting in fatality, included the following: formation of an abnormal passage from parts of the body to another part (non-GI fistula formation - less than 0.3 percent); stroke or heart problems (arterial thromboembolic events - 2.4 percent); high blood pressure (5 to 18 percent); nervous system and vision disturbances known as RPLS (reversible posterior leukoencephalopathy syndrome - less than 0.1 percent); severe infusion reactions (0.2 percent of people), too much protein in the urine and kidney damage (nephrotic syndrome - less than 1 percent). Infusion reactions with the first dose of Avastin were uncommon (less than 3 percent), and severe reactions occurred on 0.2% of patients.
The most common adverse reactions observed in Avastin patients at a rate of more than 10 percent and at least twice the control arm rate were nose bleeds, headache, high blood pressure, irritation of the nose (rhinitis), protein in the urine, taste alteration, dry skin, rectal bleeding, tear production disorder (lacrimation), back pain and inflammation of the skin (exfoliative dermatitis). Across all studies, Avastin was stopped in 8.4 to 20.3% of patients because of adverse reactions.
Grade 3-5 (nonhematologic) and 4-5 (hematologic) events in Study E2100 increased by 20.5% in the Avastin plus paclitaxel vs paclitaxel groups. The most common grade 3-5 (nonhematologic) and 4-5 (hematologic) events in Study E2100, which occurred at a higher absolute incidence (≥5%) in the Avastin plus paclitaxel vs. paclitaxel groups, were sensory neuropathy (24.2% vs. 17.5%), hypertension (16.0% vs. 1.4%), and fatigue (10.7% vs. 5.2%). The rate of CHF (defined as NCI-CTC grade 3?4) in the Avastin plus paclitaxel arm was 2.2% vs. 0.3% in the control arm. Among patients receiving anthracyclines, the rate of CHF was 3.8% for Avastin-treated patients and 0.6% for patients receiving paclitaxel alone. Only NCI-CTC grade 3-5 (nonhematologic) and grade 4-5 (hematologic) adverse events were reported. Therefore, grade 1-2 adverse events were not collected in Study E2100, and common adverse events of Avastin in combination with paclitaxel for metastatic breast cancer are not known. Fatal adverse reactions occurred in 1.7% (6/363) of patients who received Avastin plus paclitaxel in Study E2100. Causes of death were GI perforation (2), myocardial infarction (2), and diarrhea/abdominal pain/weakness/hypotension (2). Avastin may cause problems getting pregnant. People who are pregnant or thinking of becoming pregnant should talk with their doctor about the potential risks of loss of pregnancy or the potential risk of Avastin to the fetus. Nursing mothers should not breast-feed while receiving Avastin or for a short period of time after treatment is finished. Avastin may impair fertility.
For full Prescribing Information and Boxed WARNINGS on Avastin visit http://www.avastin.com.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a wholly-owned member of the Roche Group, has headquarters in South San Francisco, Calif. For additional information about the company, please visit http://www.gene.com.