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FDA Approves Avastin for Brain Cancer (Glioblastoma)

FDA Grants Accelerated Approval of Avastin for Brain Cancer (Glioblastoma) That Has Progressed Following Prior Therapy

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--May 5, 2009 - Genentech, Inc. announced today that the U.S. Food and Drug Administration (FDA) granted accelerated approval of Avastin (bevacizumab) for people with glioblastoma with progressive disease following prior therapy. The effectiveness of Avastin in this aggressive form of brain cancer is based on an improvement in objective response rate. Currently, no data are available from randomized controlled trials demonstrating an improvement in disease-related symptoms or increased survival with Avastin in glioblastoma.

The new indication for Avastin was granted under the FDA's accelerated approval program that allows provisional approval of medicines for cancer or other life-threatening diseases.

"People with this type of brain cancer have had no new treatments in more than a decade," said Timothy Cloughesy, M.D., director, Neuro-Oncology Program of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. "After so many years with little progress in this field, Avastin was associated with a durable tumor response and doctors now have a new medicine to offer patients."

"Today's approval would not have been possible without the dedication of physicians, patient advocates, the FDA and most importantly the people who participated in the clinical trials and their families who had the courage to support them," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. "A global Phase III trial in patients with newly diagnosed glioblastoma will soon begin enrollment to further evaluate Avastin in this setting."

Glioblastoma affects approximately 10,000 people per year in the United States and glioblastoma tumors nearly always return following initial treatment.

Avastin Efficacy in Glioblastoma

Study AVF3708g

The accelerated approval is based on independently reviewed data from an open-label, multicenter, non-comparative Phase II study that included 167 patients with glioblastoma that had progressed following initial treatment with temozolomide and radiation. Patients were randomized into two arms: Avastin alone or Avastin in combination with irinotecan. A primary endpoint of the study was objective response rate. Response was 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.

According to an FDA analysis of the study, tumor responses were observed in 26 percent (95% confidence interval: 17.0%, 36.1%) of the 85 patients treated with Avastin alone, and the median duration of response in these patients was 4.2 months (95% confidence interval: 3.0 months, 5.7 months).

The median age of the patients treated with Avastin alone was 54 years. Additionally, 32 percent were female, 81 percent were in first relapse, 45 percent had a Karnofsky performance status (KPS) of 90 to 100 and 55 percent had a KPS of 70 to 80. Patients with active brain hemorrhage were excluded from the study.

Study NCI 06-C-0064E

The efficacy of Avastin in glioblastoma that has progressed following prior therapy is supported by another study that used the same response assessment criteria as AVF3708g. In this single-arm study, 56 patients were treated with Avastin alone. Responses were observed in 20 percent of patients (95% confidence interval: 10.9%, 31.3%), and the median duration of response was 3.9 months (95% confidence interval: 2.4 months, 17.4 months).

Avastin Safety in Glioblastoma

In study AVF3708g, safety in patients with glioblastoma that had progressed following prior therapy was consistent with Avastin experience in other tumor types.

Safety in Patients Treated with Avastin Alone in AVF3708g

Avastin was discontinued due to adverse events in 5 percent of patients. The most frequently reported adverse events were infection (55 percent), fatigue (45 percent), headache (37 percent), high blood pressure (30 percent), diarrhea (21 percent) and nose bleeds (19 percent). Grade 3 or higher adverse events were infection (10 percent), high blood pressure (8 percent), fatigue (4 percent), headache (4 percent) and diarrhea (1 percent). There were two deaths possibly associated with adverse events including one retroperitoneal hemorrhage and one neutropenic infection.

Safety in All Patients in AVF3708g (Avastin Alone and Avastin Plus Irinotecan)

Avastin-related adverse events (Grades 1 to 4) across both arms of the study were bleeding/hemorrhage (40 percent), high blood pressure (32 percent), nose bleeds (26 percent), blood clots in the veins (8 percent), blood clots in the arteries (6 percent), wound-healing complications (6 percent), bleeding in the brain (5 percent), protein in the urine (4 percent), gastrointestinal (GI) perforation (2 percent), nervous system and vision disturbances known as reversible posterior leukoencephalopathy syndrome or RPLS (1 percent). Grade 3 to 5 adverse events across both arms of the study were blood clots in the veins (7 percent), high blood pressure (5 percent), blood clots in the arteries (3 percent), wound-healing complications (3 percent), GI perforation (2 percent), bleeding/hemorrhage (2 percent), bleeding in the brain (1 percent) and protein in the urine (1 percent).

About Avastin

Avastin is a biologic antibody designed to specifically inhibit the vascular endothelial growth factor (VEGF) protein that plays an important role in the development and maintenance of blood vessels, a process known as angiogenesis. Glioblastomas express high levels of VEGF and develop an extensive network of tumor blood vessels. VEGF is a potent activator of angiogenesis throughout the lifecycle of a tumor and 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 now approved for the treatment of four tumor types. In addition to glioblastoma that has progressed following prior therapy, Avastin is also indicated for the first- and second-line treatment of metastatic colorectal cancer (mCRC) 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; and for previously untreated, metastatic or locally recurrent HER2-negative breast cancer in combination with paclitaxel. The effectiveness of Avastin in metastatic breast cancer is based on an improvement in progression-free survival. 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.

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. 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 bleeding:

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 has occurred up to five-fold more frequently in patients receiving Avastin. 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 eight of 163 patients and two people had Grade 3 to 4 (severe) bleeding. Some people receiving Avastin with chemotherapy for lung cancer experienced hemoptysis. In some cases, this event resulted in fatality. People with serious bleeding or recent hemoptysis should not receive Avastin.

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 – 2.6 percent), high blood pressure (5 to 18 percent), nervous system and vision disturbances known as reversible posterior leukoencephalopathy syndrome or RPLS (less than 0.1 percent), severe infusion reactions (0.2 percent), and too much protein in the urine (that may be a sign of kidney problems) was increased.

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), and inflammation of the skin (exfoliative dermatitis).

Avastin may cause problems getting pregnant. Women 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.

For full Prescribing Information and Boxed WARNINGS on Avastin visit http://www.avastin.com.

About Genentech Access Solutions

Genentech is committed to people having access to our medicines. Genentech Access Solutions is a team of 350 Genentech employees who help those who need Genentech medicines. This team works with patients and doctors to resolve reimbursement and insurance issues and provides assistance to eligible patients in the United States who do not have insurance coverage or who cannot afford their out-of-pocket co-pay costs.

Since its first medicine was approved in 1985, Genentech has donated approximately $1.3 billion in free Genentech medicine to the uninsured through the Genentech Access to Care Foundation (GATCF) and other product donation programs. The household income limit to receive free medicine through GATCF is $100,000 per year. Since 2005, Genentech has also donated approximately $250 million to various independent, non-profit organizations that provide financial assistance to those who cannot access needed medical treatment due to co-pay costs.

About Genentech

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, California. For additional information about the company, please visit http://www.gene.com.

Contact: Genentech, Inc.

Media:

Charlotte Arnold, 650-467-6800

or

Investor:

Kathee Littrell, 650-225-1034

Karl Mahler, 011 41 61 687 85 03

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Advocacy:

Kristin Reed, 650-467-9831

***

Posted: May 2009

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