Sunday, Jun 6, 2010
Chicago -- June 6, 2010 --Genentech, Inc., a wholly owned member of the Roche Group, (SIX: RO, ROG; OTCQX: RHHBY) today announced results from a Phase III study of Avastin® (bevacizumab) that showed women with previously untreated advanced ovarian cancer who received Avastin in combination with chemotherapy, followed by the continuation of Avastin alone, had a 39 percent improvement in the likelihood of living longer without the disease worsening (progression-free survival or PFS) compared to chemotherapy alone. An assessment of safety noted adverse events consistent with those observed in pivotal trials of Avastin. The study (known as GOG 0218), was conducted by a network of researchers led by the Gynecologic Oncology Group (GOG).
These results were featured in a press briefing today at the 46th Annual Meeting of the American Society of Clinical Oncology. Full results will be presented at the ASCO plenary session by Dr. Robert Burger, M.D., the GOG 0218 Study Chair and Director of the Women's Cancer Center at Fox Chase Cancer Center (Abstract LBA001, Sunday June 6, 1:45 p.m. CDT).
"Ovarian cancer is a difficult-to-treat disease with high morbidity and mortality, and there have been limited advances in treatment in the past decade," said Dr. Burger. "These results may represent an important step forward for women who need more options."
GOG 0218 demonstrated that women with advanced ovarian cancer who received front-line (first-line following surgery) Avastin in combination with chemotherapy (paclitaxel and carboplatin), and continued use of Avastin alone for a total duration of up to 15 months, had a median PFS of 14.1 months compared to 10.3 months in women who received chemotherapy alone (hazard ratio=0.72, p=<0.0001, a 28 percent reduction in the risk of cancer progression or death, which corresponds to a 39 percent improvement in the likelihood of living longer without the disease worsening). The study also investigated Avastin in combination with chemotherapy but without the continuation of Avastin alone. Women who received this shorter duration of Avastin did not have a statistically significant increase in PFS compared with chemotherapy alone.
"We are encouraged by these results as there have been few improvements in outcomes for women with this disease in the past decade. Avastin in combination with chemotherapy, followed by the continued use of Avastin, helped women with advanced ovarian cancer live longer without their disease worsening," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer. "We will discuss these data and next steps with U.S. and global regulatory authorities."
Adverse events (observed between cycle two and 30 days after last treatment) that occurred at a higher frequency in patients who received Avastin in combination with chemotherapy, followed by the continuation of Avastin alone, compared to patients who received chemotherapy alone, were neutropenia (low white blood cell count; Grade 4 or higher; 63.3 percent vs. 57.7 percent), pain (Grade 3 or higher; 13.7 percent vs. 9.2 percent) and hypertension (high blood pressure; Grade 3 or higher; 10.4 percent vs. 1.7 percent). Gastrointestinal (GI) events (Grade 2 or higher) including perforation (a hole in the stomach, small intestine, or large intestine), fistula (an abnormal passage from one part of the body to another), necrosis (bowel tissue dying) and leak occurred in 2.6 percent vs. 1.2 percent.
Additional efficacy analysis
The GOG 0218 study protocol allowed for different ways to determine if a patient's disease had progressed (worsened). Disease progression could be measured based exclusively on levels of a protein (CA-125) in the blood, or through the use of CA-125 levels and evidence of progression by a radiograph/scan. (CA-125 is measured by a blood test and is sometimes used to demonstrate a response to chemotherapy or to diagnose a recurrence or progression of ovarian cancer.)
An analysis of efficacy was conducted for regulatory purposes that only included disease progressions determined by radiographs/scans (excluding progressions based on CA-125 alone). In this analysis, women who continued Avastin, following Avastin in combination with chemotherapy, had a median PFS of 18.0 months compared to 12.0 months in women who received chemotherapy alone, increasing the likelihood of them living longer without the disease worsening by 54 percent (based on a hazard ratio=0.65, p=<0.0001, which corresponds to a 35 percent reduction in the risk of cancer progression or death).
About the GOG 0218 Study
GOG 0218 is an international, multi-center, randomized, double-blind, placebo-controlled Phase III study in 1,873 women with previously untreated advanced epithelial ovarian, primary peritoneal or fallopian tube carcinoma who already had surgery to remove as much of the tumor as possible. Patients were randomized to receive one of the following:
The primary endpoint of the study was PFS as assessed by trial investigators. Secondary and exploratory endpoints of the study included overall survival, PFS by independent review, safety, quality of life measures and analysis of patient tumor and blood samples.
About Ovarian Cancer
According to the American Cancer Society, ovarian cancer is the fifth leading cause of cancer death among American women. In 2009 an estimated 21,500 women were diagnosed with ovarian cancer and approximately 14,500 died from the disease in the United States. The disease causes more deaths than any other gynecologic cancer, and the American Cancer Society estimates that nearly 70 percent of women with advanced disease will die from it within five years.
Ovarian cancer is associated with high levels of vascular endothelial growth factor (VEGF), a protein associated with tumor growth and spread. Studies have shown a correlation between a high level of VEGF and a poorer prognosis in women with ovarian cancer. Currently, treatment options for women with this disease are limited to surgery and chemotherapy.
Avastin is a solution for intravenous infusion and is a biologic antibody designed to specifically bind to a protein called VEGF. VEGF 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.
Boxed WARNINGS and Additional Important Safety Information
People treated with Avastin may experience side effects. In clinical trials, some people treated with Avastin experienced serious and sometimes fatal side effects, including:
Gastrointestinal (GI) perforation: Treatment with Avastin can result in the development of a potentially 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 more people who received Avastin than in the comparison group (0.3 percent to 2.4 percent). In some cases, GI perforation resulted in fatality.
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. Surgery and wound healing problems occurred more often in people who received Avastin than in the comparison group. Avastin therapy should not be started for at least 28 days after surgery and until the surgical wound is fully healed. The length of time between stopping Avastin and having voluntary surgery without the risk of having surgery and wound healing problems following surgery has not been determined.
Severe bleeding: Treatment with Avastin can result in serious bleeding, including coughing up blood, bleeding in the stomach, vomiting of blood, bleeding in the brain, nosebleeds and vaginal bleeding. These events occurred up to five times more often in people who received Avastin. Across cancer types, 1.2 percent to 4.6 percent of people who received Avastin experienced severe to fatal bleeding. People who have recently coughed up blood (greater than or equal to a half teaspoon of red blood) or have serious bleeding should not receive Avastin.
In clinical trials for different cancer types, there were additional serious and sometimes fatal side effects that occurred in more people who received Avastin than in those in the comparison group. The formation of an abnormal passage from parts of the body to another part (non-GI fistula formation) was seen in 0.3 percent or less of people. Severe to life-threatening stroke or heart problems were seen in 2.4 percent of people. Too much protein in the urine, which led to kidney problems, was seen in less than 1 percent of people. Additional serious side effects that occurred in more people who received Avastin than those in the comparison group included severe to life-threatening high blood pressure, which was seen in 5 percent to 18 percent of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.1 percent of people. Infusion reactions with the first dose of Avastin were uncommon and occurred in less than 3 percent of people and severe reactions occurred in 0.2 percent of people.
Common side effects that occurred in more than 10 percent of people who received Avastin for different cancer types, and at least twice the rate of the comparison group, were nosebleeds, headache, high blood pressure, inflammation of the nose, too much protein in the urine, taste change, dry skin, rectal bleeding, tear production disorder, back pain and inflammation of the skin (exfoliative dermatitis). Across all trials, treatment with Avastin was permanently stopped in 8.4 percent to 21 percent of people because of side effects.
Avastin may impair fertility. Patients who are pregnant or thinking of becoming pregnant should talk with their doctor about the potential risk of loss of the pregnancy or the potential risk of Avastin to the fetus during and following Avastin therapy, and the need to continue an effective birth control method for at least six months following the last dose of Avastin.
For full Prescribing Information and Boxed WARNINGS on Avastin, please 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, California. For additional information about the company, please visit http://www.gene.com.
About The Gynecologic Oncology Group (GOG)
The Gynecologic Oncology Group is a non-profit organization of more than 300 member institutions with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of Gynecologic malignancies. The Group is committed to maintaining the highest standards in the clinical trial development, execution, analysis and distribution of results. Continuous evaluation of the GOG's processes is utilized in order to constantly improve the quality of patient care.
GOG receives support from the National Cancer Institute (NCI) of the National Institutes for Health (NIH).
1 One cycle = 3 weeks