SOUTH SAN FRANCISCO, Calif., Dec. 13 /PRNewswire-FirstCall/ -- Genentech, Inc. announced today the publication of data from a pivotal Phase III clinical trial in the New England Journal of Medicine showing that Avastin(R) (bevacizumab) in combination with paclitaxel and carboplatin chemotherapy significantly improved overall survival in patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non- small cell lung cancer (NSCLC), the most common type of lung cancer. Based on this study (E4599), the U.S. Food and Drug Administration (FDA) recently approved Avastin as a first-line treatment in combination with paclitaxel and carboplatin chemotherapy for patients with this advanced form of lung cancer.
This year in the United States, the American Cancer Society estimates that lung cancer will kill more people than breast, prostate, colon, liver and kidney cancers combined, making it the leading cause of cancer death among Americans. Because most lung cancers are diagnosed during a late stage of the disease, only approximately 15 percent of patients live five years.
"This is the first large, randomized clinical study in which a targeted therapy, combined with chemotherapy, extended survival beyond one year in patients with advanced lung cancer," said Alan B. Sandler, M.D., director of Medical Thoracic Oncology at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., and study chair for the E4599 trial. "The results of this study have changed the treatment standard of care for this devastating disease -- an important step forward for patients with advanced lung cancer."
According to the published study, patients receiving Avastin added to a standard chemotherapy regimen of paclitaxel and carboplatin had an approximate 27 percent improvement in overall survival, the primary endpoint of the trial, compared to patients who received chemotherapy alone (based on a hazard ratio of 0.79, which can also be described as a 21 percent reduction in the risk of death). Median survival of patients treated with Avastin plus chemotherapy was 12.3 months versus 10.3 months for patients treated with chemotherapy alone. One-year survival was 51 percent for patients receiving Avastin plus chemotherapy versus 44 percent for patients who received chemotherapy alone. Two-year survival was 23 percent versus 15 percent.
The published study also showed that patients treated with Avastin plus chemotherapy experienced a 52 percent improvement in progression-free survival (based on a hazard ratio of 0.66). Median progression-free survival was 6.2 months for patients treated with Avastin plus chemotherapy, compared to 4.5 months for patients who received chemotherapy alone. The response rate as determined by study investigators was 35 percent (133/381) in the group receiving Avastin plus chemotherapy, compared to 15 percent (59/392) in the group receiving chemotherapy alone. Progression-free survival and response rate were based on investigator assessments and were not independently verified.
"The publication of this study is the result of many years of clinical research on the role of Avastin, and inhibiting blood vessel growth by specifically targeting VEGF, in the treatment of various types of cancer," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer. "We continue to explore the optimal use of Avastin for patients with advanced lung cancer, as well as to evaluate its potential benefits for patients with other difficult-to-treat cancers."
About the Pivotal Study (E4599)
This randomized, open-label, multi-center U.S. trial enrolled 878 patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. Patients with tumors classified as squamous (as the predominant cell type in mixed histology), central nervous system metastases, clinically significant hemoptysis (coughing up 1/2 teaspoon or more of red blood), inadequate organ function or performance status (ECOG performance status, >1), or unstable angina and those receiving therapeutic anticoagulation were excluded. Patients were randomized to receive treatment with paclitaxel (200 mg/m2) and carboplatin (AUC=6 mg/mL/minute) chemotherapy with or without Avastin (15 mg/kg). Chemotherapy was administered with Avastin on day one every 21 days for six cycles. After completion of chemotherapy, Avastin was administered on day one every 21 days until disease progression or development of intolerable toxicity. After the baseline evaluation, tumor status was assessed every six weeks for 24 weeks, every nine weeks for the remainder of therapy and every 12 weeks post-therapy.
The E4599 trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), under a Cooperative Research and Development Agreement between NCI and Genentech. The trial was conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG).
E4599 Safety Analysis
According to the study published in the New England Journal of Medicine, the rates of the following severe (Grade 3-5 for non-hematologic and Grade 4-5 for hematologic) adverse events were significantly higher in patients receiving Avastin plus chemotherapy compared to patients receiving chemotherapy alone: hypertension (high blood pressure), proteinuria, bleeding, neutropenia (low white blood cell count), febrile neutropenia, thrombocytopenia, hyponatremia (low blood sodium), rash and headache. Neutropenia occurred in 26 percent (109/427) of patients treated with Avastin plus chemotherapy and 17 percent (74/440) of patients who received chemotherapy alone.
In this published study, the rate of hemoptysis requiring medical intervention for the Avastin plus chemotherapy arm was 1.9 percent (8/427), compared to 0.2 percent (1/440) for the paclitaxel and carboplatin-alone arm. There were 15 deaths related to the adverse treatment effects in patients treated with Avastin plus chemotherapy, of which 5 were due to pulmonary hemorrhage, 5 were due to complications of febrile neutropenia, and the remainder were due to other sites of hemorrhage and a probable pulmonary embolism. For patients treated with chemotherapy alone, two deaths related to the adverse effects of treatment occurred, of which one was from gastrointestinal hemorrhage and one from febrile neutropenia.
In previous clinical trial experience with Avastin in combination with paclitaxel and carboplatin in NSCLC, patients with a specific type of NSCLC called squamous cell carcinoma had a higher risk of experiencing life- threatening or fatal pulmonary bleeding. Squamous cells are particular kinds of cells that form in the lining of the air ducts in the lung. Because of the risk of bleeding attributed to this population, patients with NSCLC classified as predominantly squamous histology were not included in this trial.
About Avastin
Avastin is a therapeutic antibody designed to specifically inhibit vascular endothelial growth factor (VEGF), a protein that plays an important role in tumor angiogenesis and the maintenance of existing tumor vessels. Avastin is designed to interfere with the blood supply to a tumor, which is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). For more information on angiogenesis, visit http://www.gene.com/ . For full prescribing information and boxed warnings on Avastin, visit http://www.avastin.com/ .
Avastin Safety
The most serious adverse events associated with Avastin across all trials were gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome (RPLS), neutropenia and infection, nephrotic syndrome and congestive heart failure. The most common adverse events in patients receiving Avastin were asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis and proteinuria.
About the Avastin Development Program
Based on data showing that VEGF may play a broad role in a range of cancers, Genentech is pursuing a broad development program for Avastin that currently includes 130 clinical trials across 25 different types of cancer. Avastin is being evaluated in Phase III clinical trials for its potential use in adjuvant and metastatic colorectal, renal cell (kidney), breast, non-small cell lung, prostate and ovarian cancers. Avastin is also being evaluated in earlier-stage trials as a potential therapy in a variety of solid tumor cancers and hematologic malignancies. For further information about Avastin clinical trials, please call 888-662-6728.
Genentech's Commitment to Patient Access
Genentech is committed to assisting eligible patients in accessing our therapies for approved indications, regardless of their ability to pay. Although Genentech's products are covered by most government and private insurance, Genentech established the Genentech(R) Access to Care Foundation (GATCF) in 1990 for its marketed products, and donates free product to eligible uninsured patients in the United States, except for Pulmozyme(R) (dornase alfa, recombinant), which is covered by the Genentech Endowment for Cystic Fibrosis. Since 1985, Genentech has donated approximately $890 million of free medicine to uninsured patients, with approximately $200 million of medicine donated to 18,000 patients in 2005 alone as part of the Access to Care Foundation and the Genentech Endowment for Cystic Fibrosis.
In January 2007, Genentech plans to launch a first-of-its-kind program to cap the overall expense of Avastin at $55,000 per year per eligible patient for any FDA-approved indication. The program will be available for eligible patients regardless of whether they are insured. In addition, in October 2006 the company doubled its contribution to independent charities that provide co- pay assistance to a total of $50 million.
About Genentech
Founded 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes multiple biotechnology products directly in the United States and licenses several additional products to other companies. The company has headquarters in South San Francisco, Calif., and is listed on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit http://www.gene.com/ .
For the full prescribing information for Avastin please visit http://www.gene.com/ .
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