FDA Approves Avastin for Second-Line Metastatic Colorectal Cancer

FDA Approves Avastin in Combination With Chemotherapy for Second-Line Metastatic Colorectal Cancer Patients

SOUTH SAN FRANCISCO, Calif., June 20, 2006 -- Genentech, Inc. announced today that the U.S. Food and Drug Administration (FDA) approved Avastin (bevacizumab) in combination with intravenous 5-fluorouracil (5-FU)-based chemotherapy for second-line metastatic colorectal cancer. Avastin is also approved as a first-line treatment of metastatic colorectal cancer (CRC) in combination with intravenous 5-FU-based chemotherapy.

"Avastin is the only biologic therapy with a demonstrated survival benefit in colorectal cancer, and this new indication offers CRC patients who have received a previous treatment regimen a new option to help fight their disease," said Hal Barron, M.D., senior vice president, Development and chief medical officer at Genentech. "Avastin used in combination with chemotherapy has become an important component of care for patients with metastatic colorectal cancer. We continue to study Avastin in both the adjuvant and metastatic settings, and Phase III trials in kidney, breast, pancreatic, non-small cell lung, prostate and ovarian cancers are ongoing in the hope that we may be able to help patients with other cancers as well."

The approval is based on results of a randomized, controlled, multicenter Phase III trial (E3200) of 829 patients with advanced or metastatic CRC who had received previous treatment with irinotecan and 5-FU as initial therapy for metastatic disease or as adjuvent therapy. The study showed that patients who received Avastin plus the 5-FU-based chemotherapy regimen known as FOLFOX4 (oxaliplatin/5-FU/leucovorin) had a 25 percent reduction in the risk of death (based on a hazard ratio of 0.75), the primary endpoint, which is equivalent to a 33 percent improvement in overall survival, compared to patients who received FOLFOX4 alone. Median survival for patients receiving Avastin plus FOLFOX4 was 13.0 months, compared to 10.8 months for those receiving FOLFOX4 alone.

"Colorectal cancer is the second leading cause of cancer death in the United States, so we are encouraged by new treatments and options that are leading to increased survival for patients," said Amy E. Kelly, Co-founder and Executive Director of the Colon Cancer Alliance. "We believe Avastin is an important advance that offers hope for prolonging survival for patients, including those who have already been through first-line treatment."

In the E3200 study, the most common Grade 3-5 (non-hematologic) and Grade 4/5 (hematologic) adverse events which occurred at a higher incidence (>/= 2 percent) in the Avastin plus FOLFOX4 arm, compared to the FOLFOX4 alone arm, were: diarrhea, nausea, vomiting, dehydration, ileus, sensory neuropathy, other neurologic events, fatigue, abdominal pain, headache, hypertension and hemorrhage.

The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG). Genentech provided Avastin for the trial under the Cooperative Research and Development Agreement (CRADA) with the NCI for the clinical development of Avastin, as well as financial support for data management.

About Avastin

Avastin is a therapeutic antibody designed to inhibit Vascular Endothelial Growth Factor (VEGF), a protein that plays an important role in tumor angiogenesis and maintenance of existing tumor vessels. By inhibiting VEGF, Avastin is designed to interfere with the blood supply to a tumor, a process that is thought to be critical to a tumor's growth and metastasis.

Avastin, in combination with intravenous 5-FU-based chemotherapy, is indicated for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum. The FDA first approved Avastin on February 26, 2004 as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. Approval was based on data from two trials. The pivotal trial was a large, placebo-controlled, randomized study that demonstrated a prolongation in the median survival of patients treated with Avastin plus the IFL (5-FU/leucovorin/CPT-11) chemotherapy regimen by approximately five months, compared to patients treated with the IFL chemotherapy regimen alone (20.3 months versus 15.6 months). The addition of Avastin to IFL improved overall survival by 52 percent (based on a hazard ratio of 0.66). In addition, this study demonstrated an improvement in progression-free survival of more than four months (10.6 months in the Avastin/IFL arm compared to 6.2 months in the IFL-alone arm).

Avastin Safety

Avastin has a well-established safety profile. In Genentech-sponsored studies, the most serious adverse events associated with Avastin were gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, 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, pancreatic, 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. In April 2006, Genentech submitted an sBLA for Avastin plus platinum-based chemotherapy for first-line treatment of advanced non-small cell lung cancer other than predominant squamous histology. In May 2006, Genentech submitted an sBLA for Avastin in combination with taxane chemotherapy for patients who have not previously received chemotherapy for their locally recurrent or metastatic breast cancer. For further information about Avastin clinical trials, please call 888-662-6728.

About VEGF and Tumor Angiogenesis

Genentech is a leader in research and product development in the area of angiogenesis, the process by which new blood vessels are formed. The link between angiogenesis and cancer growth has been discussed by many researchers for decades. It wasn't until 1989 that a key growth factor influencing the process, VEGF, was discovered by Napoleone Ferrara, M.D., a staff scientist at Genentech. Dr. Ferrara and his team at Genentech cloned VEGF, providing some of the first evidence that a specific angiogenic growth factor existed. This research was published in the journal Science in 1989. Dr. Ferrara then created a mouse antibody to this protein.

In 1993, in a study published in Nature, Dr. Ferrara and his team demonstrated that the antibody directed against VEGF could suppress angiogenesis and tumor growth in preclinical models, providing compelling evidence that VEGF can play a critical role in tumor growth. Clinical studies with a humanized version of the antibody, Avastin, began in 1997.

About Colorectal Cancer

According to the American Cancer Society (ACS), more than 150 patients die every day from colorectal cancer in the United States. Colorectal cancer is the second leading cause of cancer death in the United States and the third most frequently diagnosed cancer. The ACS estimates there will be 148,610 new cases of colorectal cancer diagnosed and 55,170 colorectal cancer deaths in 2006.

For more information on Avastin, please visit www.avastin.com.

Source: Genentech

Posted: June 2006


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