Phase III C-08 Study of Avastin in Early-Stage Colon Cancer Did Not Meet Primary Endpoint

Genentech and Roche Remain Committed to Avastin Adjuvant Colon, Breast and Lung Cancer Programs

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Apr 22, 2009 - Genentech, Inc. announced today that a Phase III study of Avastin® (bevacizumab) plus chemotherapy following surgery in patients with early-stage (adjuvant) colon cancer (NSABP C-08) did not meet its primary endpoint of reducing the risk of cancer returning (improvement in disease-free survival). Results are from a planned final analysis of the study. This is the first trial of Avastin in early-stage cancer and results do not affect approved indications in advanced (metastatic) disease.

Safety findings were consistent with those presented from this study at the 2008 American Society of Clinical Oncology (ASCO) annual meeting (Allegra et al.). Data from the trial have been submitted for presentation at the upcoming ASCO annual meeting, May 29 – June 2, 2009.

“While we are disappointed the C-08 study did not meet its primary endpoint, our initial review of the data leads us to continue to believe Avastin may be active in patients with early-stage colon cancer and look forward to NSABP's presentation at ASCO,” said Hal Barron, M.D., senior vice president, Development and chief medical officer, Genentech. “We remain fully committed to the ongoing Avastin adjuvant programs in early-stage colon, breast and lung cancers.”

“In order to provide patients with the full potential benefit of Avastin in early-stage cancer, we believe the findings of the C-08 trial should be considered for the ongoing adjuvant trial programs,” said William M. Burns, CEO of Roche's Pharmaceutical Division. “The current studies and indications in advanced disease are not affected.”

The C-08 study was conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and sponsored by the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement between Genentech and NCI.

About Adjuvant Cancer Therapy

Surgical removal of a tumor is typically the standard treatment for colon cancer that has not spread (metastasized) to other parts of the body. Often surgery is followed by an additional treatment (adjuvant therapy) to eliminate stray cancer cells that may have spread through the bloodstream before the tumor was removed. These cancer cells cannot be detected and have the potential to establish and grow into new tumors. The goal of adjuvant therapy given after the primary treatment for early-stage cancer is to increase the chance for a cure. Advanced cancers that have extensively spread throughout body are often incurable.

About the Study

NSABP C-08 is a randomized multi-center Phase III study designed to evaluate the effect of FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) chemotherapy with or without Avastin on disease-free survival in patients with resected Stage II or III adenocarcinoma of the colon. The trial was conducted primarily in the United States. Patients enrolled in the two-arm study were randomized after surgery to receive either FOLFOX chemotherapy alone for six months or FOLFOX in combination with Avastin (intravenous every two weeks) for six months, followed by an additional six months of Avastin monotherapy. The secondary endpoint of the study was overall survival.

About the Avastin Development Program

Results are expected in 2010 from a separate Roche-sponsored international Phase III study (AVANT) assessing Avastin in combination with chemotherapy for early-stage colon cancer. The three-arm trial is evaluating Avastin in combination with the chemotherapy regimens XELOX (capecitabine and oxaliplatin) or FOLFOX chemotherapy versus FOLFOX alone.

In addition to early-stage colon cancer, Avastin is being studied as an adjuvant treatment in other early-stage diseases: HER2-negative breast cancer, HER2-positive breast cancer and non-squamous, non-small cell lung cancer. Approximately 26,000 people are expected to participate in Avastin adjuvant studies.

The Avastin development program represents one of the most comprehensive undertakings in cancer research since chemotherapy and includes more than 450 clinical trials worldwide in approximately 30 different tumor types.

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. 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 is indicated for the first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy and for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC in combination with carboplatin and paclitaxel.

About Avastin in Metastatic Colorectal Cancer

Avastin in combination with IV 5-FU-based chemotherapy was proven to extend overall survival by 52 percent compared to chemotherapy alone in people with advanced colorectal cancer. This is one of the largest improvements in survival ever reported in a randomized Phase III advanced colorectal cancer study (hazard ratio 0.66). In a Phase III study in second-line advanced colon cancer, Avastin in combination with FOLFOX4 chemotherapy improved overall survival by 33 percent compared to chemotherapy alone (hazard ratio 0.75).

Avastin Safety

The most serious side effects associated with Avastin, in some cases resulting in death, across all trials were gastrointestinal (GI) perforation (the development of a hole in the stomach, small intestine, or large intestine), slow wound healing, severe bleeding, and blood clots. Additional serious side effects are formation of an abnormal passage from parts of the body to another part, severe high blood pressure, nervous system and vision disturbances, reduced white blood cell counts, kidney problems, and congestive heart failure. Treatment with Avastin can also result in slow wound healing and in some cases can cause the wound to reopen.

The most common serious adverse events across different cancer types were high blood pressure, blood clots, stroke, reduced white blood cell counts, infection, bleeding, weakness, abdominal pain, pain, headache, tiredness, a brief loss of consciousness, diarrhea, constipation, blockage of the bowel, nausea, vomiting, dehydration, numbness and tingling in fingers and toes, and too much protein in the urine. Patients receiving Avastin should have their blood pressure monitored every 2 to 3 weeks.

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.

Please visit http://www.gene.com for the Avastin full prescribing information, including Boxed WARNINGS and additional important safety information.

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.
Megan Pace, 650-467-7334 (Media)
Kathee Littrell, 650-225-1034 (Investors)
Kristin Reed, 650-467-9831 (Advocacy)

Posted: April 2009

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