Monday, Feb 2, 2009
South San Francisco, Calif. -- February 2, 2009 --Genentech, Inc. (NYSE: DNA) today announced that a Phase III study (ATLAS) of Tarceva® (erlotinib) in combination with Avastin® (bevacizumab) as maintenance therapy following initial treatment with Avastin plus chemotherapy in advanced non-small cell lung cancer (NSCLC) met its primary endpoint. The study was stopped early on the recommendation of an independent data safety monitoring board after a pre-planned interim analysis showed that combining Tarceva and Avastin significantly extended the time patients lived without their disease advancing, as defined by progression-free survival (PFS), compared to Avastin plus placebo. A preliminary safety analysis showed adverse events were consistent with previous Avastin or Tarceva studies, as well as trials evaluating the two medicines together, and no new safety signals were observed. Data will be submitted for presentation at a future medical meeting.
"This is the second study to show that people with lung cancer who took the daily pill Tarceva following initial treatment lived longer without their cancer getting worse. We plan to discuss these data with the FDA to determine next steps," said Hal Barron, M.D., Genentech's senior vice president, Development and chief medical officer. "Tumors use different pathways to grow and these results showed that combining medicines targeting two of these pathways instead of one delayed disease progression."
An earlier study, SATURN, showed Tarceva delayed disease progression when given as a single agent immediately following treatment with chemotherapy, compared to placebo. In ATLAS, patients were initially treated with Avastin plus chemotherapy followed by the addition of Tarceva to Avastin in the maintenance phase.
Avastin is currently approved as first-line treatment in combination with carboplatin and paclitaxel chemotherapy for patients with locally advanced, non-squamous NSCLC and Tarceva is currently approved as a treatment for patients with advanced NSCLC who have progressed following treatment with at least one prior chemotherapy regimen. Both therapies have been shown to improve overall survival in these indications.
About ATLAS (AVF3671g)
ATLAS is a global, multicenter, randomized, double-blind, placebo-controlled study that enrolled 1,157 patients with locally advanced, recurrent or metastatic NSCLC. In order to evaluate patients who are often excluded from Avastin-based clinical trials, patients with treated brain metastases, tumors of squamous cell histology that were not centrally located in the lung, and those taking blood-thinning medications were eligible for this trial. Patients were initially treated with four cycles of Avastin in combination with the investigators' choice of platinum-based chemotherapy regimens (carboplatin/gemcitabine, carboplatin/paclitaxel, carboplatin/docetaxel, cisplatin/vinorelbine, cisplatin/docetaxel or cisplatin/gemcitabine). If their cancer did not progress and they did not experience significant toxicity, patients were then randomized (n=768) to receive maintenance therapy with Avastin plus Tarceva or Avastin plus placebo until disease progression.
The study's primary endpoint of PFS, as determined by investigators, was defined as the length of time from randomization to disease progression or death from any cause. PFS assessment began from the start of the maintenance phase of the study after initial treatment with four cycles of Avastin and chemotherapy. Secondary endpoints included overall survival, incidence of all adverse events and selected Grade 3 or greater adverse events and incidence of treatment discontinuation for reasons other than disease progression.
About Lung Cancer
According to the American Cancer Society (ACS), lung cancer is the single largest cause of cancer death among men and women in the U.S. and nearly 162,000 Americans died from the disease in 2008. Most people with lung cancer are diagnosed with advanced stage disease that cannot be surgically removed or has spread to other parts of the body. The majority of people with advanced lung cancer survive less than one year. NSCLC is the most common type of lung cancer.
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.
The most serious side effects associated with Avastin across all trials were gastrointestinal (GI) perforation, slow wound healing, severe bleeding, formation of an abnormal passage from parts of the body to another part, blood clots, severe high blood pressure, nervous system and vision disturbances, reduced white blood cell counts, kidney malfunction and congestive heart failure. The most common serious adverse events that may have occurred for Avastin for first- and second-line metastatic colorectal cancer and first-line non-small cell lung cancer included reduced white blood cell counts, tiredness, high blood pressure, infection, severe bleeding, weakness, abdominal pain, pain, blood clots, a brief loss of consciousness, diarrhea, constipation, nausea, vomiting, dehydration, blockage of the bowel, numbness and tingling in fingers and toes, nervous system disturbances and headache. For full Prescribing Information and Boxed Warnings for Avastin, visit http://www.avastin.com.
Tarceva is a once-a-day pill that targets the epidermal growth factor receptor (EGFR) pathway. Tarceva is designed to inhibit the tyrosine kinase activity of the EGFR signaling pathway inside the cell, one of the critical growth factors in NSCLC and pancreatic cancers. Tarceva is indicated as a monotherapy for patients with locally advanced or metastatic NSCLC whose disease has progressed after one or more courses of chemotherapy. Results from two multicenter, placebo-controlled, randomized Phase III trials conducted in first-line patients with locally advanced or metastatic NSCLC showed no clinical benefit with the concurrent administration of Tarceva with platinum-based chemotherapy (carboplatin and paclitaxel or gemcitabine and cisplatin) and its use is not recommended in that setting.
In pancreatic cancer, Tarceva is indicated in combination with gemcitabine for the first-line treatment of patients with locally advanced pancreatic cancer, pancreatic cancer that cannot be surgically removed or pancreatic cancer that has spread to distant body organs.
There have been infrequent reports of serious Interstitial Lung Disease (ILD)-like events, including fatalities, in patients receiving Tarceva for treatment of NSCLC, pancreatic cancer or other advanced solid tumors. Cases of hepatic failure, hepatorenal syndrome, acute renal failure (all including fatalities), and renal insufficiency have been reported during use of Tarceva. When receiving Tarceva therapy, women should be advised against becoming pregnant or breastfeeding. Tarceva is pregnancy category D. The most common adverse reactions in patients with NSCLC receiving Tarceva monotherapy were rash and diarrhea. The most common adverse reactions in patients with pancreatic cancer receiving Tarceva plus gemcitabine were fatigue, rash, nausea, anorexia and diarrhea. For full Prescribing Information for Tarceva, visit http://www.tarceva.com.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines for patients with significant unmet medical needs. The company has headquarters in South San Francisco, California 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.