Saturday, May 30, 2009

Phase III Study Showed Patients Lived Longer Without Advanced Lung Cancer Progressing When Tarceva Was Added to Avastin as First-Line Maintenance Therapy

Orlando, Fla. -- May 30, 2009 --

Genentech, Inc. today announced that a Phase III study (ATLAS) showed patients with advanced non-small cell lung cancer (NSCLC) who received Tarceva® (erlotinib) in combination with Avastin® (bevacizumab) as first-line maintenance treatment had a 39 percent improvement in the time they lived without the disease advancing (progression-free survival or PFS), compared with those who received Avastin plus placebo (hazard ratio=0.72; p=0.0012). Adverse events were consistent with previous Avastin or Tarceva NSCLC studies, or trials evaluating the two medicines together.


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.


"A second round of treatment following cancer progression is not an option for many patients with advanced NSCLC," said Vincent A. Miller, M.D., lead investigator of the ATLAS study, and Associate Attending Physician, Memorial Sloan-Kettering Cancer Center. "ATLAS showed that bevacizumab and erlotinib, when combined in the first-line maintenance setting, helped delay the growth or spread of the cancer."


"With this study we continue to build on the important advances Avastin has made in the first-line treatment of lung cancer," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. "It is our hope that adding the daily pill Tarceva to Avastin in the maintenance setting may potentially expand the options available for patients with advanced NSCLC who receive Avastin as an initial therapy."


Results of the ATLAS study were featured today during a press briefing at the 45th annual meeting of the American Society of Clinical Oncology (ASCO). Full results will be presented tomorrow by Dr. Miller (Abstract #LBA8002 - Sunday, May 31, 2009, 9:30 a.m. - 9:45 a.m. EDT, West Hall E1).


ATLAS is the second positive study that showed Tarceva in the first-line maintenance setting improved PFS. Another study, SATURN, showed patients who received Tarceva alone as a maintenance treatment following initial chemotherapy had a significant improvement in PFS, compared with placebo. Full results of SATURN will also be presented tomorrow (Abstract #8001 - Sunday, May 31, 2009, 9:15 a.m. - 9:30 a.m. EDT, West Hall E1).


Avastin is currently approved as first-line treatment in combination with carboplatin and paclitaxel chemotherapy for patients with locally advanced, non-squamous NSCLC. Tarceva is currently approved as a treatment for patients with advanced NSCLC whose disease has progressed after one or more courses of chemotherapy and can be used in patients with either non-squamous or squamous cell NSCLC. Both therapies have been shown to improve overall survival in these indications.


About ATLAS (AVF3671g)
ATLAS was a global, multicenter, randomized, double-blind, placebo-controlled study. Patients in the study were treated with Avastin plus four cycles of platinum-based chemotherapy. If the cancer did not progress and patients did not experience significant toxicity, patients (n=743) were then randomized to receive Avastin plus either Tarceva or placebo until progression. PFS, as assessed by investigators, was defined as the length of time from randomization to disease progression or death from any cause.


The 39 percent improvement in PFS observed in the study can also be referred to as a 28 percent reduction in the risk of cancer progression or death (hazard ratio=0.72; p=0.0012). Median PFS following four initial cycles of Avastin and chemotherapy was 4.8 months for patients who received the combination and 3.7 months for those who received Avastin plus placebo. Secondary endpoints included safety and overall survival. Overall survival data are expected in the second half of 2009.


Severe (Grade 3 to 4) adverse events were observed in 44 percent of patients receiving Avastin plus Tarceva and 30 percent of patients in the Avastin only arm. The most common Grade 3 to 4 adverse events that occurred in 5 percent or more of patients treated with Avastin plus Tarceva compared with patients in the Avastin only arm were rash (10.4 percent vs. 0.5 percent), diarrhea (9.3 percent vs. 0.8 percent), high blood pressure (5.4 percent vs. 5.7 percent) and fatigue (5.4 percent vs. 2.2 percent). There were eight deaths associated with adverse events in the group of patients treated with Avastin plus Tarceva, compared with four in the Avastin plus placebo group.


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 United States and approximately 160,000 Americans will die from the disease in 2009. NSCLC is the most common type of lung cancer.


About Tarceva
Tarceva is indicated as a single agent for patients with advanced 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/paclitaxel or gemcitabine/cisplatin) and its use is not recommended in that setting.


Tarceva Safety
There have been infrequent reports of serious Interstitial Lung Disease (ILD)-like events including deaths in patients taking Tarceva. Serious side effects (including deaths) in patients taking Tarceva include liver and/or kidney problems; gastrointestinal (GI) perforations (the development of a hole in the stomach, small intestine, or large intestine); and severe blistering skin reactions including cases similar to Stevens-Johnson syndrome. Patients taking Tarceva plus gemcitabine were more likely to experience bleeding and clotting problems such as heart attack or stroke. Eye irritation and damage to the cornea have been reported in patients taking Tarceva. Women should avoid becoming pregnant and avoid breastfeeding while taking Tarceva. Patients should call their doctor right away if they have these signs or symptoms: new or worsening skin rash, serious or ongoing diarrhea, nausea, loss of appetite, vomiting, stomach pain, new or worsening shortness of breath or cough, fever or eye irritation. Rash and diarrhea were the most common side effects associated with Tarceva in the non-small cell lung cancer clinical study.


For Tarceva full prescribing information, please visit http://www.tarceva.com.


About Avastin
Avastin is approved for the first- or second-line treatment of patients with 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 non-small cell lung cancer in combination with carboplatin and paclitaxel chemotherapy.


BOXED WARNINGS and Additional Important Safety Information
Patients treated with Avastin may experience side effects. In clinical trials, some patients treated with Avastin experienced serious side effects, including:


Gastrointestinal (GI) perforation:
Treatment with Avastin can result in the development of a 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 0.3 to 2.4 percent of patients and in some cases resulted in fatality. Avastin therapy should be permanently stopped in people with GI perforation.


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. In a clinical trial, 15 percent of patients with metastatic colorectal cancer who had surgery while receiving Avastin treatment had serious and fatal complications compared to 4 percent of patients who did not receive Avastin. Avastin should not be initiated for at least 28 days following surgery and until the surgical wound is fully healed. Avastin therapy should be permanently stopped in patients with wound healing problems that require medical treatment. The appropriate waiting time between stopping treatment with Avastin and having surgery has not been determined.


Severe bleeding:
Severe or fatal bleeding, including hemoptysis (coughing up of blood), GI bleeding, hematemesis (bloody vomit), central nervous system (CNS) hemorrhage (bleeding in the brain), epistaxis (nose bleeds), and vaginal bleeding occurred up to five-fold more frequently in patients receiving Avastin compared to patients receiving only chemotherapy. Across indications, Grade 3 or higher (severe or fatal) bleeding events have occurred in 1.2 to 4.6 percent of patients receiving Avastin. In patients with previously treated glioblastoma, intracranial hemorrhage (bleeding within the brain) occurred in eight of 163 patients and two people had Grade 3 to 4 (severe) bleeding. In patients treated with Avastin and chemotherapy for lung cancer, serious and sometimes fatal pulmonary hemorrhage (bleeding in the lungs) occurred in four of 13 (31 percent) patients with squamous cell histology, and two of 53 (4 percent) patients with non-squamous NSCLC compared with none of 32 (0 percent) patients treated with chemotherapy. People with serious bleeding or recent hemoptysis should not receive Avastin.


In clinical trials, additional serious side effects seen across different cancer types, in some cases resulting in fatality, included the following: formation of an abnormal passage from parts of the body to another part (non-GI fistula formation - less than 0.3 percent); stroke or heart problems (arterial thromboembolic events - 2.6 percent); high blood pressure (5 to 18 percent); nervous system and vision disturbances known as RPLS (reversible posterior leukoencephalopathy syndrome - less than 0.1 percent); severe infusion reactions (0.2 percent of people), and too much protein in the urine, and kidney damage (nephrotic syndrome - less than 1 percent).


The most common adverse reactions observed in Avastin patients at a rate of more than 10 percent and at least twice the control arm rate, were nose bleeds, headache, high blood pressure, irritation of the nose (rhinitis), protein in the urine, taste alteration, dry skin, rectal bleeding, tear production disorder (lacrimation), and inflammation of the skin (exfoliative dermatitis).


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.


For full Prescribing Information and Boxed WARNINGS on Avastin visit http://www.avastin.com.


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.


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