Thursday, May 14, 2009
South San Francisco, Calif. -- May 14, 2009 --Genentech, Inc. today provided an overview of results from studies involving the Genentech and Roche combined oncology portfolio that further the companies' approach to developing targeted medicines for people with cancer, a diagnosis that will affect nearly half of Americans during their lifetime. Results from studies involving Genentech's approved and investigational treatments will be presented during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) taking place May 29 through June 2 in Orlando, Fla.
Key study results to be presented at the meeting include:
"By focusing on the biology of cancer we are able to create potential new therapies that uniquely target the disease, impede multiple growth triggers and can be used at different times during the course of treatment,"?said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. "Biomarker research is involved in each of our cancer development programs in order to help us identify which patients may respond best to our medicines."
The combined Genentech and Roche worldwide oncology pipeline includes 27 new investigational agents in clinical studies.
Advances in HER-2 Targeted Therapy
Efficacy Results From the ToGA Trial: A Phase III Study of Trastuzumab Added to Standard Chemotherapy (CT) in First-Line Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer (GC) (Abstract #LBA4509) - Monday, June 1, 2009, 3:00 - 3:15 p.m. EST, West Hall D1
The Phase III study (ToGA) that showed patients with advanced HER2-positive stomach cancer lived longer when receiving Herceptin plus chemotherapy (Xeloda® [capecitabine]/intravenous 5-FU and cisplatin) compared to those who received chemotherapy alone. The study also showed how biomarker-guided therapy could provide potential future options for people with HER2-positive inoperable stomach cancer. Every year, one million people worldwide are diagnosed and 800,000 people die from stomach cancer. Data are under ASCO embargo and will be presented at the meeting.
A Phase II Study of Trastuzumab-DM1 (T-DM1), a HER2 Antibody-Drug Conjugate, in Patients With HER2-Positive Metastatic Breast Cancer: Final Results (Abstract #1017) - Saturday, May 30, 2009, 8:00 a.m. - 12:00 p.m. EST, West Hall E1
Final results from a Phase II study (TDM4258g) of T-DM1 in women whose disease had progressed following previous treatment with HER2-targeted therapies showed a decrease in tumor size (objective response rate) in 25 percent of women treated with T-DM1, as assessed by independent review (the primary endpoint of the study). The median follow-up time was 9.5 months. Sixty percent of patients had received prior treatment with Herceptin and lapatinib. T-DM1 is a novel antibody drug-conjugate that combines two approaches in one medicine: the Herceptin antibody links with a specialized cancer cell-killing agent, DM1, to deliver the agent directly to the cancer cell. The most common severe (Grade 3 or 4) adverse events were hypokalemia (lowered potassium levels) in 8 percent of patients and thrombocytopenia (lowered platelet levels) in 7 percent of patients. One adverse event leading to death was reported. No severe (Grade 3 or higher) cardiac-specific toxicity was observed.
This year Genentech initiated a Phase III study (EMILIA) evaluating T-DM1 for second-line advanced HER2-positive breast cancer. The company recently completed enrollment for another Phase II study in third-line advanced HER2-positive breast cancer for women who had progressed after treatment with lapatinib and Xeloda. Genentech licenses technology for T-DM1 under an agreement with ImmunoGen, Inc. Genentech has a significant program of antibody-conjugates consisting of various targets and in different stages of research and development.
Quantitative Assessment of HER2 Status and Correlation With Efficacy for Patients With Metastatic Breast Cancer in a Phase II Study of Trastuzumab-DM1 (T-DM1) (Abstract #1003) - Monday, June 1, 2009, 10:30 - 10:45 a.m. EST, West Hall D2
A separate analysis from TDM4258g showed that women with HER2-positive tumors had an increased response to T-DM1 compared to those with HER2-negative tumors. While all women enrolled were diagnosed with HER2-positive cancer, the study used standard HER2 testing methodologies, such as FISH (fluorescence in situ hybridization) and IHC (immunohistochemistry), as well as newer HER2 testing methodology known as mRNA quantitative real-time polymerase chain reaction (qRT-PCR) to conduct central confirmation of HER2 status.
New Approaches to Treating Lung Cancer
ATLAS: A Randomized, Double-Blind, Placebo-Controlled, Phase IIIb Trial Comparing Bevacizumab Therapy With or Without Erlotinib After Completion of Chemotherapy With Bevacizumab for First-Line Treatment of Locally-Advanced, Recurrent or Metastatic Non-Small Cell Lung Cancer (Abstract #LBA8002) - Sunday, May 31, 2009, 9:30 - 9:45 a.m. EST, West Hall E1
ATLAS, a Phase III study, showed patients with advanced NSCLC lived longer without their cancer getting worse when the daily pill Tarceva was added to Avastin in the first-line maintenance setting compared to Avastin alone, following initial treatment with Avastin plus chemotherapy. Full results are under ASCO embargo and will be presented at the meeting.
SATURN: A Double-Blind, Randomized, Phase III Study of Maintenance Erlotinib Versus Placebo Following Non-Progression With First-Line Platinum-Based Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer (Abstract #8001) - Sunday, May 31, 2009, 9:15 a.m. - 9:30 a.m. EST, West Hall E1
Data from the Phase III SATURN study showed patients with advanced NSCLC who received Tarceva as a first-line maintenance treatment had a 41 percent improvement in the time they lived without the disease advancing (progression-free survival or PFS, a primary endpoint of the study) compared to placebo (hazard ratio=0.71; 29 percent reduction in the risk of cancer progression or death). Median PFS was 12.3 weeks for patients who received Tarceva and 11.1 weeks for those who received placebo.
In the study, patients were treated with four cycles of platinum-based chemotherapy and then randomized to Tarceva or placebo if cancer did not progress. PFS was defined as the length of time from randomization to disease progression or death. Overall survival data for this study are not yet mature and are expected in the second half of this year.
A co-primary endpoint of the study was PFS in the subset of patients whose tumors over-expressed the epidermal growth factor receptor (EGFR) as assessed by IHC test. The study showed these patients had a 45 percent improvement in PFS if they received Tarceva compared to placebo (hazard ratio=0.69; 31 percent reduction in the risk of cancer progression or death).
Importantly, Tarceva showed a PFS improvement in patients with different types of lung cancer including squamous or non-squamous cell NSCLC. A sub-set analysis showed that patients with squamous cell NSCLC who received Tarceva had a 32 percent improvement in PFS and those with non-squamous cell NSCLC had a 47 percent improvement compared with placebo (squamous: hazard ratio=0.76; non-squamous: hazard ratio=0.68). Patients with adenocarcinoma, the most common type of non-squamous cell NSCLC lung cancer, had a PFS improvement of 67 percent (hazard ratio=0.60).
There were no new or unexpected safety signals in the study. The most commonly reported adverse events in patients who received Tarceva were rash (49 percent, 213/438) and diarrhea (20 percent, 88/438).
Biomarker Analyses From the Phase III Placebo-Controlled SATURN Study of Maintenance Erlotinib Following First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer (Abstract #8020) - Monday, June 1, 2009, 8:00 a.m. - 12:00 p.m. EST, W340A
Pre-planned analyses from SATURN provided valuable information on the potential role of certain biomarkers in predicting benefit with Tarceva and contribute to the growing body of information on the significance of biomarkers in lung cancer.
Patients who received Tarceva had a PFS benefit regardless of EGFR overexpression status as evaluated by IHC or FISH, and regardless of EGFR or K-ras mutation status. However, patients who received Tarceva and whose tumors had an EGFR mutation (11 percent) had a 10-fold improvement in PFS compared to placebo (hazard ratio=0.10).
Avastin in Early-Stage Colon Cancer
C-08: A Phase III Trial Comparing mFOLFOX6 to mFOLFOX6 Plus Bevacizumab in Stage II or III Carcinoma of the Colon: Results of NSABP Protocol C-08 (Abstract #LBA4) - Sunday, May 31, 2009, 3:15 - 3:30 p.m. EST, West Hall D2
Full results from the first trial of Avastin in early-stage colon cancer (known as NSABP C-08) are under ASCO embargo and will be presented at the meeting. Although the study did not meet its primary endpoint of improving disease free survival, an initial review of the data suggests Avastin may be active in patients with early-stage colon cancer. The ongoing adjuvant program in colon, breast and lung cancers involves more than 26,000 patients. This includes the second Phase III study of Avastin in early-stage colon cancer (AVANT) with results expected in 2010.
C-08 and ATLAS are two of 10 oral presentations on Avastin at the meeting. Results will also be presented for mid-stage studies in other types of cancer. Avastin is being studied in more than 450 clinical studies worldwide and more than 30 different tumor types.
Herceptin is approved for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature) breast cancer:
Herceptin is also approved for metastatic breast cancer:
Herceptin administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure and decreased left ventricular ejection fraction. Serious infusion reactions and pulmonary toxicity have occurred; fatal infusion reactions have been reported. Exacerbation of chemotherapy-induced neutropenia has also occurred. The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia and myalgia.
For Herceptin full prescribing information, including Boxed WARNINGS and additional important safety information, please visit http://www.herceptin.com.
Tarceva monotherapy is approved for the treatment of patients with locally advanced or metastatic non-small cell lung cancer 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.
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, or stomach pain; new or worsening shortness of breath or cough; fever; eye irritation. Rash and diarrhea were the most common side effects associated with Tarceva in the non-small cell lung cancer clinical study. Fatigue, rash, nausea, loss of appetite, and diarrhea were the most common side effects associated with Tarceva plus gemcitabine therapy in the pancreatic cancer clinical study.
For Tarceva full prescribing information, please visit http://www.tarceva.com.
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.
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. 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. 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. Some people receiving Avastin with chemotherapy for lung cancer experienced hemoptysis. In some cases, this event resulted in fatality. 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, which may be a sign of kidney problems, was increased.
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 Avastin full prescribing information, including Boxed WARNINGS and additional important safety information, please visit http://www.avastin.com.
Xeloda is the only FDA-approved oral chemotherapy for both metastatic breast cancer and adjuvant (Dukes C) and metastatic colorectal cancer. Inactive in pill form, Xeloda is enzymatically activated within the body; when it comes into contact with a naturally occurring protein called thymidine phosphorylase, or TP, Xeloda is transformed into 5-FU, a cytotoxic (cell-killing) drug. Because many cancers have higher levels of TP than normal tissue, more 5-FU is delivered to the tumor than to other tissue.
A clinically important drug interaction between Xeloda and warfarin has been demonstrated; altered coagulation parameters and/or bleeding and death have been reported. Clinically significant increases in prothrombin time (PT) and INR have been observed within days to months after starting Xeloda, and in a few cases, within one month of stopping Xeloda. For patients receiving both drugs concomitantly, frequent monitoring of INR or PT is recommended. Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy.
Xeloda is contraindicated in patients who have a known hypersensitivity to 5-fluorouracil, and in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. Xeloda is contraindicated in patients with severe renal impairment. For patients with moderate renal impairment, dose reduction is required.
Most common adverse reactions (30%) were diarrhea, hand-and-foot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, and hyperbilirubinemia. Other adverse reactions, including serious adverse reactions, have been reported. As with any cancer therapy, there is a risk of side effects, and these are usually manageable and reversible with dose modification or interruption.
For Xeloda full prescribing information, visit http://www.xeloda.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, Calif. For additional information about the company, please visit http://www.gene.com.