Genentech Will Report New Data on Important Progress for People with Advanced Cancers at ASCO 2012
-- First Pivotal Phase III Data on Genentech's Antibody-Drug Conjugate Trastuzumab Emtansine (T-DM1) in Advanced HER2-Positive Metastatic Breast Cancer --
-- Phase III Data on Avastin in Advanced Colorectal and Ovarian Cancers --
South San Francisco, Calif. -- May 15, 2012 -- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the company will present important new data from studies of several of its cancer medicines at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO), June 1 to 5, 2012, in Chicago. At the meeting, data on Genentech's late-stage investigational and approved cancer medicines will be communicated in sessions that include 30 oral presentations.
"We have made significant progress for people with advanced cancers in the past year," said Hal Barron M.D., chief medical officer and head, Global Product Development. "At ASCO, we're pleased to present new data showing how we are moving forward in our goal of helping people who need new options in their fight against a number of advanced cancers, including data from EMILIA, our pivotal Phase III study on trastuzumab emtansine in HER2-positive metastatic breast cancer."
Key Study Results to be Presented Include:
- Trastuzumab emtansine (T-DM1): Pivotal Phase III data (EMILIA) in people with HER2-positive metastatic breast cancer (mBC) who had previously received treatment with Herceptin and a taxane (chemotherapy) will be presented for the first time. These data will be submitted to global health authorities later this year. EMILIA will be presented in the plenary session at ASCO and will also be highlighted as part of ASCO's official press program.
- Avastin® (bevacizumab): Data will be presented from a Phase III study (ML18147) evaluating Avastin in combination with chemotherapy in people with metastatic colorectal cancer (mCRC) whose disease worsened following initial treatment with Avastin and a different chemotherapy. This study will be highlighted as part of ASCO's official press program.
- Data from AURELIA, the first Phase III study of Avastin plus chemotherapy in people with platinum-resistant recurrent ovarian cancer will be presented. This study will be highlighted as part of ASCO's official press program.
- Zelboraf® (vemurafenib): Updated overall survival results will be presented based on the most recent analysis from BRIM3, a Phase III study in people with previously untreated BRAF V600E mutation-positive unresectable or metastatic melanoma.
First Phase III Data on Trastuzumab Emtansine in Advanced HER2-Positive mBC
The introduction of Herceptin, the first targeted medicine for HER2-positive mBC, was a significant milestone for people with this aggressive breast cancer. However, additional effective medicines are still needed for this fatal disease. The Phase III EMILIA study evaluated trastuzumab emtansine in people with HER2-positive mBC who had previously received Herceptin and a taxane. As previously announced, the study showed that people who were treated with trastuzumab emtansine lived significantly longer without their disease getting worse (progression-free survival or PFS) compared to those who received lapatinib plus Xeloda® (capecitabine). The safety profile of trastuzumab emtansine in the study was consistent with that seen in previous studies.
EMILIA: Primary results from EMILIA, a phase 3 study of trastuzumab emtansine (T-DM1) vs. capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane. Abstract #LBA1. ASCO press briefing Saturday, June 2. Oral plenary presentation, Sunday, June 3, 1:45 PM - 2:00 PM CDT in N Hall B1.
Phase III Data on Avastin in Advanced Colorectal and Ovarian Cancers
Data will be presented from the Phase III ML18147 study. As previously announced, this study showed that people with mCRC who received Avastin plus standard chemotherapy as initial treatment ("first-line") and then continued on Avastin with a different chemotherapy after their cancer worsened ("second-line") lived significantly longer (overall survival or OS) than people who received chemotherapy only second-line. No new safety findings were observed and adverse events were consistent with those seen in previous trials of Avastin in mCRC.
ML18147: Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV + CT: Results of a randomized Phase III intergroup study. Abstract #CRA3503. ASCO press briefing Saturday, June 2. Oral presentation, Sunday, June 3, 10:45 AM - 11:00 AM CDT in E Hall D1.
Advanced ovarian cancer is an aggressive disease that unfortunately gets worse for many women even after initial treatment and, for some, the disease will become resistant to platinum-based chemotherapy. For these women, there are only limited treatment options available. The AURELIA study is the first Phase III study to evaluate the efficacy and safety profile of Avastin when added to chemotherapy in women with previously treated (recurrent) platinum-resistant ovarian cancer.
AURELIA: A randomized Phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC). Abstract #LBA5002. ASCO press briefing Friday, June 1. Oral presentation, Saturday, June 2, 3:30 PM - 3:45 PM CDT in E354b.
Updated Overall Survival Data on Zelboraf for People With Metastatic Melanoma
Updated OS data will be shared for Zelboraf, the first and only approved personalized skin cancer medicine for patients with BRAF V600E mutation-positive unresectable or metastatic melanoma as confirmed by an FDA-approved test.
BRIM3: Updated overall survival (OS) results for BRIM3, a Phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib (vem) with dacarbazine (DTIC) in previously untreated patients with BRAF V600E mutated melanoma. Abstract #8502. Oral presentation, Monday, June 4, 8:30 AM - 8:45 AM, CDT in E Arie Crown Theater.
Full session details of the 2012 Annual Meeting can be found through the ASCO ePlanner.
About Trastuzumab Emtansine
Trastuzumab emtansine (T-DM1) is an investigational antibody-drug conjugate (ADC) being studied in HER2-positive cancers. Trastuzumab emtansine is designed to inhibit HER2 signaling and deliver the chemotherapy agent DM1 directly inside HER2-positive cancer cells. Trastuzumab emtansine binds to HER2-positive cancer cells and is thought to block out-of-control signals that make the cancer grow while also calling on the body's immune system to attack the cancer cells. Once trastuzumab emtansine is absorbed into those cancer cells, it is designed to destroy them by releasing the DM1. Building on the results of trastuzumab emtansine studies to date, Roche and Genentech have approximately 30 ADCs in the pipeline.
Genentech licenses technology for trastuzumab emtansine under an agreement with ImmunoGen, Inc.
About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor blood supply is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). For more information about angiogenesis, visit http://www.gene.com.
Avastin is approved for first- or second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy.
BOXED WARNINGS and Additional Important Safety Information
People receiving Avastin may experience side effects. In clinical trials, some people treated with Avastin experienced serious and sometimes fatal 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 event occurred in more people who received Avastin than in the comparison group (2.4 percent to 0.3 percent). In some cases, GI perforation resulted in fatality. Avastin therapy should be permanently stopped if GI perforation occurs.
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. Surgery and wound healing problems occurred more often in people who received Avastin than in the comparison group. In a controlled clinical trial, in patients with metastatic colorectal cancer who had surgery during the course of treatment, the incidence of wound healing complications, including serious and fatal complications, was 15 percent for patients who received Avastin and four percent for patients who did not receive Avastin.
Avastin therapy should not be started for at least 28 days after surgery and until the surgical wound is fully healed. The length of time between stopping Avastin and having voluntary surgery without the risk of wound healing problems following surgery has not been determined. Treatment with Avastin should be stopped at least 28 days before voluntary surgery and in people with wound healing problems following surgery that require medical treatment. Treatment with Avastin should be stopped in patients with slow or incomplete wound healing.
Severe bleeding: Treatment with Avastin can result in serious or fatal bleeding, including coughing up blood, bleeding in the stomach, vomiting of blood, bleeding in the brain, nosebleeds and vaginal bleeding. These events occurred up to five times more often in people who received Avastin compared to patients who received only chemotherapy. Across cancer types, 1.2 percent to 4.6 percent of people who received Avastin experienced severe to fatal bleeding. People who have recently coughed up blood (greater than or equal to a half teaspoon of red blood) or have serious bleeding should not receive Avastin. Treatment with Avastin should be permanently stopped if serious bleeding occurs.
In clinical trials for different cancer types, there were additional serious and sometimes fatal side effects that occurred in more people who received Avastin than in those in the comparison group. The formation of an abnormal passage from parts of the body to another part (non-GI fistula formation) was seen in 0.3 percent or less of people. Severe to life-threatening stroke or heart problems were seen in 2.6 percent of people. Too much protein in the urine that led to kidney problems was seen in less than one percent of people. Additional serious side effects that occurred in more people who received Avastin than those in the comparison group included severe to life-threatening high blood pressure, which was seen in five percent to 18 percent of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.1 percent of people. Infusion reactions with the first dose of Avastin were uncommon and occurred in less than three percent of people, and severe reactions occurred in 0.2 percent of people. Avastin can cause fertility issues for women. Avastin could cause a woman¿s ovaries to stop working and may impair her ability to have children.
Common side effects that occurred in more than 10 percent of people who received Avastin for different cancer types, and at least twice the rate of the comparison group, were nosebleeds, headache, high blood pressure, inflammation of the nose, too much protein in the urine, taste change, dry skin, rectal bleeding, tear production disorder, back pain and inflammation of the skin (exfoliative dermatitis). Across all trials, treatment with Avastin was permanently stopped in 8.4 percent to 21 percent of people because of side effects.
Patients who are pregnant or thinking of becoming pregnant should talk with their doctor about the potential risk of loss of the pregnancy or the potential risk of Avastin to the fetus during and following Avastin therapy, and the need to continue an effective birth control method for at least six months following the last dose of Avastin.
Women should be advised to discontinue nursing or discontinue treatment with Avastin, taking into account the importance of Avastin to the mother.
First-line Metastatic Colorectal Cancer
In the first-line metastatic colorectal cancer trial, the most common severe to life-threatening side effects that increased by two percent or more in people who received Avastin plus IFL chemotherapy vs. IFL alone were weakness (10 percent vs. 7 percent), abdominal pain (8 percent vs. 5 percent), pain (8 percent vs. 5 percent), high blood pressure (12 percent vs. 2 percent), blood clots in the veins of the body (9 percent vs. 5 percent), blood clots inside the abdomen (3 percent vs. 1 percent), a brief loss of consciousness (3 percent vs. 1 percent), diarrhea (34 percent vs. 25 percent), constipation (4 percent vs. 2 percent), reduced white blood cell counts (37 percent vs. 31 percent) and reduced white blood cell counts that may increase the chance of infection (21 percent vs. 14 percent).
Second-line Metastatic Colorectal Cancer
In the second-line metastatic colorectal cancer trial, the most common severe to life-threatening and fatal side effects that increased by two percent or more in people who received Avastin plus FOLFOX4 chemotherapy vs. FOLFOX4 alone were diarrhea (18 percent vs. 13 percent), nausea (12 percent vs. 5 percent), vomiting (11 percent vs. 4 percent), dehydration (10 percent vs. 5 percent), blockage of the bowel (4 percent vs. 1 percent), numbness and tingling in fingers and toes (17 percent vs. 9 percent), nervous system disturbances (5 percent vs. 3 percent), tiredness (19 percent vs. 13 percent), abdominal pain (8 percent vs. 5 percent), headache (3 percent vs. 0 percent), high blood pressure (9 percent vs. 2 percent) and severe bleeding (5 percent vs. 1 percent).
For full Prescribing Information and Boxed WARNINGS on Avastin please visit http://www.avastin.com.
About Herceptin
Herceptin is a personalized medicine designed to specifically block the HER2 protein on the surface of some cancer cells. Based on preclinical studies, this biologic antibody is believed to work by attaching to HER2 receptors to stop signals that make the tumor cells grow and divide, and also by signaling the body's immune system to destroy the cancer cells.
Adjuvant Breast Cancer:
Herceptin is approved for the treatment of early-stage breast cancer that is HER2-positive and has spread into the lymph nodes, or is HER2-positive and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high risk feature.* Herceptin can be used in several different ways:
As part of a treatment course including the chemotherapy drugs doxorubicin, cyclophosphamide and either paclitaxel or docetaxel. This treatment course is known as "AC→TH."
With the chemotherapy drugs docetaxel and carboplatin. This treatment course is known as "TCH."
Alone after treatment with multiple other therapies, including an anthracycline-based therapy (a type of chemotherapy).
*High risk is defined as ER/PR-positive with one of the following features: tumor size greater than 2 cm, age less than 35 years or tumor Grade 2 or 3.
Metastatic Breast Cancer:
Herceptin has two approved uses in mBC:
Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first-line treatment of HER2-positive mBC.
Herceptin alone is approved for the treatment of HER2-positive mBC in patients who have received one or more chemotherapy courses for metastatic disease.
Important Safety Information
Herceptin treatment can result in heart problems, including for those patients without symptoms (such as reduced heart function) and those patients with symptoms (such as congestive heart failure). One patient died in an adjuvant breast cancer trial from significantly weakened heart muscle. The risk and seriousness of these heart problems were highest in patients who received both Herceptin and a certain type of chemotherapy (anthracycline).
Before taking the first dose of Herceptin and during treatment, a patient's doctor should check to see if there are any health conditions that may increase the patient's chance of having serious heart problems. This includes a review of the patient's health history and tests to see how well the heart muscle is working. These tests may include an echocardiogram or a multigated acquisition (MUGA) scan. Some early-stage breast cancer patients may also need to have a test done after they have finished taking Herceptin to see how well their heart muscle is working.
Some patients have had serious infusion reactions and lung problems; fatal infusion reactions have been reported. These reactions usually occur during or within 24 hours of receiving Herceptin.
The patient's doctor may need to completely stop Herceptin treatment if the patient has a severe allergic reaction, swelling, lung problems, inflammation of the lung or severe shortness of breath.
Herceptin can cause harm to the fetus (unborn baby), and in some cases death to the fetus, when taken by a pregnant woman. Women who could become pregnant need to use effective birth control methods during Herceptin treatment and for at least six months after treatment with Herceptin. Nursing mothers treated with Herceptin should discontinue nursing or discontinue Herceptin.
Worsening of low white blood cell counts associated with chemotherapy has also occurred.
Patients must have a HER2 test to determine if their breast cancer is HER2-positive before using Herceptin, as benefit has only been shown in patients who are HER2-positive.
The most common side effects associated with Herceptin in patients with breast cancer are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cells and muscle pain.
Because everyone is different, it is not possible to predict what side effects any one patient will have. Patients with questions or concerns about side effects should talk to their doctor.
Patients should read the Herceptin Full Prescribing Information including Boxed WARNINGS, at http://www.herceptin.com.
About Zelboraf
Zelboraf is a prescription medicine that is an oral, small molecule, kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Zelboraf is not recommended for use in melanoma patients who lack the BRAF V600E mutation.
Zelboraf is being co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon, a member of the Daiichi Sankyo Group. Genentech and Daiichi Sankyo, Inc. co-promote Zelboraf in the United States.
Important Safety Information for Zelboraf
Zelboraf may cause a type of skin cancer called cutaneous squamous cell carcinoma (cuSCC) that usually does not spread to other parts of the body. Patients should check their skin and tell their doctor about skin changes including a new wart, a skin sore or reddish bump that bleeds or does not heal, or a mole that changes size or color.
While taking Zelboraf, patients should avoid going out in the sun. When patients go outside, they should wear clothes that protect their skin, including head, face, hands, arms and legs. They should use lip balm and a broad-spectrum sunscreen with SPF 30 or higher.
Allergic reactions can happen while taking Zelboraf, and may be severe.
Patients must stop taking Zelboraf and get medical help if they have any of these symptoms: a rash or redness all over the body; feel faint; have trouble breathing or swallowing; have throat tightness or hoarseness; have a fast heartbeat; have swelling of the face, lips or tongue.
Patients must stop taking Zelboraf and call their doctor right away if they get a skin rash with any of the following symptoms because they may have a severe skin reaction: blisters on the skin; blisters or sores in the mouth; peeling of the skin; fever; redness or swelling of the face, hands or soles of the feet.
Patients must tell their doctor right away if they feel faint, lightheaded, dizzy, or feel their heart beating irregularly or fast while taking Zelboraf. These may be symptoms related to QT prolongation, a change in the electrical activity of the heart, which can be potentially life-threatening.
Patients must tell their doctor right away if they get any of these symptoms of a liver problem during treatment: skin or the whites of the eyes turn yellow; feel tired; urine turns dark or brown (tea color); nausea or vomiting; do not want to eat; pain on the right side of the stomach.
Patients must tell their doctor right away if they get these symptoms during treatment with Zelboraf: eye pain, swelling, or redness, blurred vision or other vision changes during treatment with Zelboraf.
Patients may develop new melanoma lesions while taking Zelboraf. Patients should check their skin and tell their doctor right away about any skin changes.
Common side effects of Zelboraf include joint pain, rash, hair loss, tiredness, sunburn or sun sensitivity, nausea, itching, or warts.
These are not all of the possible side effects of Zelboraf. Patients must tell their doctor if they have any side effect that bothers them or does not go away. For more information about side effects, patients should ask their doctor or pharmacist.
For full Prescribing Information and Medication Guide for additional important safety information for Zelboraf, please visit http://www.zelboraf.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 member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.