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Genentech Provides Update on Phase III MARIANNE Study in People with Previously Untreated Advanced HER2-Positive Breast CancerGenentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today top-line results of the Phase III MARIANNE study. The study evaluated three HER2-targeted regimens - Kadcyla® (ado-trastuzumab emtansine) plus Perjeta® (pertuzumab), Kadcyla alone, and Herceptin® (trastuzumab) plus taxane chemotherapy - in people with previously untreated (first-line) advanced HER2-positive breast cancer. The study showed the three regimens helped people live without their disease worsening (PFS) for a similar amount of time, meeting its non-inferiority endpoint as assessed by an Independent Review Committee. However, neither Kadcyla-containing treatment arm significantly improved PFS compared to Herceptin plus chemotherapy. Adverse events observed in the two experimental arms of the study were generally consistent with those seen in previous studies of Kadcyla and/or Perjeta. In their approved uses for advanced HER2-positive breast cancer, Kadcyla and Perjeta have been shown to extend survival. Kadcyla is approved for people with previously treated disease (second and later lines). Perjeta is approved in combination with Herceptin and chemotherapy for people with previously untreated disease (first line). "Over the past 30 years, we have made significant progress in treating one of the most aggressive forms of advanced breast cancer with medicines that extend patients' lives across the course of their disease. In this study, we had hoped to show improvement in progression-free survival without the use of traditional chemotherapy in the first-line treatment of patients with advanced HER2-positive breast cancer," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "While MARIANNE didn't achieve this result, we will continue to study these medicines, as well as investigational treatments for other types of breast cancer, with the goal of improving outcomes for patients." Data from the MARIANNE study will be presented at an upcoming medical meeting. Roche and Genentech will discuss the data with health authorities. About the MARIANNE Study The Phase III MARIANNE study (NCT01120184; BO22589) is an international, randomized, multicenter, three-arm study involving 1,095 people with advanced HER2-positive breast cancer - either with inoperable locally advanced disease that had worsened during or returned after previous treatment, or with disease that had spread to other areas of the body. People with advanced breast cancer at diagnosis and people whose disease had worsened following either neoadjuvant or adjuvant treatment were eligible. People enrolled in the study received treatment with either:
The primary endpoint of the MARIANNE study is PFS as assessed by an Independent Review Committee. Secondary endpoints include overall survival, response rate and the incidence of adverse events. Differences in these endpoints were assessed in each of the Kadcyla-containing treatment arms compared to the Herceptin plus chemotherapy arm, and also between the two Kadcyla-containing arms. About Kadcyla Kadcyla is an antibody-drug conjugate (ADC (News - Alert)) being studied in HER2-positive cancers. It is the first ADC to result from Genentech's 30 years of HER2 pathway research and the third medicine Genentech has developed for the treatment of HER2-positive breast cancer. Like Herceptin, Kadcyla binds to HER2-positive 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 Kadcyla is taken up by those cells, it is designed to destroy them by releasing the DM1 chemotherapy inside the cells. Genentech licenses technology for Kadcyla under an agreement with ImmunoGen, Inc. Kadcyla Indication Statement Kadcyla is approved for the treatment of people with HER2-positive metastatic breast cancer (MBC) who have received prior treatment with Herceptin and a taxane chemotherapy. People should either:
Important Safety Information Kadcyla is not the same medicine as trastuzumab (Herceptin). There are possible serious side effects of Kadcyla. The patient's doctor may do tests before starting Kadcyla and before each dose to monitor for these side effects. Kadcyla treatment may be stopped or the dose may be lowered if the patient experiences any of these side effects. Patients must contact their doctor right away if they experience any of these symptoms. Liver Problems
Heart Problems
Additional Possible Serious Side Effects of Kadcyla Lung Problems
Infusion-Related Reactions
Serious Bleeding
Low Platelet Count
Nerve Damage
Skin Reactions Around the Infusion Site
HER2 Testing and Kadcyla Patients must have a HER2 test to determine if their cancer is HER2-positive before taking Kadcyla, as benefit has only been shown in patients whose tumors are HER2-positive. Most Common Side Effects of Kadcyla The most common side effects seen in people taking Kadcyla were:
Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients and caregivers may also report side effects to Genentech at (888) 835-2555. For full Prescribing Information and Boxed WARNINGS on Kadcyla, please visit http://www.kadcyla.com. About Perjeta Perjeta is a medicine that targets the HER2 receptor, a protein found on the outside of many normal cells and in high quantities on the outside of cancer cells in HER2-positive cancers. Perjeta is designed specifically to prevent the HER2 receptor from pairing (or "dimerizing") with other HER receptors (EGFR/HER1, HER3 and HER4) on the surface of cells, a process that is believed to play a role in tumor growth and survival. Binding of Perjeta to HER2 may also signal the body's immune system to destroy the cancer cells. The mechanisms of action of Perjeta and Herceptin are believed to complement each other, as both bind to the HER2 receptor, but to different places. The combination of Perjeta and Herceptin is thought to provide a more comprehensive blockade of HER signaling pathways, thus preventing tumor cell growth and survival. Perjeta Indication Statement Perjeta is approved for use in combination with Herceptin and docetaxel chemotherapy in people who have HER2-positive breast cancer that has spread to different parts of the body (metastatic) and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer. Important Safety Information Most Serious Side Effects of Perjeta Perjeta may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure).
Receiving Perjeta during pregnancy can result in the death of an unborn baby and birth defects.
Perjeta should not be used in patients who are allergic to pertuzumab or to any of the ingredients in Perjeta. Other Possible Serious Side Effects
Perjeta has only been shown to work in people with HER2-positive breast cancer. Most Common Side Effects The most common side effects of Perjeta when given with Herceptin and docetaxel chemotherapy for treatment of breast cancer that has spread to other parts of the body (metastatic) are:
Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients and caregivers may also report side effects to Genentech at (888) 835-2555. Please see Perjeta full Prescribing Information including Most Serious Side Effects for additional Important Safety Information at http://www.perjeta.com. About Breast Cancer Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 235,000 people in the United States will be diagnosed with breast cancer, and 40,000 will die from the disease in 2014. In HER2-positive breast cancer, increased quantities of the Human Epidermal growth factor Receptor 2 (HER2) are present on the surface of the tumor cells. This is known as "HER2 positivity" and affects approximately 20-25 percent of people with breast cancer. HER2-positive cancer is a particularly aggressive form of breast cancer. About Genentech and Roche in HER2-positive Breast Cancer Genentech and Roche have spent more than 30 years studying the role of HER2 in cancer, and Perjeta and Kadcyla are a result of this research. A diagnostic test is used to determine if a person's tumor is HER2-positive and whether treatment with HER2-targeted medicines is appropriate. About Genentech Founded more than 35 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.
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