Thursday, Dec 18, 2014

Genentech Provides Update on Phase III MARIANNE Study in People with Previously Untreated Advanced HER2-Positive Breast Cancer

  • MARIANNE was designed to evaluate three HER2-targeted regimens in previously untreated (first-line) advanced HER2-positive breast cancer (Kadcyla alone, Kadcyla plus Perjeta, Herceptin plus chemotherapy)
  • Study met non-inferiority endpoint, showing similar progression-free survival (PFS) among the three arms
  • Study did not meet PFS superiority endpoint for Kadcyla-containing regimens
  • Results do not impact approved uses of Kadcyla or Perjeta in advanced HER2-positive breast cancer

South San Francisco, Calif. -- December 18, 2014 --

Genentech, 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:

  • A combination of Kadcyla and Perjeta
  • Kadcyla alone, or
  • Herceptin and either docetaxel or paclitaxel chemotherapy.

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) 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:

  • Have already been treated for their metastatic cancer, or
  •  Have had their early stage cancer come back during or within six months after they completed a course of treatment following surgery.


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

  • Kadcyla may cause severe liver problems that can be life-threatening. Symptoms of liver problems may include vomiting, eating disorder (anorexia), nausea, stomach pain, yellowing of the skin (jaundice), dark urine or itching.

Heart Problems

  • Kadcyla may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). Symptoms may include swelling of the ankles or legs, shortness of breath, cough, rapid weight gain of greater than five pounds in less than 24 hours, dizziness or loss of consciousness, or irregular heartbeat.

Pregnancy

  • Receiving Kadcyla during pregnancy can result in the death of an unborn baby and birth defects. Birth control should be used while patients receive Kadcyla and for six months after their last dose of Kadcyla.
  • If patients are exposed to Kadcyla during pregnancy, they must contact their healthcare provider right away; they are also encouraged to enroll in the MotHER Pregnancy Registry by contacting (800) 690-6720.
  • If patients are mothers who are breastfeeding, they should talk with their doctor about either stopping breastfeeding or stopping Kadcyla.


Additional Possible Serious Side Effects of Kadcyla

Lung Problems

  • Kadcyla may cause lung problems, including inflammation of the lung tissue, which can be life-threatening. Signs of lung problems may include trouble breathing, cough, tiredness and fluid in the lungs.

Infusion-Related Reactions

  • Symptoms of an infusion-related reaction may include one or more of the following: the skin getting hot or red (flushing), chills, fever, trouble breathing, low blood pressure, wheezing, tightening of the muscles in the chest around the airways or a fast heartbeat. The patient’s doctor will monitor the patient for infusion-related reactions.

Serious Bleeding

  • Kadcyla can cause life-threatening bleeding. Taking Kadcyla with other medications used to thin your blood (antiplatelet) or prevent blood clots (anticoagulation) can increase the risk of bleeding. The patient’s doctor should provide additional monitoring if the patient is taking one of these other drugs while on Kadcyla. Life-threatening bleeding may also happen with Kadcyla even when blood thinners are not also being taken.

Low Platelet Count

  • Low platelet count may happen during treatment with Kadcyla. Platelets are cells in the blood that help the blood clot.

Nerve Damage

  • Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, or muscle weakness or loss of muscle function. 

Skin Reactions Around the Infusion Site 

  • Kadcyla may leak from the vein or needle and cause reactions such as redness, tenderness, skin irritation, or pain or swelling at the infusion site. If this happens, it is more likely to happen within 24 hours of the infusion.

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:

  • Tiredness
  • Nausea
  • Pain that affects the bones, muscles, ligaments and tendons 
  • Bleeding
  • Low platelet count
  • Headache
  • Liver problems 
  • Constipation
  • Nosebleeds

 

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). 

  • A patient’s doctor may run tests to monitor the patient’s heart function before and during treatment with Perjeta.

Receiving Perjeta during pregnancy can result in the death of an unborn baby and birth defects.

  • Patients who think they may be pregnant should contact their healthcare provider immediately.
  • If patients are exposed to Perjeta during pregnancy, they are encouraged to enroll in the MotHER Pregnancy Registry by contacting (800) 690-6720.

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

  • Infusion-related reactions: Perjeta is a medicine that is delivered into a vein through a needle. This process can cause reactions known as infusion-related reactions. The most common infusion-related reactions when receiving Perjeta, Herceptin and docetaxel chemotherapy were feeling tired, abnormal or altered taste, allergic reactions, muscle pain and vomiting.
  • Severe allergic reactions: Some people receiving Perjeta may have severe allergic reactions, called hypersensitivity reactions or anaphylaxis. This reaction may be severe, may happen quickly and may affect many areas of the body.

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:

  • Diarrhea
  • Hair loss
  • Low levels of white blood cells with or without a fever
  • Nausea
  • Feeling tired
  • Rash
  • Damage to the nerves (numbness, tingling, pain in hands/feet)

 

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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