Genentech’s Perjeta Significantly Extends Survival in People With HER2-Positive Metastatic Breast Cancer

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced updated survival results from the Phase III CLEOPATRA study, which showed that the combination of Perjeta® (pertuzumab), Herceptin® (trastuzumab) and docetaxel chemotherapy significantly extended the lives (overall survival) of people with previously untreated HER2-positive metastatic breast cancer (mBC), compared to Herceptin, chemotherapy and placebo. Results showed that the risk of death was reduced by 34 percent for people who received Perjeta, Herceptin and chemotherapy, compared to those who received Herceptin and chemotherapy (HR=0.66; p=0.0008). At the time of the analysis, median overall survival had not yet been reached in people receiving the Perjeta combination, as more than half of these people continued to survive. Median overall survival was more than three years (37.6 months) for people who received Herceptin and chemotherapy. Based on these data, people receiving Herceptin and chemotherapy in CLEOPATRA have been offered the option to receive Perjeta. No new safety signals were observed in the study.

“This treatment combination with Perjeta is the first to have significantly extended survival compared to Herceptin and chemotherapy in people with previously untreated HER2-positive metastatic breast cancer,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “These data further demonstrate that Perjeta is an important new medicine for people with this aggressive disease.”

Perjeta is a personalized medicine that targets the HER2 receptor, a protein found in high quantities on the outside of cancer cells in HER2-positive cancers. Perjeta is believed to work in a way that is complementary to Herceptin, as the two medicines target different places on the HER2 receptor.

In June 2012, the U.S. Food and Drug Administration (FDA) approved Perjeta in combination with Herceptin and docetaxel chemotherapy for the treatment of people with HER2-positive mBC who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease, based on the results of the CLEOPATRA study. Perjeta was approved by Swissmedic in August 2012 and in Mexico in September 2012 for the treatment of people with HER2-positive mBC who have not received prior therapy for their metastatic disease. Roche has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Perjeta for people with previously untreated HER2-positive mBC.

These final, confirmatory survival data from the CLEOPATRA study will be presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS), Friday, December 7, 2012 (Abstract #P5-18-26, 5-7pm CT, Exhibit Hall A-B) by Dr. Sandra Swain, Medstar Washington Hospital Center.

About the CLEOPATRA Study

CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) is an international, Phase III, randomized, double-blind, placebo-controlled study. The study evaluated the efficacy and safety profile of Perjeta combined with Herceptin and docetaxel chemotherapy compared to Herceptin and docetaxel chemotherapy plus placebo in 808 people with previously untreated HER2-positive mBC or with HER2-positive mBC that had come back after prior therapy in the adjuvant or neoadjuvant setting.

The primary endpoint of the study was progression-free survival (PFS) as assessed by an independent review committee. Secondary endpoints were overall survival, PFS by investigator assessment, safety profile, overall response rate (ORR), duration of response and time to symptom progression. PFS and safety data from CLEOPATRA were presented at SABCS 2011 and simultaneously published in the New England Journal of Medicine.

PFS and Safety Results:

• People who received the combination of Perjeta, Herceptin and chemotherapy had a statistically significant 38 percent reduction in the risk of their disease worsening or death (PFS, HR=0.62; p<0.0001) compared to people who received Herceptin, chemotherapy and placebo.
• The median PFS improved by 6.1 months from 12.4 months for people who received Herceptin and chemotherapy to 18.5 months for those who received Perjeta, Herceptin and chemotherapy.
• The most common adverse events (AEs, rate greater than 30 percent) seen with the combination of Perjeta, Herceptin and chemotherapy were diarrhea, hair loss, low white blood cell count with or without fever, upset stomach, fatigue, rash and peripheral neuropathy (numbness, tingling or damage to the nerves). The most common Grade 3–4 AEs (rate greater than 2 percent) were low white blood cell count with or without fever, decrease in a certain type of white blood cell, diarrhea, damage to the nerves, decrease in red blood cell count, weakness and fatigue.

About Perjeta

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, Herceptin and docetaxel chemotherapy is thought to provide a more comprehensive blockade of HER signaling pathways.

Genentech and Roche have spent more than 30 years studying the role of HER2 in cancer, and Perjeta is a result of this research. A companion diagnostic test is used to determine if a person is HER2-positive and whether treatment with Perjeta and Herceptin is appropriate.

Perjeta Indication Statement

Perjeta® (pertuzumab) is approved for use in combination with Herceptin® (trastuzumab) and docetaxel chemotherapy in people with 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 disease.

Important Safety Information

• Because side effects from this treatment are common, it is important to know what side effects may happen and what symptoms patients should watch for
• A patient’s doctor may stop treatment if serious side effects happen. Patients must contact their healthcare team right away if they have questions or are worried about any side effects

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

• Birth control should be used while receiving Perjeta and for six months after a patient’s last dose of Perjeta. Patients who are breastfeeding should talk with their doctor about either stopping breastfeeding or stopping Perjeta
• If a patient thinks she may be pregnant, she should contact her healthcare provider immediately
• If a patient is exposed to Perjeta during pregnancy, she is encouraged to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720

Other Possible Serious Side Effects

• Heart problems: Perjeta 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). A patient’s doctor may run tests to monitor the patient’s heart function before and during treatment with Perjeta
• 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 been shown to work only in people with HER2-positive breast cancer. Patients must have a HER2 test to know if their breast cancer is HER2-positive before receiving an anti-HER2 treatment, such as Perjeta

Most Common Side Effects

The most common side effects of Perjeta when given with Herceptin and docetaxel chemotherapy 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 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 Effect for additional Important Safety Information.

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.

Herceptin has two approved uses in metastatic breast cancer (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 regimens 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 Breast Cancer

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 229,000 people will be diagnosed with breast cancer, and 40,000 will die from the disease in 2012. 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 25 percent of people with breast cancer. HER2-positive cancer is a particularly aggressive form of breast cancer.

About Genentech Access Solutions

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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.