Wednesday, Mar 1, 2017

Phase III APHINITY Study Shows Genentech’s Perjeta® Regimen Helped People with an Aggressive Type of Early Breast Cancer Live Longer without their Disease Returning Compared to Herceptin® and Chemotherapy

Perjeta plus Herceptin and chemotherapy showed a statistically significant improvement in invasive disease-free survival (iDFS) for people with HER2-positive early breast cancer (EBC) compared to Herceptin and chemotherapy alone

Data will be discussed with health authorities, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)

South San Francisco, CA -- March 1, 2017 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), the Breast International Group (BIG), Breast European Adjuvant Study Team (BrEAST) and Frontier Science Foundation (FS) today announced positive results from the Phase III APHINITY study. The study met its primary endpoint and showed that adjuvant (after surgery) treatment with the combination of Perjeta® (pertuzumab), Herceptin® (trastuzumab) and chemotherapy (the Perjeta-based regimen) achieved a statistically significant reduction in the risk of recurrence of invasive disease or death (invasive disease-free survival; iDFS) in people with HER2-positive early breast cancer (EBC) compared to Herceptin and chemotherapy alone. The safety profile of the Perjeta-based regimen was consistent with that seen in previous studies, and no new safety signals were identified. Full results from the APHINITY trial will be presented at an upcoming medical meeting in 2017.

“These results from the positive APHINITY study represent an important addition to the body of data for Perjeta in the treatment of people with HER2-positive early breast cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We look forward to discussing these adjuvant results with global regulatory authorities.”

Gunter von Minckwitz, M.D., study coordinator from the Breast International Group and academic study partners, added, “APHINITY provides yet another example of the importance of industry-academic collaborations and their value in advancing cancer care for people affected by this challenging disease.”

HER2-positive breast cancer is an aggressive form of the disease, which affects approximately one in five people with breast cancer and is associated with a poor prognosis if left untreated. Despite advancements in the treatment of HER2-positive EBC, up to one in three people treated with Herceptin and chemotherapy may eventually see their cancer return. Treatment options are needed to improve the outcomes of people with this aggressive disease. Treating breast cancer early, before it has spread, may improve the chance of preventing the disease from returning and potentially reaching an incurable stage. Adjuvant therapy is given after surgery and is aimed at killing any remaining cancer cells to reduce the risk of the cancer returning.

In the U.S., the combination of Perjeta, Herceptin and docetaxel chemotherapy is currently available under accelerated approval for neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node-positive) as part of a complete treatment regimen for early breast cancer. This approval is based primarily on data from a Phase II study showing that nearly 40 percent of people receiving the combination of Perjeta, Herceptin and docetaxel chemotherapy had no evidence of microscopic tumor tissue detectable at the time of surgery (known as a pathological complete response, or pCR) compared to almost 22 percent in the Herceptin and docetaxel chemotherapy arm. The APHINITY trial reflects the commitment to evaluate the Perjeta-based regimen as part of a complete treatment approach for EBC. These data will be discussed with the FDA with the hope to convert the current accelerated approval to a full approval.

About APHINITY

APHINITY (Adjuvant Pertuzumab andHerceptin IN Initial TherapY in Breast Cancer, NCT01358877/ BO25126/ BIG 4-11) is an international, Phase III, randomized, double-blind, placebo-controlled, two-arm study evaluating the efficacy and safety of Perjeta plus Herceptin and chemotherapy compared to Herceptin and chemotherapy as an adjuvant therapy in 4,805 people with operable HER2-positive EBC.

People enrolled in the study underwent surgery and were randomized to one of two arms (1:1) to receive either:

  • Six to eight cycles of chemotherapy (anthracycline or non-anthracycline-containing regimen) with Perjeta and Herceptin, followed by Perjeta and Herceptin every three weeks for a total of one year (52 weeks) of treatment.
  • Six to eight cycles of chemotherapy (anthracycline or non-anthracycline-containing regimen) with placebo and Herceptin, followed by placebo and Herceptin every three weeks for a total of one year (52 weeks) of treatment.

Radiotherapy and/or endocrine therapy could be initiated at the end of adjuvant chemotherapy. The APHINITY study allowed for a range of standard chemotherapy regimens to be used and both lymph node-positive and lymph node-negative participants were eligible for enrollment. The primary efficacy endpoint of the APHINITY study is iDFS, which is the time a patient lives without return of invasive breast cancer at any site or death from any cause after adjuvant treatment. Secondary endpoints include cardiac and overall safety, overall survival, disease-free survival and health-related quality of life.

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, dual blockade of HER signaling pathways, thus preventing tumor cell growth and survival.

Perjeta Indication Statement

Perjeta is approved for use prior to surgery in combination with Herceptin and docetaxel chemotherapy in people with HER2-positive, locally advanced, inflammatory, or early stage (tumor is greater than two centimeters in diameter or node-positive) breast cancer. Perjeta should be used as part of a complete treatment regimen for early stage breast cancer. This use of Perjeta is based on an improvement in the percentage of patients whose cancer shrinks or disappears after treatment. Currently, no data have shown whether or not treatment with Perjeta prior to surgery improves survival.

  • The safety of Perjeta in combination with doxorubicin-containing regimens has not been established.
  • The safety of Perjeta administered for greater than six cycles for early stage breast cancer has not been established.

Important Safety Information

Side effects with Perjeta

  • Not all people have serious side effects; however, side effects with Perjeta therapy are common. It is important for a patient to know what side effects may happen and what symptoms a patient should watch for.
  • A patient’s doctor may stop treatment if serious side effects happen. A patient should be sure to contact their healthcare team right away if they have questions or are worried about any side effects.

Most serious side effects

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.
  • Based on test results, a patient’s doctor may hold or discontinue treatment with 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 seven months after a patient’s last dose of Perjeta. If a patient is a mother who is breastfeeding, the patient should talk with her doctor about either stopping breastfeeding or stopping Perjeta.
  • If a patient thinks she may be pregnant, the patient should contact her healthcare provider immediately.
  • If a patient is exposed to Perjeta during pregnancy, or becomes pregnant while receiving Perjeta or within seven months following the last dose of Perjeta in combination with Herceptin, the patient is encouraged to enroll in the MotHER Pregnancy Registry by contacting (800) 690-6720 or visiting http://www.motherpregnancyregistry.com , and to report Perjeta exposure to Genentech at (888) 835-2555.

Other possible serious side effects

  • Perjeta should not be used in patients who are allergic to pertuzumab or to any of the ingredients in 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 were feeling tired, abnormal or altered taste, allergic reactions, muscle pain and vomiting. The most common infusion-related reactions when receiving Perjeta alone were fever, chills, feeling tired, headache, weakness, allergic reactions 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.

Knowing if Perjeta is right for the patient

Perjeta has only been shown to work in people with HER2-positive breast cancer. A patient 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 as part of an early breast cancer regimen before surgery are:

  • Hair loss
  • Diarrhea
  • Nausea
  • Low levels of white blood cells with or without a fever

The most common side effects of Perjeta when given with Herceptin and docetaxel following three cycles of epirubicin, cyclophosphamide and fluorouracil as part of an early breast cancer regimen before surgery are:

  • Feeling tired
  • Hair loss
  • Diarrhea
  • Nausea
  • Vomiting
  • Low levels of white blood cells with or without a fever

The most common side effects of Perjeta when given with Herceptin, docetaxel and carboplatin as part of an early breast cancer regimen before surgery are:

  • Feeling tired
  • Hair loss
  • Diarrhea
  • Nausea
  • Vomiting
  • Low levels of white blood cells with or without a fever
  • Low platelet count
  • Low levels of red blood cells

Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.

Please see the full Prescribing Information for additional Important Safety Information, including most serious side effects, at http://www.perjeta.com.

Herceptin Indication Statements
Early 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.

Important Safety Information

Possible serious side effects with Herceptin

Not all people have serious side effects, but side effects with Herceptin therapy are common.

Although some people may have a life-threatening side effect, most do not.

A patient’s doctor will stop treatment if any serious side effects occur.

Herceptin is not for everyone. A patient should be sure to contact their doctor if they are experiencing any of the following:

HEART PROBLEMS

These include heart problems—such as congestive heart failure or reduced heart function—with or without symptoms. The risk for and seriousness of these heart problems were highest in people who received both Herceptin and a certain type of chemotherapy (anthracycline). In a study of adjuvant (early) breast cancer, one patient died of significantly weakened heart muscle. A patient’s doctor will check for signs of heart problems before, during, and after treatment with Herceptin.

INFUSION REACTIONS, including:

  • Fever and chills
  • Feeling sick to your stomach (nausea)
  • Throwing up (vomiting)
  • Pain (in some cases at tumor sites)
  • Headache
  • Dizziness
  • Shortness of breath

These signs usually happen within 24 hours after receiving Herceptin.

A patient should be sure to contact their doctor if they:

Are a woman who could become pregnant, or may be pregnant

Herceptin may result in the death of unborn baby and birth defects. Birth control should be used while receiving Herceptin and after a patient's last dose of Herceptin. If a patient is exposed to Herceptin during pregnancy or within seven months of becoming pregnant, the patient is encouraged to enroll in the MotHER Pregnancy Registry by contacting (800) 690-6720 or visiting http://www.motherpregnancyregistry.com and to report Herceptin exposure to Genentech at (888) 835-2555.

Have any signs of SEVERE LUNG PROBLEMS, including:

  • Severe shortness of breath
  • Fluid in or around the lungs
  • Weakening of the valve between the heart and the lungs
  • Not enough oxygen in the body
  • Swelling of the lungs
  • Scarring of the lungs

A patient’s doctor may check for signs of severe lung problems when he or she examines the patient.

Have LOW WHITE BLOOD CELL COUNTS

Low white blood cell counts can be life threatening. Low white blood cell counts were seen more often in patients receiving Herceptin plus chemotherapy than in patients receiving chemotherapy alone.

A patient’s doctor may check for signs of low white blood cell counts when he or she examines the patient.

Other important information

Before taking Herceptin, a patient must have a HER2 test to determine if their cancer is HER2-positive. This is because the benefit of treatment with Herceptin has been shown only in patients whose tumors are HER2-positive.

Side effects seen most often with Herceptin

Some patients receiving Herceptin for breast cancer had the following side effects:

  • Fever
  • Feeling sick to your stomach (nausea)
  • Throwing up (vomiting)
  • Infusion reactions
  • Diarrhea
  • Infections
  • Increased cough
  • Headache
  • Feeling tired
  • Shortness of breath
  • Rash
  • Low white and red blood cell counts
  • Muscle pain

A patient should contact their doctor immediately if they have any of the side effects listed above.

Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.

Please see the full Prescribing Information, including Boxed WARNINGS and additional Important Safety Information, 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 255,180 people in the United States will be diagnosed with breast cancer, and 41,070 will die from the disease in 2017. In HER2-positive breast cancer, increased quantities of the Human Epidermal growth factor Receptor 2 (HER2) are present on the surface of tumor cells. This is known as “HER2 positivity” and affects approximately 15-20 percent of people with breast cancer. HER2-positive cancer is a particularly aggressive form of breast cancer.

About Genentech in HER2-positive Breast Cancer

Genentech has spent more than 30 years studying the role of HER2 in cancer, and Perjeta is 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 Access Solutions
Access Solutions is part of Genentech’s commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process, and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine. To date, the team has helped more than 1.5 million patients access the medicines they need. Please contact Access Solutions (866) 4ACCESS/(866) 422-2377 or visit http://www.Genentech-Access.com for more information.

About Genentech
Founded 40 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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