Wednesday, Dec 5, 2018

Genentech’s Kadcyla Cut the Risk of Disease Recurring by Half Compared to Herceptin in People With HER2-Positive Early Breast Cancer With Residual Disease After Neoadjuvant Treatment

At three years, 88.3 percent of people treated with Kadcyla in the adjuvant HER2-positive early breast cancer setting did not have their breast cancer return compared to 77.0 percent treated with Herceptin, an 11.3 percent improvement

People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease

Data from the Phase III KATHERINE study will be submitted to health authorities globally, including the U.S. Food and Drug Administration and
European Medicines Agency

Results are being presented at the 2018 San Antonio Breast Cancer Symposium, featured in the press program and simultaneously published in the New England Journal of Medicine on Wednesday, December 5

South San Francisco, CA -- December 5, 2018 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced the Phase III KATHERINE study met its primary endpoint, showing Kadcyla^® (ado-trastuzumab emtansine) as a single agent significantly reduced the risk of disease recurrence or death (invasive disease-free survival; iDFS) by 50 percent (HR=0.50, 95% CI 0.39-0.64, p<0.0001) compared to Herceptin^® (trastuzumab) as an adjuvant (after surgery) treatment in people with HER2-positive early breast cancer (EBC) who have residual disease (pathological invasive residual disease in the breast and/or axillary nodes) present following neoadjuvant (before surgery) treatment. At three years, 88.3 percent of people treated with Kadcyla did not have their breast cancer return compared to 77.0 percent treated with Herceptin, an 11.3 percent improvement. Kadcyla improved iDFS irrespective of hormone receptor status, lymph node status and prior HER2-targeted treatment regimen received in the neoadjuvant setting. The safety profile of Kadcyla was consistent with that seen in previous studies, and no unexpected or new safety signals were identified.

“The KATHERINE results demonstrate a significant reduction in the risk of recurrence of HER2-positive early breast cancer in people with residual disease after neoadjuvant therapy, and we look forward to submitting these data to health authorities as soon as possible,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We come closer to the goal of helping each person with early breast cancer have the greatest opportunity for cure with every advance in reducing disease recurrence.”

The goal in treating EBC is to provide people with the best chance for a cure, which may involve treatment before and after surgery as part of a comprehensive treatment approach. While we come closer to this goal with each advance, many people still have a disease recurrence in the long-term. Neoadjuvant treatment is given before surgery with the goal of shrinking tumors and helping to improve surgical outcomes. Adjuvant treatment is given after surgery and is aimed at eliminating any remaining cancer cells in the body to help reduce the risk of the cancer returning.

These results are being presented in an oral session today at the 2018 San Antonio Breast Cancer Symposium (SABCS) at 11:00 a.m. CST (abstract GS1-10) and featured in the official SABCS press program at 7:15 a.m. These results will simultaneously be published in the New England Journal of Medicine.

About  the KATHERINE study

KATHERINE is an international, multi-center, two-arm, randomized, open-label, Phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive EBC who have pathological invasive residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy that included Herceptin and taxane-based chemotherapy. The primary endpoint of the study is iDFS, which in this study is defined as the time from randomization free from invasive breast cancer recurrence or death from any cause. Secondary endpoints include disease-free survival and overall survival.

About HER2-positive breast cancer 

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 269,000 people in the United States will be diagnosed with breast cancer, and more than 41,000 will die from the disease in 2018. Breast cancer is not one, but many diseases based on the biology of each tumor. In HER2-positive breast cancer, there is excess HER2 protein on the surface of tumor cells. Approximately 15-20 percent of breast cancers are HER2-positive based on the result of a diagnostic test.

About Kadcyla

Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells. It is designed to limit damage to healthy tissues, although it can still affect them. Kadcyla can cause serious side effects. It combines two anti-cancer agents using a stable linker: the HER2-targeting trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1. Kadcyla is the only ADC approved for the treatment of HER2-positive metastatic breast cancer. In the U.S., Genentech licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

Kadcyla Indication Statement

Kadcyla^® (ado-trastuzumab emtansine), as a single agent, is indicated for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:

• Received prior therapy for metastatic disease, or
• Developed disease recurrence during or within six months of completing adjuvant therapy.

Important Safety Information

What is the most important safety information patients should know about Kadcyla? 

Kadcyla is not the same medicine as trastuzumab (Herceptin). 

Liver problems

• Kadcyla may cause severe liver problems that can be life threatening. Symptoms of liver problems may include vomiting, nausea, eating disorder (anorexia), yellowing of the skin (jaundice), stomach pain, 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 receiving Kadcyla and for seven months after the last dose of Kadcyla.
• If a patient is exposed to Kadcyla during pregnancy, or becomes pregnant within seven months of their last dose of Kadcyla, she should contact her healthcare provider right away; she is also encouraged to enroll in the MotHER Pregnancy Registry by calling (800) 690-6720 or visiting http://www.motherpregnancyregistry.com.
• Patients are also encouraged to report exposure to Kadcyla during pregnancy, or if they become pregnant within seven months of their last dose, to Genentech by calling (888) 835-2555.
• If the patient is a mother who is breastfeeding, she should talk with her doctor about either stopping breastfeeding or stopping Kadcyla.

Patients should contact their doctor right away if they experience symptoms associated with these side effects. 

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. A 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 the blood (antiplatelet) or prevent blood clots (anticoagulation) can increase the risk of bleeding. A 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 help the blood to clot. Signs of low platelets may include easy bruising, bleeding, and prolonged bleeding from cuts. In mild cases there may not be any symptoms.

Nerve damage

• Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, 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, because benefit has been shown only 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

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 Kadcyla full Prescribing Information for additional Important Safety Information, including most serious side effects, at http://www.kadcyla.com.

Herceptin Indication Statement

Adjuvant Breast Cancer

Herceptin is approved for the treatment of early stage breast cancer that is Human Epidermal growth factorReceptor 2-positive ( 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 (doxorubicin) based therapy (a type of chemotherapy)

Patients are selected for therapy based on an FDA-approved test for Herceptin.

*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 an unborn baby or birth defects. Contraception should be used while receiving Herceptin and for seven months after a patient's last dose of Herceptin. If a patient is or becomes pregnant while receiving Herceptin or within seven months after their last dose of Herceptin, the patient should immediately 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.

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 Herceptin full Prescribing Information for additional Important Safety Information, including most serious side effects, at http://www.herceptin.com.

About Genentech in breast cancer 

Genentech has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have substantially improved outcomes for HER2-positive breast cancer. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including triple-negative and hormone receptor-positive.

About Genentech
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and 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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