FDA Approves Genentech’s Kadcyla for Adjuvant Treatment of People with HER2-Positive Early Breast Cancer with Residual Invasive Disease After Neoadjuvant Treatment

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has approved Kadcyla^® (ado-trastuzumab emtansine) for adjuvant (after surgery) treatment of people with HER2-positive early breast cancer (EBC) who have residual invasive disease after neoadjuvant (before surgery) taxane and Herceptin^® (trastuzumab)-based treatment.

“This approval is a significant treatment advance for HER2-positive early breast cancer. By working closely with the FDA and participating in the Real-Time Oncology Review pilot program, we are able to make Kadcyla available for people with residual invasive disease after neoadjuvant therapy much sooner than anticipated,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “With every step forward in reducing the risk of disease recurrence, we come closer to the goal of helping each person with early breast cancer have the greatest opportunity for cure.”

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 aims to eliminate any remaining cancer cells in the body to help reduce the risk of the cancer returning.

The FDA rapidly reviewed and approved the application under the FDA’s Real-Time Oncology Review (RTOR) and Assessment Aid pilot programs, leading to an approval 12 weeks after completing the submission. Kadcyla is the first Genentech medicine approved under the RTOR pilot program, which is exploring a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. For this indication, Kadcyla was also granted Breakthrough Therapy Designation, which is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases.

This approval is based on results of the Phase III KATHERINE study showing Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival; iDFS) by 50% (HR=0.50, 95% CI 0.39-0.64, p<0.0001) compared to Herceptin as an adjuvant treatment in people with HER2-positive EBC who have residual invasive disease after neoadjuvant taxane and Herceptin-based treatment. At three years, 88.3% of people treated with Kadcyla did not have their breast cancer return compared to 77.0% treated with Herceptin, an absolute improvement of 11.3%. People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease.

The most common Grade 3 or higher side effects (>2%) with Kadcyla in the KATHERINE study were decreased platelet count and high blood pressure. The most common side effects (>25%) with Kadcyla were fatigue; nausea; increased blood levels of liver enzymes; musculoskeletal pain; bleeding; decreased platelet count; headache; numbness, tingling or pain in the hands or feet; and joint pain.

For those who qualify, Genentech offers patient assistance programs for people prescribed Kadcyla by their doctor. Please contact Genentech Access Solutions at (866) 422-2377 or visit http://www.Genentech-Access.com/Kadcyla for more information.

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 iDFS including second primary non-breast cancer, disease-free survival and overall survival.

About HER2-positive breast cancer

Breast cancer is one of the most common cancers among women worldwide. According to the American Cancer Society, approximately 271,000 people in the United States will be diagnosed with breast cancer, and more than 42,000 will die from the disease in 2019. 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% 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 early and metastatic breast cancer. In the U.S., Genentech licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

Kadcyla Indication Statements

Kadcyla is approved as an adjuvant (after surgery) treatment for HER2-positive early breast cancer when the patient has taken neoadjuvant (before surgery) treatment including a taxane and trastuzumab (Herceptin) and there is cancer remaining in the tissue removed during surgery. Patients are selected for therapy based on an FDA-approved test for Kadcyla.

Kadcyla is approved to treat HER2-positive breast cancer that has spread to other parts of the body (metastatic breast cancer) after prior treatment with trastuzumab (Herceptin) and a taxane. Prior treatment could have been for the initial treatment of breast cancer or for the treatment of cancer that had spread to other parts of the body. Patients are selected for therapy based on an FDA-approved test for Kadcyla.

Important Safety Information

Most important safety information about Kadcyla

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 more than five pounds in 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 a patient’s last dose of Kadcyla.
• If a patient thinks she may be pregnant, she should contact her healthcare provider immediately.
• If a patient is exposed to Kadcyla during pregnancy or becomes pregnant within seven months following her last dose of Kadcyla, she is encouraged to report Kadcyla exposure to Genentech by calling (888) 835-2555.
• If a male patient has a female partner that could become pregnant, birth control should be used during treatment and for four months following his last dose of Kadcyla.
• A patient should not breastfeed during treatment and for seven months after the last dose of Kadcyla.

A patient 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. Even when blood thinners are not also being taken, life-threatening bleeding may occur with Kadcyla.

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.

Most common side effects of Kadcyla

The most common side effects in people taking Kadcyla for early breast cancer are:

• Tiredness
• Nausea
• Liver problems
• Pain that affects the bones, muscles, ligaments and tendons
• Bleeding
• Low platelet count
• Headache
• Weakness, numbness, and pain in the hands and feet
• Joint pain

The most common side effects seen in people taking Kadcyla for metastatic breast cancer are:

• 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. Patients may contact Genentech by calling (888) 835-2555. Patients may contact the FDA by visiting http://www.fda.gov/medwatch or calling (800) FDA-1088.

Please click here for Kadcyla full Prescribing Information, including Most Important Safety Information, for additional Important Safety Information.

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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