Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that Kadcyla ® (ado-trastuzumab emtansine) significantly extended the time people with advanced HER2-positive breast cancer (metastatic and unresectable locally advanced/recurrent) lived without their disease worsening (progression-free survival [PFS], a co-primary endpoint) compared to people who received a treatment of their physician’s choice in an open-label Phase III study called TH3RESA. The data showed the risk of disease worsening or death was reduced by 47 percent for people who received Kadcyla (HR=0.528, p<0.0001). Data for overall survival, the other co-primary endpoint, are not yet mature. No new safety signals were observed with Kadcyla. The study enrolled people with advanced HER2-positive breast cancer who had progressed despite prior treatment with at least two HER2-targeted medicines. It randomized people to receive either treatment with Kadcyla or a treatment of their physician’s choice. Eighty percent of people treated with physician’s choice received a regimen containing Herceptin ® (trastuzumab). “The TH3RESA study is the second large Phase III study in which Kadcyla has improved the amount of time patients with an advanced form of HER2-positive breast cancer lived without their tumor growing,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “We are pleased that the data from multiple clinical trials reinforces Kadcyla’s benefit for people with this aggressive disease.” The late-breaking TH3RESA data will be presented tomorrow at the European Cancer Congress (ECC), by Dr. Hans Wildiers, University Hospital Leuven, Gasthuisberg, Belgium (Abstract #LBA15, Saturday, September 28, 2013 at 1:03 p.m. CEST). The data are also part of the official press program. In February 2013, Kadcyla was approved by the U.S. Food and Drug Administration for the treatment of people with HER2-positive metastatic breast cancer who have received prior treatment with Herceptin and a taxane chemotherapy. Kadcyla recently received a positive opinion from the European Union’s Committee for Medicinal Products for Human Use (CHMP) as a single agent for the treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received Herceptin and a taxane, separately or in combination. A European Commission decision on EU marketing approval is expected by the end of the year.
About the TH3RESA StudyTH3RESA is a Phase III, randomized, open-label study comparing Kadcyla to the physician's choice of treatment in approximately 600 people with advanced HER2-positive breast cancer (metastatic or locally recurrent unresectable) who have received at least two prior treatments including Herceptin, lapatinib and a taxane. The co-primary endpoints are investigator-assessed PFS and OS. The secondary endpoints include objective response rate and safety profile.
|Comparison||Kadcyla||Treatment of Physician’s Choice Options included chemotherapy and Herceptin (68.5%), single agent chemotherapy (16.8%), lapatinib and Herceptin (10.3%), chemotherapy and lapatinib (2.7%), hormonal therapy and Herceptin (1.6%)|
|Median PFS (Investigator Assessment)||2.9 month difference HR=0.528 (95% CI 0.422, 0.661) p<0.0001||6.2 months median PFS||3.3 months median PFS|
|Overall Survival (OS)||The OS endpoint has not yet been reached HR=0.552 (95% CI 0.369, 0.826) p=0.0034||Median OS not yet reached||14.9 months median OS|
|Objective Response Rate (ORR)||22.7% difference (95% CI16.2, 29.2) p<0.0001||31.3%||8.6%|
|Safety profile: Rate of Grade 3 or higher AEs||32.3%||43.5%|
|Most common Grade 3 or higher AEs (occurring in more than 2% of patients)||Decrease in platelets (4.7%), low red blood cell count (2.7%), decrease in a certain type of white blood cell (2.5%), increased levels of enzymes released by the liver and other organs (2.2%), fatigue (2.0%) and difficulty breathing (2.0%)||Decrease in a certain type of white blood cell (15.8%), diarrhea (4.3%), fever associated with decrease in a certain type of white blood cell (3.8%), abdominal pain (2.7%), low red blood cell count (2.7%), low white blood cell count (2.7%), increased levels of enzymes released by the liver and other organs (2.2%), fatigue (2.2%), physical weakness (2.2%), skin infection (2.2%) and blood clot in the lung|
|Comparison||Kadcyla||Subset of patients receiving Herceptin as part of the treatment of physician’s choice (80.4%)|
|Median PFS(Investigator Assessment)||3.0 month differenceHR=0.558 (95% CI 0.437, 0.771)p<0.0001||6.2 months median PFS||3.2 months median PFS|
Kadcyla Indication StatementKadcyla ® (ado-trastuzumab emtansine) is approved for the treatment of people with HER2-positive metastatic breast cancer (MBC) who have received prior treatment with Herceptin ® (trastuzumab) 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Low platelet count may happen during treatment with Kadcyla. Platelets are cells in the blood that help the blood clot.
- Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, or muscle weakness or loss of muscle function.
- 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 KadcylaThe most common side effects seen in people taking Kadcyla were:
- Pain that affects the bones, muscles, ligaments and tendons
- Low platelet count
- Liver problems
- 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).
Metastatic Breast Cancer:Herceptin has two approved uses in 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 courses for metastatic disease.
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, feeling tired, 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. Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at (888) 835-2555. 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 235,000 people in the United States will be diagnosed with breast cancer, and 40,000 will die from the disease in 2013. 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 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.