- Phase III TH3RESA study results will be presented today at the European Cancer Congress in Amsterdam
- Kadcyla nearly doubled the time that people lived without their disease worsening compared with treatment of physician’s choice
- Kadcyla is the first antibody-drug conjugate to result from Roche and Genentech’s 30 years of HER2 pathway research
SOUTH SAN FRANCISCO, CA, USA I September 28, 2013 I 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 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”
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 Study
TH3RESA 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%) |
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| 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% CI 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 |
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Table summarizing PFS results from Kadcyla arm and Herceptin-based regimens from the treatment of physician’s choice arm
| 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 difference HR=0.558 (95% CI 0.437, 0.771) p<0.0001 |
6.2 months median PFS | 3.2 months median PFS | |||
About Kadcyla
Kadcyla is an ADC being studied in HER2-positive cancers. It is the first ADC to result from Genentech’s 30 years of HER2 pathway research and the third medicine Genentech has developed for the treatment of HER2-positive breast cancer. Genentech licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.
Kadcyla Indication Statement
Kadcyla® (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.
Important Safety Information
Kadcyla is not the same medicine as trastuzumab (Herceptin).
There are possible serious side effects of Kadcyla. Patients must contact their doctor right away if they experience any of these symptoms. The patient’s doctor may do tests before starting Kadcyla and before each dose to monitor for these side effects. Kadcyla treatment may be stopped or the dose may be lowered if the patient experiences any of these side effects. Patients must contact their doctor right away if they experience any of these symptoms.
Liver Problems
- 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.
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 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.
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. The patient’s doctor will monitor the patient for infusion-related reactions.
Low Platelet Count
- Low platelet count may happen during treatment with Kadcyla. Platelets are cells in the blood that help the blood clot.
Nerve Damage
- Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, or 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, as benefit has only been shown 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
- Low platelet count
- Headache
- Liver problems
- Constipation
Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients and caregivers may also report side effects to Genentech at (888) 835-2555.
For full Prescribing Information and Boxed WARNINGS on Kadcyla, please visit http://www.kadcyla.com.
About Herceptin
Herceptin is a medicine designed to specifically block the HER2 protein on the surface of cells that overexpress the HER2 protein. 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 cells.
Adjuvant 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.
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.
Important Safety Information
Herceptin treatment can result in heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). One patient died in an adjuvant (early stage) 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, 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.
SOURCE: Genentech
