-- Phase II Study Evaluating a Novel Targeted Combination Regimen Showed Promising Results in the Neoadjuvant (Pre-surgery) Setting --
SAN ANTONIO, Texas--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced results from the NEOSPHERE trial, a Phase II neoadjuvant study evaluating the effect of a novel combination regimen of pertuzumab and Herceptin® (trastuzumab) plus chemotherapy (docetaxel) in women with early-stage, HER2-positive breast cancer. The data, presented at the CTRC-AACR San Antonio Breast Cancer Symposium (SABCS), showed that the two antibodies plus docetaxel, given in the neoadjuvant setting prior to surgery, significantly improved the rate of complete tumor disappearance (pathological complete response rate, pCR, of 45.8 percent) in the breast by more than half compared to Herceptin plus docetaxel (pCR of 29.0 percent), p=0.014.
“The findings of the NEOSPHERE study suggested that this new approach was effective for early HER2-positive breast cancer,” said Professor Luca Gianni, Principal Investigator of the study and Director of Medical Oncology at the National Cancer Institute in Milan, Italy. “The combination of pertuzumab and Herceptin plus chemotherapy had a substantial effect on HER2-positive breast cancer tumors after just four cycles (12 weeks) of neoadjuvant use.”
The combination of pertuzumab and Herceptin plus docetaxel was not associated with a significant increase in side effects or cardiac risk compared to Herceptin and chemotherapy. The most common severe (Grade 3 or higher) side effects were neutropenia (low white blood cell count, 44.9 percent), fever that was associated with neutropenia (8.4 percent) and diarrhea (5.6 percent).
“We are committed to developing new medicines that make a difference for people living with cancer and to advancing personalized treatments,” said Hal Barron, M.D., executive vice president, Product Development and chief medical officer. “The clinical data presented today (at SABCS) add to the body of evidence that this novel targeted regimen plus chemotherapy may improve outcomes in women with HER2-positive breast cancer.”
Based on these findings, Genentech/Roche plans to initiate a Phase III study in HER2-positive early (adjuvant) breast cancer in 2011. In addition, CLEOPATRA, a Phase III study evaluating the efficacy and safety profile of pertuzumab and Herceptin plus chemotherapy as a first-line regimen in people with HER2-positive metastatic breast cancer, completed enrollment in Q2 2010 and results are expected by the end of 2011.
About the NEOSPHERE Trial
The NEOSPHERE study (Neoadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation) is a randomized, multicenter, international Phase II study that was conducted at 78 centers worldwide (except the United States) in 417 women with newly diagnosed HER2-positive early, inflammatory or locally advanced breast cancer who had never received Herceptin. Prior to surgery (neoadjuvant treatment) these women were randomized to four study arms. The primary endpoint was complete tumor disappearance at time of surgery (pathological complete response, pCR), and the results were:
- pCR of 29.0 percent for Herceptin and docetaxel
- pCR of 45.8 percent for Herceptin, pertuzumab and docetaxel
- pCR of 16.8 percent for Herceptin and pertuzumab
- pCR of 24.0 percent for pertuzumab and docetaxel
Secondary endpoints include clinical response, time to clinical response, safety profile, disease-free survival, breast-conserving surgery rate and biomarker assessment.
About Breast Cancer
According to the American Cancer Society, breast cancer is the second most commonly diagnosed cancer and the second leading cause of cancer deaths among women in the U.S. In 2010, more than 209,000 Americans will be diagnosed and more than 40,000 will die from the disease. There are approximately 2.5 million breast cancer survivors in the U.S. In HER2-positive breast cancer, increased quantities of the HER2 receptor are present on the surface of the tumor cells. This is known as “HER2 positivity” and affects approximately 25 percent of women with breast cancer.
Pertuzumab is a monoclonal antibody being studied in early-stage and metastatic HER2-positive breast cancer. It is a novel targeted medicine called a “HER2 dimerization inhibitor” (HDI). HER dimerization (pairing) is believed to play an important role in the growth and formation of several different cancer types. Pertuzumab is the first investigational medicine designed to specifically prevent the HER2 receptor from pairing with other HER receptors (EGFR/HER1, HER2, HER3, HER4). In cancer cells, interfering with HER2’s ability to collaborate with other HER family receptors blocks cell signaling, which may ultimately inhibit cancer cell growth or lead to the death of the cancer cell. The modes of action of pertuzumab and Herceptin are believed to complement each other. Both bind to the HER2 receptor but in different regions. By doing so it is hypothesized that the two antibodies in combination may provide a more comprehensive blockade of the HER signaling pathways than either agent alone.
Herceptin is a targeted medicine (not a chemotherapy) designed to specifically block the HER2 protein on the surface of some cancer cells. Based on preclinical studies, Herceptin may 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 cancer cells.
Adjuvant Breast Cancer:
Herceptin is approved for the treatment of early-stage breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2-positive) and has spread into the lymph nodes, or is HER2-positive and has not spread into the lymph nodes, but has 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 estrogen receptor/progesterone receptor (ER/PR)-negative with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.
Metastatic Breast Cancer:
Herceptin has two approved uses in metastatic breast cancer:
- Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first-line treatment of HER2-positive metastatic breast cancer
- Herceptin alone is approved for the treatment of HER2-positive breast cancer in patients who have received one or more chemotherapy courses for metastatic disease
Metastatic Gastric Cancer:
Herceptin is approved in combination with the chemotherapy drugs cisplatin, and either capecitabine or 5-fluorouracil, for metastatic HER2-positive stomach cancer or cancer of the gastroesophageal junction, in men and women who have not received prior medicines for their 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) breast cancer trial from significantly weakened heart muscle. The risk and seriousness of these heart problems were highest in people 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 MUGA scan. Some early 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), 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 or stomach 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, fatigue, shortness of breath, rash, low white and red blood cells, and muscle pain.
The most common side effects associated with Herceptin in patients with stomach cancer are low white blood cell counts, diarrhea, fatigue, low red blood cell counts, inflammation of the lining of the mouth, weight loss, upper respiratory tract infections, fever, low platelet counts, swelling of mucus membranes, swelling of the nose and throat, and a change in taste.
Because everyone is different, it is not possible to predict what side effects any one person will have. Patients with questions or concerns about side effects should talk to their doctor.
Patients should read the Herceptin Full Prescribing Information including Boxed WARNINGS, at http://www.herceptin.com.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines for 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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