Herceptin Chemotherapy Combination Improves Survival in Breast Cancer
Herceptin in combination with chemotherapy has previously shown to improve survival in patients with metastatic breast cancer. Now the results from two large randomized clinical trials for patients with HER-2 positive invasive breast cancer show that patients with early stage breast cancer also get survival benefit from this combination. Those patients with early-stage breast cancer who received Herceptin (trastuzumab) in combination with chemotherapy had a significant decrease in risk for breast cancer recurrence compared with patients who received the same chemotherapy without trastuzumab.
Trastuzumab (Herceptin) is a monoclonal antibody that blocks a growth promoting protein known as HER2/neu. This protein is normally present in small amounts in normal breast tissue and most breast cancer cells. In about 20% of the patients with breast cancer, the amount of this Her2/neu protein is increased to a much greater level. Patients who have higher levels of this protein are called Her2/neu positive and tend to have more aggressive breast cancers. Herceptin is capable of blocking the growth stimulating effect caused by the Her2/neu protein. Herceptin may also be capable of stimulating the immune system to set up a more efficient attack on the abnormally growing cancer cells.
Patients are considered to be are considered "HER-2 positive" if their cancer cells makes excess copies of HER-2 receptors, which is found on the surface of cancer cells. Trastuzumab slows or stops the growth of these cells, and it is only used to treat cancers that overexpress the HER-2 protein. About 20 percent of breast cancers overexpress HER-2. These tumors tend to grow faster and are generally more likely to recur than tumors that do not overproduce HER-2.
The clinical trials were sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the North Central Cancer Treatment Group (NCCTG), in collaboration with the Cancer and Leukemia Group B, the Eastern Cooperative Oncology Group, and the Southwest Oncology Group. Genentech, Inc., South San Francisco, Calif., which manufactures trastuzumab, provided the drug for the trials under the Cooperative Research and Development Agreement (CRADA) with NCI for the clinical development of trastuzumab.
The Data Monitoring Committees overseeing the combined analysis of these trials (known as NSABP-B-31 and NCCTG-N9831) recommended that the results of a recent combined interim analysis be made public because the studies had met their primary endpoints of increasing disease-free survival (the amount of time patients live without return of the cancer) in patients receiving trastuzumab in combination with chemotherapy. The improvement in overall survival also was statistically significant for women receiving a combination of chemotherapy and trastuzumab.
Patients in the clinical trials who received trastuzumab in combination with standard combination chemotherapy had a 52 percent decrease in disease recurrence compared to patients treated with chemotherapy alone. This difference is highly statistically significant. "This is a major advance for many thousands of women with breast cancer," said NCI Director Andrew C. von Eschenbach, M.D. "These results are one more example that we are at a major turning point in the use of targeted therapies to eliminate suffering and death from cancer," he added.
The leaders of the studies underscored the significance of these results and cited the collaborative efforts involved. "These findings confirm that we now have a very potent weapon against the recurrence of cancer cells that overexpress HER-2," said Edith A. Perez, M.D., who chaired the NCCTG trial and is a medical oncologist at the Mayo Clinic in Jacksonville, Fla. "We gratefully acknowledge the contribution of our co-investigators and, most importantly, our courageous patients in helping to achieve these unprecedented results."
Edward Romond, M.D., study chair for the NSABP and professor of oncology at the University of Kentucky, in Lexington, Ky., noted, "For women with this type of aggressive breast cancer, the addition of trastuzumab to chemotherapy appears to virtually reverse prognosis from unfavorable to good."
"These are truly life-saving results in a major disease," said JoAnne Zujewski, M.D., who oversees breast cancer trials for NCI's Cancer Therapy Evaluation Program. More detailed results from these studies will be presented at the American Society of Clinical Oncology (ASCO) annual meeting on May 16, 2005, in Orlando, Fla.
Information from over 3,300 patients enrolled in these studies was used for this analysis. Patients with operable breast cancer whose tumors over-expressed HER-2 were enrolled in these studies between February 2000 and April 2005. Patients were randomized to receive chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel, or doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab. Most patients had lymph node-positive breast cancer, or breast cancer that had spread to the lymph nodes, with only a minority having lymph node-negative disease. The limited information in the node-negative group did not allow for a separate analysis of this group.
Chemotherapy of the type given in these studies has a risk of congestive heart failure (failure of the pumping action of the heart) of less than 1 percent. In these studies, the likelihood of congestive heart failure in women receiving the combination of chemotherapy and trastuzumab was increased by 3 percent to 4 percent. Patients in these studies will continue to be followed for any additional side effects. Additional safety data will be presented at ASCO.
Trastuzumab is an example of a "targeted" therapy -- an agent that is directed against a specific change in the cancer cell. Trastuzumab was approved for the treatment of advanced breast cancer in 1998.
Reserchers from MD Anderson Cancer Center in Houston have recently shown that herceptin in combination with chemotherapy is very effective in the preoperative setting of breast cancer. You can find the link to this article below.
New options in Her2 positive breast cancer patients