Researchers from the University of Texas M. D. Anderson Cancer Center have found that a combination treatment of trastuzumab (Herceptin) and docetaxel (Taxotere) appears to be more effective than either treatment alone for women with metastatic breast cancer that overexpresses the HER-2 protein.
Furthermore, they appear to have developed a new blood test that may someday be able to predict how these women will respond to trastuzumab monoclonal antibody therapy.
Trastuzumab is a monoclonal antibody directed against the HER-2 protein, which is overexpressed in about 20 to 30 percent of invasive breast cancers. According to the researchers, when used alone in breast cancer patients who overexpress the HER-2 protein, trastuzumab produces a response rate in patients that ranges from 12 percent to 40 percent.
Docetaxel, a chemotherapy drug, is considered one of the most active agents when used alone in patients with metastatic breast cancer.
Writing in the Journal of Clinical Oncology, Dr. Francisco Esteva and colleagues reported that trastuzumab combined with docetaxel (Taxotere) is safe and effective in treating patients with HER-2 overexpressing metastatic breast cancer.
Of the study's 30 patients with metastatic breast cancer who also tested positive for the HER-2 protein, the overall response rate from combination treatment with trastuzumab and docetaxel was 63 percent. When patients with minor response and stable disease were considered, 83 percent of patients had some clinical benefit from the combined weekly regimen. None of the patients had a complete response. The combination appears to be less toxic than other chemotherapies used alone or in combination with trastuzumab, said the researchers.
"For some time, there have been preliminary data showing the effectiveness of trastuzumab and docetaxel, but this is the first time a full report has been published in a peer-reviewed journal," said Esteva. "While this is very good news for patients who are HER-2 positive, what is also exciting is the secondary finding of a possible new method for predicting response to trastuzumab-based therapy."
The method used in the study was a blood test that can determine the extracellular domain (ECD) of the HER-2 protein. According to Esteva, the HER-2 ECD is shed into the blood circulation and can be elevated in patients with metastatic breast cancer.
In their study, the assay measuring HER-2 ECD during treatment showed a significant correlation with a patient's response to treatment and predicted response more accurately than other assays currently in use. In patients with elevated serum HER-2 ECD at the beginning of treatment, 76 percent showed an overall response rate to trastuzumab and docetaxel treatment compared to 33 percent in patients with low HER-2 ECD concentrations at baseline.
Using other HER-2 testing methods, 63 percent of patients testing positive for HER-2 using the immunohistochemistry assay (IHC) showed a response while 67 percent of patients testing positive using the fluorescence in situ hybridization (FISH) showed response. FISH is currently considered the best predictor of response to trastuzumab monoclonal antibody therapy.
"We have much to do in this area, but if we can find a real-time predictor for how patients will respond to HER-2 targeted therapy, we can plan treatment even better," said Esteva.
SOURCES:
Journal of Clinical Oncology, April 1, 2002; 20(7):1800-1808
University of Texas M.D. Anderson Cancer Center (http://www.mdanderson.org)
