A new use of the drug Herceptin appears to offer a much more powerful treatment advantage than expected for patients with HER-2-positive breast cancer, say researchers at The University of Texas M. D. Anderson Cancer Center.
When combined with chemotherapy and used before surgery in early stage breast cancer the drug proved so beneficial - eliminating 42 percent more tumors than chemotherapy alone - that the clinical trial testing of this new treatment plan was halted early, the researchers report in the Journal of Clinical Oncology.
"This is a far better result than we had anticipated and seems to suggest that simultaneous use of chemotherapy and Herceptin offers a much more potent treatment than use of these drugs sequentially, or alone," says lead investigator Aman Buzdar, M.D., professor in the Department of Breast Medical Oncology at M. D. Anderson.
"This is the best treatment result we have seen in this patient population," Buzdar says. "It shows that we can potentially change the natural history of a disease that is associated with a high risk of recurrence and death."
He cautions, however, that although this combination of therapies seems to show better efficacy, as well as less risk of heart damage than has been seen before with Herceptin treatment, "the jury is still out on the long-term safety and outcome. As in all such studies, we will need to wait years to follow the progress of our patient participants," Buzdar says.
Details of the trial result, slated for the June issue of the journal, were posted online Feb. 28 because of interest in the study. Preliminary results of the trial were presented in June, 2004 at the annual meeting of the American Society of Clinical Oncology.
After only 34 of a planned 164 patients had completed therapy, the trial's Data Monitoring Committee stopped the clinical trial because of the obvious benefit seen in patients who received Herceptin and chemotherapy before surgery, compared to patients treated with chemotherapy alone. In that group, rates of pathological complete remission (pcr), defined as the complete disappearance of cancer in breast tissue removed during surgery, was 66.7 percent in Herceptin-treated patients, compared to 25 percent in patients who received only chemotherapy.
Of all 42 patients who had enrolled in the study, including the eight who continued to receive treatment after the study had been halted, 26 percent in the chemotherapy arm achieved pathologic complete remission, compared with 65.2 percent in patients treated with both Herceptin and chemotherapy, according to the JCO study.
If the trial had enrolled all 164 patients, statisticians calculated a 95 percent probability that the combination of Herceptin and chemotherapy would prove superior, Buzdar says.
Giving a new combination of drugs together and for a longer time
Between 25 percent and 30 percent of breast cancers are known to over-express the human epidermal growth factor receptor 2 (HER-2), a protein that fuels the growth, and thus the aggressiveness, of the cancer. Herceptin is a monoclonal antibody drug designed to block the action of these receptors, but use of the agent by itself has shown only modest benefits.
The Food and Drug Administration approved use of Herceptin in 1998 for treatment of metastatic breast cancer in combination with chemotherapy. The long term outcome of such treatment, however, has not yet been established, according to Buzdar, and several large and lengthy clinical trials are now under way to test for cancer recurrence and survival after use of Herceptin with chemotherapy.