Presenting the findings at the American Society of Clinical Oncology (ASCO) meeting, Aman Buzdar, M.D., professor in the Department of Breast Medical Oncology at M. D. Anderson, reported that more than 65 percent of early stage, HER-2 positive patients experienced a complete response rate after receiving Herceptin with chemotherapy compared to 26 percent of patients with similar tumor types who received chemotherapy only.
Buzdar said that because the results were so striking, the Phase III trial was halted early after accrual of 42 of the originally planned 164 patients. After reviewing results of 42 patients and finding the overwhelming increase in complete response, Buzdar and his team stopped and revised the trial so that all M. D. Anderson patients newly diagnosed with early stage, HER-2 positive tumors receive Herceptin plus chemotherapy prior to surgery. Had the trial continued and accrued the 164 patients as planned, there was a 95 percent probability that patients receiving the Herceptin would experience similar outcome, he reported.
All the trial participants had surgery after completing chemotherapy alone or chemotherapy with Herceptin. According to Buzdar, even though most of the breast tumors either virtually disappeared or shrank dramatically with the pre-surgery chemotherapy and Herceptin treatment, the breast still had to be treated surgically.
About 25 percent to 30 percent of all breast cancer patients have tumors that are HER-2 positive, a marker that can signal a poorer prognosis due to increased risk of recurrence and decreased sensitivity to chemotherapy, said Buzdar.
Buzdar said when he and his team began the study more than two years ago, they wanted to go one step beyond previous studies that showed Herceptin plus chemotherapy could extend survival and control disease in patients with advanced or metastatic breast cancer.
"When we started this trial with early stage breast cancer patients, we had hoped to see a 20 percent improvement in complete response, but we actually found a 39 percent improvement with the addition of Herceptin," said Buzdar. "This is a significant stride in treating women with confined breast tumors which have tested positive for the HER-2 gene. In my 30-plus years of clinical research in breast cancer, I believe these are among the most striking results I have seen."
Buzdar said that because of the significant results, the trial's Data Monitoring Committee determined that the trial should be closed so that more patients could take advantage of the superior treatment of chemotherapy combined with Herceptin. Currently, all newly diagnosed patients at M. D. Anderson who have local, HER-2 positive breast disease receive the chemotherapy with Herceptin in advance of their surgery.
Patients enrolled on the study were randomized to four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin and cyclophosphamide alone or the same regimen with 24 weekly, simultaneous Herceptin treatments. Following the chemotherapy with or without the Herceptin and surgery, patients received appropriate follow-up treatment.
Buzdar reported few major side effects, including heart damage, from the trial. To offset known heart toxicities often attributed to Herceptin, patients received epirubicin as one of the three drugs in the chemotherapy regimen. Epirubicin has been shown to be less toxic to the heart than others. Fevers or neutropenia were experienced by a small percentage of patients, particularly among those on the Herceptin arm of the trial.
Buzdar said the research team would build on the data and experience gained from this trial and develop future trials that will explore results in a larger group of patients and look more closely at the effect the treatment may have on the type of surgery necessary after chemotherapy.
Additional contact information:
Laura Sussman
ASCO
Cell: 832-264-8893
Julie Penne
Cell: 281-460-1788
Abstract #520