ASCOUpdated results of a phase III trial show that the addition of the anti-HER2/neu monoclonal antibody (MoAb) Herceptin (trastuzumab) to chemotherapy improves survival in patients with metastatic breast cancer, compared with chemotherapy alone.
Herceptin plus either AC (Adriamycin and cyclophosphamide(Drug information on cyclophosphamide)) or paclitaxel(Drug information on paclitaxel) (Taxol) reduced the relative risk of death by about one-quarter and extended median survival time by the same amount, Larry Norton, md, said at ASCO.
Dr. Norton, chief of medical oncology and director of the Lauder Breast Center at Memorial Sloan-Kettering Cancer Center, said that this result is particularly noteworthy given that about two-thirds of patients randomized to chemotherapy alone subsequently received Herceptin when their disease progressed.
The 469 patients with HER2-overex-pressing metastatic breast cancer enrolled in the trial were divided into two strata. Patients who had not received prior adjuvant chemotherapy (n = 281) were randomized to doxorubicin(Drug information on doxorubicin) (or epirubicin(Drug information on epirubicin)) and cyclophosphamide with or without Herceptin, whereas those who had been previously exposed to adjuvant chemotherapy (n = 188) were randomized to paclitaxel with or without the MoAb.
Preliminary results of the trial had shown significant improvements in time to progression, response rate and duration, and 1-year survival in patients treated with combination therapy, albeit at the cost of increased cardiotoxicity. The updated results, obtained after a median follow-up of 29 months, showed that Herceptin combined with either chemotherapy regimen decreased the relative risk of death by 24% and increased median survival time from 20.3 to 25.4 months.
This Changes Everything
With these results, Herceptin joins a very short list of agents that have proven, in a randomized trial, to improve overall survival for metastatic breast cancer, George Sledge, Jr., MD, of Indiana University, said in his discussion of the trial. He noted that this changes everything. Testing for HER2 and use of Herceptin in HER2-positive patients should be considered part of standard care for patients with metastatic breast cancer, he said.
Nevertheless, further study is warranted to address many unresolved issues surrounding the use of Herceptin in breast cancer. One of the most important of these, according to both Dr. Sledge and Dr. Norton, is integration of the MoAb into the adjuvant setting.
Further study also is needed, Dr. Norton said, to compare Herceptin plus weekly paclitaxel with Herceptin plus the more traditional, every-3-week schedule of the taxane.
A Phase II Trial
Weekly paclitaxel plus Herceptin showed favorable results in another trial presented at ASCO. In this phase II cooperative study conducted at Memorial Sloan-Kettering and M.D. Anderson, Herceptin plus weekly paclitaxel showed activity in patients with metastatic breast cancer with toxicity similar to that seen in previous studies of paclitaxel alone.
As reported by Monica Fornier, MD, of Sloan-Kettering, only 1 of the 63 patients with HER2-positive or HER2-negative metastatic breast cancer treated with weekly paclitaxel and Herceptin suffered a cardiac event. This individual had previously received a cumulative doxorubicin dose of 615 mg/m².
Overall, left ventricular ejection fraction and cardiac function were preserved throughout the 10 months of treatment, Dr. Fornier noted. Peripheral neuropathy was the most common toxicity, but was mostly moderate in severity, and febrile neutropenia was infrequent.
Herceptin plus weekly paclitaxel produced responses in 62% of patients with HER2-positive disease and 44% of those with HER2-negative cancers, for an overall response rate of 52%.