AVENTURA, Florida-Herceptin (trastuzumab) has produced major objective responses in 20% to 25% of patients with previously untreated metastatic breast cancers that overexpressed the HER-2 breast cancer gene. The monoclonal antibody is approved for use as first-line therapy in combination with paclitaxel (Taxol) and as a single agent in second- and third-line therapy.
AVENTURA, FloridaHerceptin (trastuzumab) has produced major objective responses in 20% to 25% of patients with previously untreated metastatic breast cancers that overexpressed the HER-2 breast cancer gene. The monoclonal antibody is approved for use as first-line therapy in combination with paclitaxel (Taxol) and as a single agent in second- and third-line therapy.
Herceptin is active as a single agent in patients who have had no prior therapy for metastatic breast cancer, and resulted in noteworthy response rates in patients who had a history of adjuvant anthracycline therapy or bone marrow transplantation, Charles Vogel, MD, an oncologist at Aventura Hospital, Aventura, Florida, said at the San Antonio Breast Cancer Symposium.
The trial involved 112 women with metastatic breast cancers that overexpressed HER-2. The protocol excluded patients who had received prior therapy for metastatic disease, but prior adjuvant therapy was allowed.
Two-thirds of the patients had received prior adjuvant chemotherapy, and 55% had prior anthracycline therapy. Dr. Vogel said that 12% had undergone bone marrow transplantation. About half had a history of radiotherapy, and 37% had prior hormonal therapy. More than half had ER-negative tumors.
Patients were randomized to receive a 4 mg/kg Herceptin loading dose, followed by 2 mg/kg weekly, or an 8 mg/kg loading dose and 4 mg/kg weekly. Responses were assessed at 8, 12, and 24 weeks, and then every 12 weeks.
At a median follow-up of 11 months, 37 patients have died. None of the deaths occurred on study, Dr. Vogel said. All occurred secondary to metastatic breast cancer. We had no discontinuations for adverse events.
Six patients had a complete response, and 20 had a partial response, resulting in an overall response rate of 23%. An additional 8% had disease stabilization for more than 6 months. Responses were durable, with several persisting beyond 2 years. The median time to progression has been 8.4 months in responders and 10.8 months in patients who had prolonged disease stabilization.
Herceptin led to responses in 25% of patients with liver metastases, 31% of patients who overexpressed HER-2 at the 3-plus level, 25% of patients who had a history of doxorubicin treatment, and 38% of patients who had received bone marrow transplants. Because of the brief follow-up period, survival cannot yet be assessed, he said.
Toxicity was generally mild and infrequent. Leukopenia occurred in 1% of patients, thrombocytopenia in none, anemia in 3% (2% severe), stomatitis in 1%, and alopecia in 4% (1% severe).
The most common adverse events were asthenia, nausea/vomiting, fever, chills, rash, headache, and diarrhea. These adverse events were almost certainly due to Herceptin, but they were generally mild and easily managed, Dr. Vogel said. There were more adverse events in the 4 mg/kg patient group. Given that there is more toxicity with the 4 mg/kg dose, and that response rates were similar with both doses, the recommended dose of 2 mg/kg should be used, he said.
Of the three cases of cardiac dysfunction, one was secondary to pericardial tamponade in a patient with a history of pericardial malignant effusion. The others involved elderly patients with a history of heart disease.