Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2
- Study type
- Clinical trial
- Design
- Randomised trial comparing standard chemotherapy alone with standard chemotherapy plus trastuzumab
- Sample size
- 469 patients
- Source
- N Engl J Med · 2001
In plain words
In about a quarter to a third of breast cancers, there is too much of a protein called HER2, which makes the tumour more aggressive. In this study, adding the drug trastuzumab (a targeted antibody against HER2) to chemotherapy in women with metastatic breast cancer made the disease grow later, made it respond to treatment more often, and helped patients live longer. The most important side effect of this treatment was damage to heart function, which was more common in combination with anthracycline drugs but usually improved with standard medical treatment. Heart monitoring and treatment decisions should be made with your treating doctor.
Key results
Treatment arms and regimens
Patients without prior adjuvant anthracycline: doxorubicin (or epirubicin in 36 women) and cyclophosphamide alone (138 women). Patients with prior adjuvant anthracycline: paclitaxel alone (96 women).
Doses: AC = doxorubicin 60 mg/m² or epirubicin 75 mg/m² + cyclophosphamide 600 mg/m² every 21 days for 6 cycles; paclitaxel 175 mg/m² over 3 hours every 21 days for at least 6 cycles.
Patients without prior adjuvant anthracycline: doxorubicin (or epirubicin) and cyclophosphamide plus trastuzumab (143 women). Patients with prior adjuvant anthracycline: paclitaxel plus trastuzumab (92 women).
The same chemotherapy + IV trastuzumab with a loading dose of 4 mg/kg, then 2 mg/kg weekly.
Source of the regimen details: FDA label for Herceptin (DailyMed, section 14.1, study H0648g)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Women with HER2-overexpressing metastatic breast cancer. Patients who had not previously received adjuvant (post-surgical) anthracycline therapy were treated with doxorubicin (or epirubicin in 36 women) and cyclophosphamide. Patients who had previously received adjuvant anthracycline were treated with paclitaxel.
Endpoints
The abstract does not explicitly state the primary endpoint. Reported measures included time to disease progression, objective response rate, duration of response, mortality at one year, overall survival and safety (especially cardiac adverse events).
Safety and side effects
The most important adverse event was cardiac dysfunction of New York Heart Association (NYHA) class III or IV. Its rate was 27% in the anthracycline + cyclophosphamide + trastuzumab group, 8% with anthracycline + cyclophosphamide alone, 13% with paclitaxel + trastuzumab and 1% with paclitaxel alone. This cardiotoxicity was potentially severe and in some cases life-threatening, but symptoms generally improved with standard medical management.
Clinical significance and place in guidelines
According to the abstract, adding trastuzumab to first-line chemotherapy in HER2-overexpressing metastatic breast cancer increased clinical benefit and improved survival. At the same time, the risk of cardiotoxicity was high, especially with anthracyclines, and cardiac function must be carefully monitored. Regulatory approval status and current guideline recommendations are not in the abstract and should be checked separately.
Limitations
The abstract gives no information on blinding, the primary endpoint, doses or duration of treatment, and these should be checked in the full text. The higher rate of cardiotoxicity, especially with anthracyclines, is an important limitation of this approach.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.