Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials
- Study type
- Meta-analysis
- Study name
- EBCTCG 2012
- Design
- Individual-patient-data meta-analysis of randomised trials
- Sample size
- About 100,000 women in 123 randomised trials
- Source
- The Lancet · 2012
In plain words
This study gathered information on about 100,000 women with early breast cancer from 123 trials and compared different chemotherapy regimens given after surgery. Some regimens, including a taxane combined with an anthracycline or anthracycline regimens with a higher total dose, reduced deaths from breast cancer by about a third on average, and this effect largely did not depend on age or tumour features. The real benefit for each patient depends on her risk without chemotherapy; if that risk is low, the absolute benefit is also low. The choice of regimen should be made together with the treating doctor.
Key results
Treatment arms and regimens
Taxane-plus-anthracycline-based regimens versus the same regimen, or more, non-taxane chemotherapy. In one set of trials, four separate cycles of a taxane were added to a fixed anthracycline-based control regimen (extending treatment duration); in the other set, four extra cycles of a taxane were balanced by extra cycles of other cytotoxic drugs in the control group (roughly doubling the non-taxane dosage).
One anthracycline-based regimen versus another or versus CMF (cyclophosphamide, methotrexate and fluorouracil). The scheduled doses of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to define standard CMF, standard 4AC, CAF and CEF.
Trials comparing polychemotherapy (such as CAF, standard 4AC and standard CMF) with no chemotherapy.
Meta-analysis of multiple trials; dose and schedule varied between trials and no single dose is reported.
Source of the regimen details: Abstract of the paper (meta-analysis; no single dose)
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 early breast cancer enrolled in randomised trials comparing adjuvant chemotherapy regimens. According to the abstract, the comparisons included: taxane-plus-anthracycline regimens versus the same, or more, non-taxane chemotherapy (44,000 women); one anthracycline-based regimen versus another (7000 women) or versus CMF (18,000 women); and polychemotherapy versus no chemotherapy (32,000 women). Other inclusion criteria are not given in the abstract.
Endpoints
Breast cancer mortality rate ratios (RR) were reported using log-rank analyses. Overall mortality at 10 years was also assessed and was consistent with the differences in breast cancer mortality.
Safety and side effects
According to the abstract, differences in overall mortality at 10 years were consistent with differences in breast cancer mortality, despite toxicities from taxanes, anthracyclines and other drugs. Exact rates of grade 3 or higher adverse events are not reported in the abstract.
Clinical significance and place in guidelines
This meta-analysis shows that some taxane-plus-anthracycline regimens or anthracycline regimens with a higher cumulative dose reduce breast cancer mortality compared with older standard regimens, and it can guide the choice of adjuvant chemotherapy regimen. The absolute benefit depends on baseline risk, and according to the abstract, gene expression markers or quantitative immunohistochemistry for predicting risk and response were not available in this analysis. The status of these findings in current clinical guidelines should be checked separately.
Limitations
According to the abstract, no information was available on tumour gene expression markers or quantitative immunohistochemistry that could predict risk, chemosensitivity or both. Also, few tumours were well differentiated, and the results are limited to the characteristics of the patients selected for the trials. Other limitations should be checked in the full text.
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.