P5-18-06: Taxanes and Cyclophosphamide Are Equally Effective in Breast Cancer: A Meta-Analysis of Ten Phase III Trials in Early and Advanced Disease.

Abstract

Abstract Background Overall taxanes did not improve survival in metastatic breast cancer trials (n=10 trials), whereas they do so in (neo-)adjuvant breast cancer trials (n=28 trials). We also noticed that in a substantial number of ‘negative’ metastatic trials, taxane-regimens were used without cyclophosphamide. To further explore this, we compared the outcome of studies in early and advanced breast cancer with a similar design, that is all studies substituting taxanes for cyclophosphamide. Methods We identified 10 phase III taxane-based chemotherapy trials in early and advanced disease, in which taxanes were used instead of cyclophosphamide. They all compared a regimen of an anthracycline combined with a taxane versus an anthracycline combined with cyclophosphamide, i.e., AT versus AC. A pooled analysis was performed using the Review Manager software (RevMan 5) provided by the Cochrane Collaboration. Results In total, 5 studies in advanced disease, 2 studies in neoadjuvant, and 3 studies in adjuvant disease setting were included and analyzed for their primary endpoint. In metastatic breast cancer studies, the hazard ratio of overall survival was 1.03 (95% CI 0.92 to 1.15) for taxanes as compared to cyclophosphamide. Also, studies on early breast cancer with a similar design showed no improvement for taxanes, resulting in an odds ratio for pCR of 0.91 (95% CI 0.57 to 1.43) in the neo-adjuvant setting and a hazard ratio for 5-year disease-free survival of 0.96 (95% CI 0.84 to 1.09) in the adjuvant setting. Conclusion Re-assessment of studies of drugs both assessed in metastatic and early breast cancer provides a new tool for improved understanding. This meta-analysis shows that cyclophosphamide in breast cancer patients is equally effective as taxanes, and thus should be considered of pivotal importance in the treatment of metastatic and early breast cancer. Full appreciation of its relevance will prevent replacement of cyclophosphamide in future trials or in daily practice. Funding: Netherlands Organization for Health Research and Development (ZonMw 80–82500-98-10901) Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-06.