Efficacy of taxanes as adjuvant treatment of breast cancer: a review and meta-analysis of randomised clinical trials

Abstract

To evaluate the magnitude of benefit obtained by taxanes as adjuvant treatment of breast cancer and to assess the best method for their administration. We performed a systematic search of phase III randomised clinical trials that included patients with non-metastatic breast cancer in whom comparisons were chemotherapy (CT) containing a taxane (docetaxel or paclitaxel) vs. CT without taxanes (first-generation trials), or CT with taxane in both treatment arms (second-generation trials), administered after surgery. The parameters of efficacy evaluated were disease-free survival (DFS) and overall survival (OS). The data obtained in the first-generation trials (number of relapses and deaths) were submitted to a meta-analysis. The odds ratio (OR) combined with DerSimonian and Laird (OR DL) and 95% confidence interval (95% CI) were calculated. Further, an analysis was performed of those trials that included only patients with nodal involvement (N+). In both cases, the results were also analysed as a function of the taxane used, and with indirect comparisons between the two. The second-generation trials were analysed to assess the optimum method of administration. A total of 17 trials were selected for the meta-analysis (30,672 patients). The OR DL was 0.82 (95%CI: 0.76-0.88) for DFS and 0.83 (95% CI: 0.75-0.91) for OS. In N+ patients the results were 0.80 (95% CI: 0.74-0.86) and 0.79 (95% CI: 0.69-0.89), respectively. Docetaxel and paclitaxel significantly increased the DFS and OS. In our indirect comparison, the benefit of docetaxel on OS was significantly superior to that obtained with paclitaxel in N+ patients (OR: 0.79; 95% CI: 0.63-0.98). The administration of adjuvant CT-based taxanes reduces the risk of relapse and death. This reduction is superior in clinical trials that included only N+ patients. With the available evidence, it would appear that the best method of administering paclitaxel is weekly and for docetaxel tri-weekly.