Rafael Caparica1, Marco Bruzzone2, Francesca Poggio3, Marcello Ceppi2, Evandro de Azambuja1, Matteo Lambertini4. 1. Department of Medical Oncology, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Boulevard de Waterloo 121, 1000, Brussels, Belgium. 2. Clinical Epidemiology Unit, Ospedale Policlinico San Martino, Genova, Italy. 3. Department of Medical Oncology, U.O. Oncologia Medica 2, Ospedale Policlinico San Martino, University of Genova, Genova, Italy. 4. Department of Medical Oncology, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Boulevard de Waterloo 121, 1000, Brussels, Belgium. matteo.lambertini85@gmail.com.
Abstract
PURPOSE: Standard adjuvant chemotherapy for HER2-negative breast cancer consists generally in an anthracycline and taxane-based regimen (A+T). The TC (docetaxel and cyclophosphamide) regimen arises as a potential alternative, although individual randomized controlled trials (RCTs) could not demonstrate the non-inferiority of TC over A+T. This is a systematic review and meta-analysis of RCTs comparing 6 cycles of TC versus sequential A+T in the adjuvant treatment of HER2-negative breast cancer. METHODS: A systematic literature search was performed to identify RCTs comparing TC versus A+T. Disease-free survival (DFS) and overall survival (OS) were assessed. Subgroup analyses of DFS according to hormone receptor status, lymph node involvement, and menopausal status were performed. Hazard ratios (HRs) and 95% confidence intervals (CI) for DFS and OS were extracted from each trial, and a pooled analysis was conducted using the random-effect model. The Higgins' I-Squared Test was used to quantify heterogeneity. RESULTS: Seven RCTs were included (12,741 patients). Overall, no difference was observed between TC and A+T in DFS (HR 1.08, 95% CI 0.96-1.20) and OS (HR 1.05; 95% CI 0.90-1.22). A trend favoring A+T was observed in hormone receptor-negative (HR 1.12, 95% CI 0.93-1.34) and N2 patients (HR 1.25; 95% CI 0.82-1.90). Emesis/vomiting, mucositis, thrombocytopenia and sensory neuropathy were significantly more frequent with A+T. CONCLUSION: As adjuvant treatment of HER2-negative breast cancer, sequential A+T regimen was associated with increased risk of toxicities and no clear survival benefit as compared to 6 cycles of TC. Higher-risk patients may benefit the most from A+T, whilst TC may be an efficacious and less toxic alternative for lower-risk patients.
PURPOSE: Standard adjuvant chemotherapy for HER2-negative breast cancer consists generally in an anthracycline and taxane-based regimen (A+T). The TC (docetaxel and cyclophosphamide) regimen arises as a potential alternative, although individual randomized controlled trials (RCTs) could not demonstrate the non-inferiority of TC over A+T. This is a systematic review and meta-analysis of RCTs comparing 6 cycles of TC versus sequential A+T in the adjuvant treatment of HER2-negative breast cancer. METHODS: A systematic literature search was performed to identify RCTs comparing TC versus A+T. Disease-free survival (DFS) and overall survival (OS) were assessed. Subgroup analyses of DFS according to hormone receptor status, lymph node involvement, and menopausal status were performed. Hazard ratios (HRs) and 95% confidence intervals (CI) for DFS and OS were extracted from each trial, and a pooled analysis was conducted using the random-effect model. The Higgins' I-Squared Test was used to quantify heterogeneity. RESULTS: Seven RCTs were included (12,741 patients). Overall, no difference was observed between TC and A+T in DFS (HR 1.08, 95% CI 0.96-1.20) and OS (HR 1.05; 95% CI 0.90-1.22). A trend favoring A+T was observed in hormone receptor-negative (HR 1.12, 95% CI 0.93-1.34) and N2 patients (HR 1.25; 95% CI 0.82-1.90). Emesis/vomiting, mucositis, thrombocytopenia and sensory neuropathy were significantly more frequent with A+T. CONCLUSION: As adjuvant treatment of HER2-negative breast cancer, sequential A+T regimen was associated with increased risk of toxicities and no clear survival benefit as compared to 6 cycles of TC. Higher-risk patients may benefit the most from A+T, whilst TC may be an efficacious and less toxic alternative for lower-risk patients.
Entities:
Keywords:
Adjuvant chemotherapy; Anthracyclines; Breast cancer; Taxanes
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