Anthracycline and taxane-based (A+T) chemotherapy (CT) is the current standard adjuvant CT for HER2-negative BC patients. However, anthracyclines can be associated with important short and long-term toxicities (e.g. cardiotoxicity and leukemias). After a phase 3 trial demonstrated that docetaxel+cyclophosphamide (TC) was more effective than doxorubicin + cyclophosphamide (AC), the use of TC has increased. Nevertheless, RCTs could not demonstrate that TC is non-inferior to the standard A+T. This is a systematic review and meta-analysis of RCTs comparing A+T versus TC as adjuvant CT in HER2-negative BC patients.
A literature search using PubMed, EMBASE, Cochrane, ASCO, ESMO and SABCS websites was performed up to March 30, 2018, to identify RCTs comparing TC vs A+T as adjuvant CT in HER2-negative BC patients. Disease-free survival (DFS) and overall survival (OS) were assessed. A subgroup analysis of DFS in hormone receptor positive (HR+) and negative (HR-) disease was also performed. Hazard ratios (HR) and 95% confidence intervals (CI) for DFS 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.
A total of 8 RCTs that randomized 12,741 early BC patients were included. Five RCTs were published as pooled results: ABC trials comprised 3 RCTs, and PlanB + Success-C comprised 2 RCTs. The comparison of TC versus A+T demonstrated a non-significant benefit in favour of A+T for both DFS (HR 1.08, 95% CI 0.96 - 1.20) and OS (HR 1.05; 95%CI 0.90 – 1.22). The magnitude of the benefit of A+T was more pronounced in patients with HR- disease, (N = 1,947, HR 1.12, 95% CI 0.93 – 1.34) compared to those with HR+ disease (N = 4,867, HR 1.05, 95%CI 0.86 – 1.27).
Globally, our results showed that A+T was associated with a slight non-significant improvement in DFS and OS as compared to TC. Nevertheless, in selected patients such as those with HR+ disease, TC may be considered an alternative option to avoid the toxicities of anthracycline-based CT.
Clinical trial identification
CRD42018090962 - PROSPERO register.
Legal entity responsible for the study
Institut Jules Bordet.
Has not received any funding.
All authors have declared no conflicts of interest.