Adjuvant chemotherapy has an indisputable value for early breast cancer. Τaxane + cyclophosphamide combination (TC) has demonstrated superiority against cyclophosphamide + anthracycline (AC) in disease-free (DFS) and overall survival (OS). However, 5 randomized clinical trials (RCTs) failed to show non-inferiority of TC compared to an anthracycline-taxane combination (TaxAC). We conducted a meta-analysis of these RCTs to better estimate the cumulative evidence for non-inferiority of TC against TaxAC, in the adjuvant setting of HER2-negative, breast cancer.
The ABC trials, the Plan B trial and a trial by the Hellenic Oncology Research Group (HORG) were meta-analyzed. The DFS was the primary endpoint. A DFS-HR of 1.18 for TC versus TaxAC, was chosen to demonstrate inferiority, as it was the most conservative measure among the included studies. Secondary endpoints were OS and toxicity profile.
Overall, 7,341 patients composed the meta-analysis population. We didn’t encounter heterogeneity between the trials (Q-test p = 0.55, I2:0%) and no publication bias was detected. Non-inferiority of TC was not established (DFS-HR=1.11, 95%CI: 0.95-1.30, p = 0.18). The combined DFS rates, according to the time points set by each study, were 89.04% versus 90.35% for TC and TaxAC respectively. Non-inferiority of TC was also not proven for the node-negative population either (HR = 1.05, 95%CI: 0.82-1.34, p = 0.71). Grade 3-4 leucopenia (OR: 1.2, 95%CI:1.068-1.348, p = 0.002) and thrombocytopenia (OR = 6.455; 95%CI:2.902-14.359, p < 0.001) prevailed in the TaxAC group, while cardiotoxicity was also increased (OR = 2.283; 95%CI:1.155-4.514, p = 0.015).
Although the TC combination was not proven to be non-inferior to TaxAC, the present analysis narrows the HR of recurrence risk of recurrence with a difference in the DFS rate of only 1,31%. Taking into account the more favorable safety profile of the TC combination, the question as to which treatment regimen should be preferred under what circumstances needs to be individualized according to patients’ characteristics and desires.
Clinical trial identification
Legal entity responsible for the study
Hellenic Academy of Oncology.
Has not received any funding.
All authors have declared no conflicts of interest.