Taxane Addition To Doxorubicin, Cyclophosphamide Supported In HER2-Negative Early Breast Cancer

A combined analysis of three phase III trials shows the inferiority of doxorubicin plus cyclophosphamide relative to an anthracycline-based regimen incorporating a taxane in patients with early breast cancer

medwireNews: Adding a taxane to the combination of an anthracycline and cyclophosphamide (TaxAC) is associated with improved invasive disease-free survival (IDFS) compared with docetaxel plus cyclophosphamide (TC) in patients with high-risk HER2-negative early breast cancer, show the ABC trials.

Lead author Joanne Blum, from the Baylor University Medical Center, in Dallas, Texas, USA, and co-investigators explain that a previous trial demonstrated the superiority of TC over AC in early breast cancer, but the efficacy of TC relative to anthracycline-based regimens incorporating a taxane is not known.

To determine the noninferiority of TC versus TaxAC in women with high-risk HER2-negative disease, data from three sequential open-label phase III trials – termed the ABC (anthracyclines in early breast cancer) trials – were pooled for a joint efficacy analysis.

In the first trial – US Oncology Research (USOR) 06-090 – participants were randomly assigned to receive docetaxel plus cyclophosphamide without or with doxorubicin for six 21-day cycles (TC6 and TAC6, respectively). The second trial – National Surgical Adjuvant Breast and Bowel Project (NSABP) B-46-I/USOR 07132 – compared three chemotherapy regimens, TC6, TAC6 or TC6 plus bevacizumab , with just the first two groups included in the joint analysis. And the third trial, NSABP B-49, evaluated TC6 relative to several standard TaxAC regimens, chosen by the investigator and patient.

In all, 2125 women were randomly assigned to the TC6 group and 2117 to the TaxAC group, forming the intention-to-treat cohort, with a respective 2094 and 2062  receiving the assigned treatment, the rest being lost to follow-up.

A preplanned interim analysis of the as-treated cohort showed that patients who received TC were more likely to experience invasive disease than their counterparts given TaxAC, at a hazard ratio (HR) of 1.202, which exceeded the predefined inferiority margin of 1.180.

The findings were similar in the intention-to-treat analysis, with an HR of 1.23 for TC6 versus TaxAC.

According to the article published in the Journal of Clinical Oncology, the recurrence-free interval was significantly shorter for TC6-treated women than those given TaxAC (HR=1.51), but at the time of reporting, with a median follow-up of 3.3 years, there was no significant difference between groups in terms of overall survival.

“Survival data are still immature, and longer follow-up times will be necessary to determine the impact on survival”, the researchers write.

And they acknowledge that “[a]lthough results of the ABC trials demonstrated a statistically significant improvement in IDFS with the administration of anthracyclines in patients with HER2-negative disease, the absolute benefits were small, and the majority of patients who received TC6 have done well without an anthracycline.”

Unplanned subgroup analysis of the ABC trials indicated a significant interaction between hormone receptor-positivity and nodal status, such that patients with no positive nodes derived an IDFS benefit from TC6 relative to the TaxAC regimen, whereas the TaxAC combination was favoured in those with one or more nodes.

The investigators note that such an interaction was not evident among those with hormone receptor-negative breast cancer.

And the team comments: “Additional events also will be essential for critical correlative studies of predictive biomarkers or expression profiles, which may identify subsets of patients who derive substantial benefit from inclusion of the anthracyclines and thus help identify a larger subset who could be spared the risk of serious cardiac and long-term hematologic toxicities.”

Reference

Blum JL, Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: the ABC trials—USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol; Advance online publication 11 April 2017. doi: 10.1200/JCO.2016.71.4147

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