Anthracyclines in early breast Cancer: The ABC Trials—USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology)

Joanne L. Blum, Patrick J. Flynn, Greg Yothers, Lina Asmar, Charles E. Geyer, Samuel A. Jacobs, Nicholas J. Robert, Judith O. Hopkins, Joyce A. O’Shaughnessy, Chau T. Dang, Henry Leonidas Gómez, Louis Fehrenbacher, Svetislava J. Vukelja, Alan P. Lyss, Devchand Paul, Adam M. Brufsky, Jong Hyeon Jeong, Linda H. Colangelo, Sandra M. Swain, Eleftherios P. MamounasStephen E. Jones, Norman Wolmark

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Purpose Docetaxel and cyclophosphamide (TC) was superior to doxorubicin and cyclophosphamide (AC) in a trial in early breast cancer. However, activity of TC relative to AC regimens with a taxane (TaxAC) is unknown. Methods In a series of three adjuvant trials, women were randomly assigned to TC for six cycles (TC6) or to a standard TaxAC regimen. US Oncology Research (USOR) 06-090 compared TC6 with docetaxel, doxorubicin, and cyclophosphamide (TAC6). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-46-I/USOR 07132 compared TC6, TAC6, or TC6 plus bevacizumab. NSABP B-49 compared TC6 with several standard AC and taxane combination regimens. Before any analysis of individual trials, a joint efficacy analysis of TC versus the TaxAC regimens was planned, with invasive disease-free survival (IDFS) as the primary end point. Patients who received TC6 plus bevacizumab on NSABP B-46-I/USOR 07132 were not included. A hazard ratio (HR) from a stratified Cox model that exceeded 1.18 for TC6 versus TaxAC was predefined as inferiority for TC6. The prespecified interim monitoring plan was to report for futility if the HR was . 1.18 when 334 IDFS events were observed (50% of 668 events required for definitive analysis). Results A total of 2,125 patients were randomly assigned to receive TC6 regimens and 2,117 patients were randomly assigned to receive TaxAC regimens. The median follow-up time was 3.3 years. There were 334 IDFS events, and the HR for TC6 versus TaxAC was 1.202 (95% CI, 0.97 to 1.49), which triggered early reporting for futility. The 4-year IDFS was 88.2% for TC6 and was 90.7% for TaxAC (P = .04). Tests for treatment interaction by protocol, hormone receptor status, and nodal status were negative. Conclusion The TaxAC regimens improved IDFS in patients with high-risk human epidermal growth factor receptor 2–negative breast cancer compared with the TC6 regimen.

Original languageEnglish (US)
Pages (from-to)2647-2655
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number23
DOIs
StatePublished - Aug 10 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Blum, J. L., Flynn, P. J., Yothers, G., Asmar, L., Geyer, C. E., Jacobs, S. A., Robert, N. J., Hopkins, J. O., O’Shaughnessy, J. A., Dang, C. T., Gómez, H. L., Fehrenbacher, L., Vukelja, S. J., Lyss, A. P., Paul, D., Brufsky, A. M., Jeong, J. H., Colangelo, L. H., Swain, S. M., ... Wolmark, N. (2017). Anthracyclines in early breast Cancer: The ABC Trials—USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). Journal of Clinical Oncology, 35(23), 2647-2655. https://doi.org/10.1200/JCO.2016.71.4147