As reported by Joanne L. Blum, MD, PhD, of Baylor University Medical Center, Texas Oncology, and colleagues in the Journal of Clinical Oncology, the efficacy analysis of the combined adjuvant Anthracyclines in Early Breast Cancer (ABC) Trials showed better invasive disease-free survival with taxane plus doxorubicin/cyclophosphamide (TaxAC) regimens vs six cycles of docetaxel/cyclophosphamide (TC6) in high-risk HER2-negative breast cancer. The analysis was conducted after the prespecified futility boundary for demonstrating noninferiority of TC6 was crossed at interim analysis.
The three phase III ABC studies consist of U.S. Oncology Research (USOR) 06-090, National Surgical Adjuvant Breast and Bowel Project (NSABP) B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). USOR 06-090 compared TC6 with docetaxel, doxorubicin, and cyclophosphamide (TAC6). NSABP B-46-I/USOR 07132 compared TC6, TAC6, or TC6 plus bevacizumab (Avastin). NSABP B-49 compared TC6 with several standard AC-plus-taxane regimens. The primary aim of the trials was to determine whether TC6 was noninferior to TaxAC regimens.
Prior to analysis of individual trials, a joint efficacy analysis of TC6 vs TaxAC regimens was planned using invasive disease–free survival as the primary endpoint and excluding patients who received bevacizumab. The predefined inferiority threshold for TC6 was a hazard ratio > 1.18; a prespecified interim analysis stipulated futility if the hazard ratio was > 1.18 when 50% of events (334 events) for full analysis had occurred.
Invasive Disease–Free Survival
In the 3 trials, 2,125 patients were randomized to TC6 and 2,117 were randomized to TaxAC regimens. Median follow-up was 3.3 years. At interim analysis at 334 invasive disease–free survival events, the hazard ratio for invasive disease–free survival for TC6 vs TaxAC was 1.202 (95% confidence interval [CI] = 0.97–1.49), resulting in early reporting of futility. The hazard ratio on the basis of intent-to-treat analysis for all data available at the time of efficacy analysis (through October 2015) was 1.23. Overall, 4-year invasive disease–free survival was 88.2% among patients receiving TC6 and 90.7% among those receiving TaxAC regimens (P = .04).
The investigators concluded: “The TaxAC regimens improved [invasive disease–free survival] in patients with high-risk human epidermal growth factor receptor 2–negative breast cancer compared with the TC6 regimen.”
They further stated: “Although results of the ABC trials demonstrated a statistically significant improvement in [invasive disease–free survival] 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.”
Noting that the median follow-up time for the largest of the studies (NSABP B-49) is only 2.2 years and that the trial has contributed only 25% of the total observed events, the investigators emphasized that additional follow-up is needed for a fuller understanding of the findings.
Blum JL, et al: J Clin Oncol. April 11, 2017 (early release online). ■