CHICAGO — Interim joint analysis of the ABC Trials — 3 phase 3 trials that compared docetaxel plus cyclophosphamide (TC) to anthracycline/taxane-based chemotherapy regimens (TaxAC) in women with high-risk, HER2-negative breast cancer — showed “invasive disease-free survival was significant for superiority of TaxAC relative to TC,” according to study results presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.1
“Additional follow-up and correlative studies to identify biomarkers of anthracycline benefit will be crucial for fully determining the utility of anthracyclines across this heterogeneous patient population,” said Joanne Lorraine Blum, MD, PhD, US Oncology Research, and Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, Texas.
US Oncology Research and the National Surgical Adjuvant Breast and Bowel Project (NSABP) collaborated with separate sponsors, Sanofi, Genentech, and the National Cancer Institute, on 3 sequential clinical trials that randomly assigned women with high-risk, early stage breast cancer to receive 6 cycles of TC or one of several standard combination regimens of doxorubicin/cyclophosphamide with docetaxel or paclitaxel (TaxAC).
A total of 1870 patients from the NSABP B-49 study were combined with 1077 from the NSABP B-46-I/USOR 07132 studies and 1295 from the US Oncology Research 06-090 study, for a total of 4242 patients. Primary end point was invasive disease-free survival, defined as time to local, regional, or distant recurrence, invasive contralateral breast cancer, second primary cancer, or death.
Patients were stratified for parent trial, positive nodes (0, 1-3, 4-9, 10+), and hormonal status (negative or positive).
The data cut-off for the interim analysis was October 31, 2015. At this time, 399 invasive disease-free survival events of the required 668 events (59.7%) for definitive analysis had been reported, exceeding the prespecified number of 334.
The observed hazard ratio (HR) on these initial 334 events was 1.202, which exceeded the prespecified threshold for futility, defined as >1.18, Dr. Blum said, which “triggered consideration for early reporting.”
A total of 4130 patients began assigned therapy — 2094 randomly assigned to docetaxel plus cyclophosphamide and 2062 to TaxAC — and comprise the analysis set. Patient and tumor characteristics were balanced by treatment; 69% were hormone positive, 41% were node negative, and 51% had high-grade tumors.
The 4-year invasive disease-free survival rate was 88.2% for TC vs 90.7% for TaxAC (HR, 1.23; 95% CI, 1.01-1.50; P = .04). The 4-year overall survival rates were 94.7% for TC and 95.0% for TaxAC (HR, 1.08; 95% CI, 0.82-1.41; P = .60).
Exploratory subgroup analyses suggest that TaxAC regimens provide minimal, if any, benefit in estrogen receptor (ER)-positive/node negative cohorts; a small benefit in ER-positive/1-3 node positive, and ER-negative/node negative cohorts; and a large benefit in ER-positive, 4 or more node positive, and ER-negative/node positive cohorts, she said.
Acute leukemia occurred as the first event in 5 of 2050 patients (0.24%) assigned to TaxAC and in none assigned to TC.
1, Blum JL, Flynn PJ, Yothers G, et al. Interim joint analysis of the ABC (anthracyclines in early breast cancer) phase III trials (USOR 06-090, NSABP B-46I/USOR 07132, NSABP B-49 [NRG Oncology]) comparing docetaxel + cyclophosphamide (TC) v anthracycline/taxane-based chemotherapy regimens (TaxAC) in women with high-risk, HER2-negative breast cancer. Oral presentation at: 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL.