Joanne L. Blum, MD, PhD
Phase III findings show that, in patients with high-risk, HER2-negative breast cancer, treatment with a taxane combined with anthracycline (TaxAC) was found to show a higher disease-free survival (DFS) benefit versus docetaxel plus cyclophosphamide (TC).
The phase III ABC trials, which were presented during the 2016 ASCO Annual Meeting, included USOR 06-090, NSABP B-46I/USOR 07132, and NSABP B-49. The studies randomized patients to a TaxAC regimen of doxorubicin or cyclophosphamide plus docetaxel or paclitaxel (n = 2052) or TC (n = 2078). The primary endpoint was invasive DFS. Patient and tumor characteristics were balanced by treatment, as 69% were hormone receptor (HR)-positive, 41% were node-negative, and 51% were of high-grade disease.
At a median follow-up of 3.2 years and 334 invasive DFS events, the hazard ratio for TC versus TaxAC was 1.202 (95% CI, .97-1.49). The 3-year invasive DFS rate was 91.7% and 92.4% for TC and TaxAC, respectively.
Additionally, the benefit observed with TaxAC over TC was more pronounced in patients with HR-positive tumors with more than 4 positive nodes, according to lead investigator Joanne L. Blum, MD, PhD.
In an interview with OncLive
, Blum, an oncologist and hematologist at Texas Oncology, discusses the design and phase III results from the ABC trials, and what impact the encouraging findings could have in patients with HER2-negative breast cancer.
OncLive: What were the main findings of the ABC trials?
: The ABC trials were three trials that were done in sequence. These three trials examined TaxAC regimens versus TC times 6. The initial 06-090 trial, which has the longest median follow-up of all the trials of about 6.3 years, was then followed by B-46-I 07132. I should preface that by saying that this was a collaboration with US Oncology Research, as well as the NSABP (National Surgical Adjuvant Breast and Bowel Project). This second trial has a median follow-up of 4.8 years.
The B-46-I trial also had a third arm, which was TC bevacizumab (Avastin), and those data are not analyzed in the ABC trial's presentation. The third trial was B-49. This trial rapidly completed accrual in 2013 and has the shortest median follow-up of all of the trials at about 2.2 years.
In aggregate, we had over 4200 patients enrolled in the trial. We have over 4100 analyzed currently. The trial schema included both high-risk node-negative patients, as well as node-positive patients. The trial prespecified stratification variables included the number of positive nodes, 0, 1 to 3, 4 to 9, or 10 more, ER- or PR-positive, or ER/PR-negative. Also, another stratification variable was the trial from which the patients were derived.
The original 2 trials, 06-090 and B-46-I 07132, allowed only for the TaxAC arm every 3 weeks times 6 versus TC. Arm one was tax. In B-49, 4 regimens were allowed. These included the TaxAC regimen every 3 weeks times 6, or AC every 2 weeks followed by weekly paclitaxel times 12, or AC every 3 weeks followed by paclitaxel times 12, or AC dose dense followed by paclitaxel dose dense. The 06-090 and B-46-I 07132 trials just had the TaxAC arm and B-49 allowed all 4 arms.
Median follow-up was 6.3 years for 06-090, 4.8 for B-46-I, and 2.2 years for the B-49 trial. The overall median follow-up is 3.2 years. The number of patients that were node negative was 41%, 44% had 1-3 positive nodes, 11% had 4 to 9 positive nodes, and 4% had 10 or more positive nodes. The data was as of October 31, 2015, and at that time we had 399 events, which exceeded the prespecified 334 events. The initial analysis was done for the primary endpoint, which was invasive disease-free survival. At that time, the hazard ratio was 1.202, which exceeded the pre-specified hazard ratio of 1.18 for futility of TC versus TaxAC. Therefore, the trial was deemed ready for the initial presentation.
The results from the trial, that the overall hazard ratio for the 334 patients was over 1.2, were presented. The data we presented was from all 399 patients, and what we saw was that there were more events in the TC arm relative to the TaxAC arm. The overall hazard ratio was 1.23. The curves begin to diverge at 2 to 3 years, the hazard ratio for the primary endpoint was statistically significant with a P value of .04 favoring TC.
The other thing we analyzed was the forest plot for the prespecified stratification variables. What we saw was that the hazard ratios favored TaxAC for both 06-090 and B-46-I with hazard ratios of 1.31 and 1.34 respectively. However, for B-49, which has the shortest follow-up with 2.2 years, the hazard ratio is 1.
For ER/PR-negative patients, the hazard ratio was strongly supportive of TaxAC. It was also positive for the hormone receptor-positive group, but less so. Node-negative patients had a hazard ratio of 1, but for 1 to 3 positive nodes, 4 to 9, and 10, the hazard ratio is progressively moved further to the right.