Docetaxel plus cyclophosphamide fails to meet non-inferiority vs. anthracycline/taxane chemotherapy

At the 2016 ASCO Annual Meeting, Adam M. Brufsky, MD, PhD, professor of medicine, associate chief of hematology/oncology and co-director of the comprehensive breast cancer center at the University of Pittsburgh, spoke with HemOnc Today about the data from adjuvant trials presented during the Breast Cancer — Triple-Negative/Cytotoxics/Local Therapy oral abstract session. In this article – the first in a 3-part series – Brufsky discusses the presentation on the interim joint analysis of the anthracyclines in early breast cancer (ABC) phase III trials.

Non-anthracycline regimen fails to demonstrate non-inferiority in 3-year analysis

Adam M. Brufsky

The ABC adjuvant trials examined whether a regimen of docetaxel plus cyclophosphamide for 6 cycles was non-inferior to the combination regimens of doxorubicin and cyclophosphamide with docetaxel or paclitaxel among women with resected, high-risk, HER-2–negative breast cancer. Participants were pooled from 3 trials: USOR 06-090 (n = 1,295), NSABP B-46I/USOR 07132 (n = 1,077) and NSABP B-49 (1,870).

The primary endpoint was invasive DFS, which was defined by the researchers as time to local, regional or distant recurrence, invasive contralateral breast cancer, second primary cancer or death. Patients were stratified according to the original trial they were included in; node positivity (0, 1-3, 4-9 or 10+); and hormonal status (positive or negative). The researchers pre-specified an HR from a stratified Cox model of 1.18 or more as inferior; HRs greater than 1 were determined to be in favor of anthracycline/taxane-based chemotherapy regimens. The interim monitoring plan set by the researchers involved reporting early for futility if the HR was > 1.18 when 50% (n = 334) of the planned invasive DFS events (n = 668) had occurred.

The presentation by Joanne L. Blum, MD, PhD, FACP, included results from a total of 4,130 patients; 2,078 patients were randomized to receive docetaxel plus cyclophosphamide and 2,052 were randomized to receive anthracycline/taxane-based chemotherapy. Patient and tumor characteristics were “balanced by treatment,” according to the study results: 69% of patients had hormone-positive disease, 41% had node-negative disease and 51% had high-grade tumors. Median follow-up was 3.2 years.

Early futility was reported after 334 invasive DFS events occurred (observed HR for docetaxel plus cyclophosphamide vs. anthracycline/taxane-based chemotherapy = 1.202; 95% CI, 0.97-1.49). Three-year invasive DFS was 91.7% for docetaxel plus cyclophosphamide vs. 92.4% for anthracycline/taxane-based chemotherapy.

Questions remain regarding use of anthracyclines in adjuvant therapy

The results of this analysis were “very eagerly” anticipated, according to Brufsky, a HemOnc Today editorial board member who also served as a study investigator.

“The take-home message is that docetaxel plus cyclophosphamide did not meet the boundary for non-inferiority, meaning that it still is not considered to be equivalent to anthracycline/taxane-based chemotherapy,” Brufsky said. “What was also interesting is that most of the non-meeting of the criteria came from the ER-negative subset of patients. In the ER-positive subset of patients, they both did very well and there really was not much of a difference between both arms.”

However, the full impact of these findings has yet to be elucidated because of the relatively short follow-up period.

“We really need to wait a little bit longer before we say that anthracyclines should either continue to be part of – or not be part of – adjuvant therapy, at least in anthracycline/taxane-based chemotherapy,” Brufsky said. – by Julia Ernst, MS

Reference:

Blum JL, et al. Abstract 1000. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclosure: Blum and Brufsky report no relevant financial disclosure. Please see the full study for a list of all other authors’ relevant financial disclosures.