As reported in JAMA by Wendy Y. Chen, MD, MPH, and colleagues, interim analysis of the phase III Alliance A011502 trial has shown no invasive disease–free survival benefit with adjuvant aspirin vs placebo in patients with high-risk nonmetastatic breast cancer. The trial was suspended early due to futility.
As stated by the investigators, “Observational studies of survivors of breast cancer and prospective trials of aspirin for cardiovascular disease suggest improved breast cancer survival among aspirin users, but prospective studies of aspirin to prevent breast cancer recurrence are lacking.”
Wendy Y. Chen, MD, MPH
Study Details
In the double-blind trial, 3,020 patients from sites in the United States and Canada were randomly assigned between January 2017 and December 2020 to receive 300 mg of aspirin (n = 1,510) or placebo once daily (n = 1,510) for 5 years. Patients must have completed all local therapy and chemotherapy; continuation of endocrine therapy was permitted. The primary outcome measure was invasive disease–free survival.
Key Findings
The data and safety monitoring committee recommended suspending the study at first interim analysis, when the hazard ratio for invasive disease–free survival was found to cross the prespecified futility boundary. At a median follow-up of 33.8 months (range = 0.1–72.6 months), invasive disease–free survival events had occurred in 141 patients in the aspirin group vs 112 in the placebo group (hazard ratio [HR] = 1.27, 95% confidence interval [CI] = 0.99–1.63, P = .06).
For the aspirin group vs the placebo group, invasive disease–free survival events consisted of death in 12 vs 4 patients; invasive disease progression in 104 vs 89, including local recurrence only in 27 vs 22 and distant disease in 77 vs 67; and a new primary event in 25 vs 19, including contralateral breast cancer in 2 vs 7. None of the differences was statistically significant.
No difference in overall survival was observed. Death occurred in 63 patients in the aspirin group vs 52 in the placebo group (HR = 1.19, 95% CI = 0.82–1.72, P = .36). A total of 81 deaths were due to breast cancer, including 46 in the aspirin group and 35 in the placebo group.
Grade ≥ 3 adverse events occurred in 9.3% of patients in the aspirin group vs 10.2% of the placebo group; the most common side effect was vascular events in both groups (1.8% vs 1.5%). Dose reductions to 100 mg due to adverse events occurred in 2.3% vs 2.2% of patients, respectively.
The investigators concluded: “Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. Despite its promise and wide availability, aspirin should not be recommended as an adjuvant breast cancer treatment.”
Dr. Chen, of Dana-Farber Cancer Institute, is the corresponding author for the JAMA article.
Disclosure: The study was supported by the Department of Defense Breast Cancer Research Program, National Cancer Institute, and Bayer. For full disclosures of the study authors, visit jamanetwork.com.
