In the phase III REACT trial reported in JAMA Oncology, R. Charles Coombes, MD, PhD, and colleagues found no disease-free survival benefit with the addition of 2 years of adjuvant celecoxib vs placebo to conventional adjuvant treatment in patients with HER2-negative breast cancer.
R. Charles Coombes, MD, PhD
Study Details
The double-blind trial included 2,639 patients with completely resected breast cancer receiving local and systemic therapy according to local practice. They were randomly assigned 2:1 between January 2007 and November 2012 to receive celecoxib at 400 mg (n = 1,763) or placebo (n = 876) once daily for 2 years.
Patients with node-negative disease and T1 and grade 1 tumors were excluded from the trial. The primary endpoint was disease-free survival.
Key Findings
Cytotoxic chemotherapy was received by 65% of 1,270 patients in the celecoxib group and 68% of 646 in the placebo group with estrogen receptor (ER)-positive disease, and by 99% of 493 patients and 99% of 230 patients, respectively, with ER-negative disease. Patients with hormone receptor–positive disease received endocrine therapy according to local practice.
At a median follow-up of 74.3 months (interquartile range = 61.4–93.6 months), disease-free survival events had occurred in 18% of the celecoxib group vs 19% of the placebo group; estimated 5-year disease-free survival was 84% vs 83% (unadjusted hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.80–1.17, P = .75). Hazard ratios were 0.87 (95% CI = 0.69–1.10) among patients with ER-positive disease and 1.17 (95% CI = 0.85–1.60) among those with ER-negative disease (P = .12 for interaction).
Death occurred in 12% of patients in the celecoxib group vs 12% of the placebo group, with estimated 5-year overall survival rates of 90% vs 91% (HR = 0.97, 95% CI = 0.76–1.22, P = .78). Hazard ratios were 0.85 (95% CI = 0.62–1.15) among ER-positive patients and 1.16 (95% CI = 0.80–1.69) among ER-negative patients (P = .17 for interaction).
Prespecified cardiovascular events occurred in 15% vs 13% of patients. No evidence of excess gastrointestinal toxicity was observed in the celecoxib group. Rates of other toxicities were low in both groups, with no statistical evidence of differences in incidence for any toxic effect.
The investigators concluded, “In this randomized clinical trial, patients showed no evidence of a disease-free survival benefit for 2 years’ treatment with celecoxib compared with placebo as adjuvant treatment of [HER2]-negative breast cancer. Longer-term treatment or use of a higher dose of celecoxib may lead to a disease-free survival benefit, but further studies would be required to test this possibility.”
Dr. Coombes, of the Department of Surgery and Cancer, Imperial College London, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Cancer Research UK, Pfizer, and others. For full disclosures of the study authors, visit jamanetwork.com.
