Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer: The REACT Randomized Clinical Trial.
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Embargo End Date
ICR Authors
Authors
Coombes, RC
Tovey, H
Kilburn, L
Mansi, J
Palmieri, C
Bartlett, J
Hicks, J
Makris, A
Evans, A
Loibl, S
Denkert, C
Murray, E
Grieve, R
Coleman, R
Borley, A
Schmidt, M
Rautenberg, B
Kunze, CA
Rhein, U
Mehta, K
Mousa, K
Dibble, T
Lu, XL
von Minckwitz, G
Bliss, JM
Randomized European Celecoxib Trial (REACT) Trial Management Group and Investigators,
Tovey, H
Kilburn, L
Mansi, J
Palmieri, C
Bartlett, J
Hicks, J
Makris, A
Evans, A
Loibl, S
Denkert, C
Murray, E
Grieve, R
Coleman, R
Borley, A
Schmidt, M
Rautenberg, B
Kunze, CA
Rhein, U
Mehta, K
Mousa, K
Dibble, T
Lu, XL
von Minckwitz, G
Bliss, JM
Randomized European Celecoxib Trial (REACT) Trial Management Group and Investigators,
Document Type
Journal Article
Date
2021-09-01
Date Accepted
2021-04-26
Abstract
IMPORTANCE: Patients with breast cancer remain at risk of relapse after adjuvant therapy. Celecoxib has shown antitumor effects in preclinical models of human breast cancer, but clinical evidence is lacking. OBJECTIVE: To evaluate the role of celecoxib as an addition to conventional therapy for women with ERBB2 (formerly HER2)-negative primary breast cancer. DESIGN, SETTING, AND PARTICIPANTS: The Randomized European Celecoxib Trial (REACT) was a phase 3, randomized, double-blind study conducted in 160 centers across the UK and Germany testing 2 years of adjuvant celecoxib vs placebo among 2639 patients recruited between January 19, 2007, and November 1, 2012, with follow-up 10 years after treatment completion. Eligible patients had completely resected breast cancer with local and systemic therapy according to local practice. Patients with ERBB2-positive or node-negative and T1, grade 1 tumors were not eligible. Randomization was in a 2:1 ratio between celecoxib or placebo. Statistical analysis was performed from May 5, 2019, to March 5, 2020. INTERVENTIONS: Patients received celecoxib, 400 mg, or placebo once daily for 2 years. MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival (DFS), analyzed in the intention-to-treat population using Cox proportional hazards regression and log-rank analysis. Follow-up is complete. RESULTS: A total of 2639 patients (median age, 55.2 years [range, 26.8-86.0 years]) were recruited; 1763 received celecoxib, and 876 received placebo. Most patients' tumors (1930 [73%]) were estrogen receptor positive or progesterone receptor positive and ERBB2 negative. A total of 1265 patients (48%) had node-positive disease, and 1111 (42%) had grade 3 tumors. At a median follow-up of 74.3 months (interquartile range, 61.4-93.6 years), DFS events had been reported for 487 patients (19%): 18% for those who received celecoxib (n = 323; 5-year DFS rate = 84%) vs 19% for those who received placebo (n = 164; 5-year DFS rate = 83%); the unadjusted hazard ratio was 0.97 (95% CI, 0.80-1.17; log-rank P = .75). Rates of toxic effects were low across both treatment groups, with no evidence of a difference. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, patients showed no evidence of a DFS benefit for 2 years' treatment with celecoxib compared with placebo as adjuvant treatment of ERBB2-negative breast cancer. Longer-term treatment or use of a higher dose of celecoxib may lead to a DFS benefit, but further studies would be required to test this possibility. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02429427 and isrctn.org Identifier: ISRCTN48254013.
Citation
JAMA oncology, 2021, 7 (9), pp. 1291 - 1301
Source Title
Publisher
AMER MEDICAL ASSOC
ISSN
2374-2437
eISSN
2374-2445
Collections
Research Team
Clinical Trials & Statistics Unit