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Original Investigation
July 15, 2021

Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer: The REACT Randomized Clinical Trial

Author Affiliations
  • 1Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
  • 2Department of Digestion, Metabolism and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
  • 3Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, United Kingdom
  • 4Guy’s and St Thomas’ National Health Service Foundation Trust and Biomedical Research Centre, King’s College, London, United Kingdom
  • 5University of Liverpool and Clatterbridge Cancer Centre, Liverpool, United Kingdom
  • 6Ontario Institute for Cancer Research, Toronto, Ontario, Canada
  • 7Edinburgh Cancer Research Centre, Edinburgh, United Kingdom
  • 8National Health Service Lanarkshire, Lanarkshire, United Kingdom
  • 9Mount Vernon Cancer Centre, Northwood, United Kingdom
  • 10Breast Unit, Poole Hospital National Health Service Foundation Trust, Poole, United Kingdom
  • 11German Breast Group, Neu-Isenburg, Germany
  • 12Charité University Hospital and German Cancer Consortium, Berlin, Germany
  • 13United Lincolnshire Hospitals National Health Service Trust, Lincolnshire, United Kingdom
  • 14University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry, United Kingdom
  • 15University of Sheffield, Sheffield, United Kingdom
  • 16Velindre Cancer Centre, Cardiff, United Kingdom
  • 17Universitatsmedizin Mainz, Mainz, Germany
  • 18Universitatsklinikum Freiburg, Freiburg, Germany
  • 19Stiftung Rehabilitation Heidelberg, Zentralkilikum Suhl GmbH, Suhl, Germany
JAMA Oncol. 2021;7(9):1291-1301. doi:10.1001/jamaoncol.2021.2193
Visual Abstract. Effect of celecoxib vs placebo as adjuvant therapy on disease-free survival among patients with breast cancer
Effect of celecoxib vs placebo as adjuvant therapy on disease-free survival among patients with breast cancer
Key Points

Question  Is there a benefit for patients who receive celecoxib as an addition to conventional therapy for women with ERBB2 (formerly HER2)–negative primary breast cancer?

Findings  In this randomized clinical trial, 2639 patients were randomized 2:1 to receive treatment with celecoxib or placebo for 2 years. Disease-free survival events were reported for 487 patients (19%): 18% for those receiving celecoxib vs 19% for those receiving placebo, a nonsignificant difference.

Meaning  Overall, no benefit was observed for patients who received celecoxib compared with placebo as adjuvant therapy for unselected ERBB2-negative primary breast cancer.


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

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