Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer

Abstract

for the Randomized European Celecoxib Trial (REACT) Trial Management Group and Investigators 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 PARTICIPANTSThe 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 MEASURESThe 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 RELEVANCEIn 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.

The Prostaglandin E2 Pathway and Breast Cancer Stem Cells: Evidence of Increased Signaling and Potential Targeting

“…There have been several clinical trials using the COX-2 inhibitor celecoxib completed in the treatment of breast cancer ( 95 , 96 ). One study showed promising results with decreased metastasis, angiogenesis, and inflammation when given perioperatively ( 96 ).…”

“…In a phase II trial, pre-treatment and post-treatment breast biopsies revealed that celecoxib induces transcription of genes associated with anti-tumour and decreased cell proliferation ( 97 ). However, in another study patients treated long-term with celecoxib had no significant difference in disease-free survival compared to placebo group ( 95 ). Hence, further studies are needed to clarify the potential clinical impact of targeting this pathway.…”

“…There have been several clinical trials using the COX-2 inhibitor celecoxib completed in the treatment of breast cancer (95,96).…”

Association of Preoperative Serum Levels of CEA and CA15-3 with Molecular Subtypes of Breast Cancer

“…In China, rates of breast cancer incidence and mortality have been accelerating over years and which were projected to increase modestly in the future [ 2 ]. Although there is a surge in the incidence of breast cancer, however, timely detection and the use of effective systemic adjuvant therapy while following prognostic factors have improved breast cancer prognosis [ 3 , 4 ]. Cancer antigen 15-3 (CA15-3) in addition to carcinoembryonic antigen (CEA) along with cancer antigen 125 (CA125) are extensively used in the clinical practice of breast cancer as serum tumor markers.…”

Can Acute Postoperative Pain Management After Tumour Resection Surgery Modulate Risk of Later Recurrence or Metastasis?

“…The authors concluded that longer-term treatment or use of a higher dose of celecoxib may lead to a disease-free benefit. Further high-powered clinical trials would be required to further investigate this ( 125 ).…”