Celecoxib Shows No Evidence for DFS Benefit Over 10 Years in ERBB2-Negative Breast Cancer

Looking at 2 years' worth of data for patients with ERBB2-negative breast cancer, a study showed that the anti-inflammatory agent celecoxib had no disease free survival benefit.

In a trial comparing 2 years of treatment on celecoxib (Celebrex), an anti-inflammatory agent, to placebo as adjuvant therapy for patients with ERBB2-negative breast cancer no evidence of a disease-free survival (DFS) benefit was seen, according to research in JAMA Oncology.1

The REACT trial (NCT02429427) was a phase 3 2:1 randomized, double-blinded study that was conducted across 160 centers in the United Kingdom and Germany looking at the efficacy of adjuvant celecoxib vs placebo among a total of 2,639 patients. These patients had completely resected breast cancer with prior local and systemic therapy with a median age of 55 years old.

Most patients' tumors (73%) had estrogen receptor positive disease or progesterone receptor positive and ERBB2 negative disease and 1,265 patients had node positive disease, while 1,111 patients had grade 3 tumors. When splitting up the total patient population 1,763 patients received celecoxib compared to 876 on placebo.

“Patients with breast cancer remain at risk of relapse after adjuvant therapy,” the researchers noted. Celecoxib has been believed to impact certain pathways, such as cyclooxygenase-2, as an anti-inflammatory agent since inflammatory cells are found in the microenvironment of the tumor.2 “Celecoxib has shown antitumor effects in preclinical models of human breast cancer, but clinical evidence is lacking,” the researchers wrote. This phase 3 trial would see if the addition of the anti-inflammatory agent to standard of care therapy would impact the patient’s DFS.

The primary end point of this study was DFS and at a median follow up of 74.3 months, DFS events had been reported in just 487 patients, or 19% of the intention-to-treat population. In the treatment arm 18% (n = 323) had a DFS event with a DFS rate of 84% among those that responded, whereas in the placebo arm 19% (164) of patients had a DFS event with a 83% DFS rate in this group (HR 0.97: 95% CI, 0.80-1.17, P = .75).

“Results of abundant clinical studies, although unconvincing, suggest that celecoxib administration is related not only to diminished incidence of cancer but also to the better prognosis in cancer patients,” previous research had cited.3 “In view of the potential variations in response to celecoxib in cancer patients, it seems critical to ascertain target populations for its use.”

For the researchers in the REACT trial, this was not enough support to show a DFS benefit in the 2 year period that patients were observed. According to the researchers, it may still be possible for longer term treatments with celecoxib to yield DFS benefit, but there would need to be further, and potentially wider, studies to test the possibility of this drug in the adjuvant setting.


1. Coombes RC, Tovey H, Kilburn L, et al. Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer: The REACT Randomized Clinical Trial. JAMA Oncol. 2021 Sep 1;7(9):1291-1301. doi: 10.1001/jamaoncol.2021.2193

2. Tołoczko-Iwaniuk N, Dziemiańczyk-Pakieła D, Nowaszewska BK, Celińska-Janowicz K, Miltyk W. Celecoxib in Cancer Therapy and Prevention - Review. Curr Drug Targets. 2019;20(3):302-315. doi: 10.2174/1389450119666180803121737

3. Li J, Hao Q, Cao W, Vadgama JV, Wu Y. Celecoxib in breast cancer prevention and therapy. Cancer Manag Res. 2018 Oct 26;10:4653-4667. doi: 10.2147/CMAR.S178567