medwireNews: Adjuvant treatment with the COX-2 inhibitor celecoxib does not improve the disease outcomes of women with HER2-negative, early breast cancer, shows a phase 3 trial.
“Despite much preclinical evidence suggesting that COX-2 inhibitors would improve the outlook of patients with early breast cancer, this randomized clinical trial found no evidence of benefit when given at a dose of 400 mg per day for 2 years to patients with [HER2]-negative breast cancer,” write the researchers in JAMA Oncology.
They continue: “Longer-term treatment or use of a higher dose of celecoxib may lead to a DFS [disease-free survival] benefit, but further studies would be required to test this possibility.”
R Charles Coombes (Imperial College London, UK) and fellow investigators recruited 2639 women (median age 55.2 years) to the double-blind REACT trial, and randomly assigned them to receive up to 2 years of adjuvant celecoxib or placebo. Participants were required to have undergone a complete resection with no evidence of metastases, and those with hormone receptor-negative disease (27%) were required to have received prior chemotherapy.
At a median follow-up of 74.3 months, there was no significant difference in DFS between the celecoxib and placebo groups, with respective 5-year rates of 84% and 83%, and an unadjusted hazard ratio (HR) of 0.97.
Overall survival was also comparable between the treatment arms, with 5-year rates of 90% and 91% among celecoxib and placebo-treated patients, respectively, and a nonsignificant unadjusted HR of 0.97.
In addition, there was “[n]o evidence of a differential effect” by estrogen receptor status for either survival endpoint, and there was also no significant difference in outcomes by treatment in patients with low or high COX-2 expression, add Coombes and co-researchers.
With regard to safety, they note that “[c]ontrary to expectations, no significant increase in adverse effects was observed; in particular, there was no evidence of an increase in gastrointestinal or cardiac adverse effects with celecoxib.”
The rate of discontinuation due to toxicity was also comparable between the celecoxib and placebo groups, at 13% and 11%, respectively.
Writing in an accompanying editorial, Wendy Chen and Jennifer Ligibel, both from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, note that these findings are “largely consistent” with those of the Canadian Cancer Trials Group MA.27 study of adjuvant celecoxib in patients with hormone receptor-positive disease.
“However, despite the lack of evidence from these 2 large, randomized clinical trials […], the unanswered question regarding aspirin and breast cancer recurrence remains highly relevant,” they comment.
“The ongoing Add-Aspirin and ABC studies will provide important information regarding the effect of aspirin on breast cancer recurrence and all-cause mortality for patients with breast cancer and will shed light on the potential role that inflammation plays in the progression of breast cancer,” conclude the editorialists.
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JAMA Oncol 2021; doi:10.1001/jamaoncol.2021.2193
JAMA Oncol 2021; doi:10.1001/jamaoncol.2021.2056