TWO YEARS of treatment with celecoxib had no observed effect on 5-year outcomes of patients with early breast cancer in the large REACT trial presented at the 2017 San Antonio Breast Cancer Symposium.¹

“There was no overall benefit observed in disease-free survival or overall survival for celecoxib vs placebo,” said lead author R. Charles Coombes, MD, PhD, Professor of Medical Oncology at Imperial College London. “We were gratified by the low risk of breast cancer recurrence in the overall population,” he noted.

“There was no overall benefit in disease-free survival or overall survival for celecoxib vs placebo.”

— R. Charles Coombes, MD, PhD

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“Celecoxib was not associated with significant toxicity, except for a slight nonsignificant increase in dyspnea,” Dr. Coombes added. “A benefit of celecoxib was the relief of arthralgia, which is common in women treated with aromatase inhibitors.”

Inflammation has long been associated with progression of breast cancer. Randomized studies have suggested that aspirin may slow disease progression, and preclinical studies suggest that COX2 inhibition may attenuate the breast cancer process. The large REACT trial was mounted to evaluate the effect of COX2 inhibition vs placebo in reducing the risk of breast cancer recurrence.

Study Details

THE STUDY enrolled patients with primary breast cancer, excluding those with HER2-positive disease or stage I, node-negative, grade 1 tumors. All patients had complete surgical resection and were treated according to local practice prior to study entry. Prior chemotherapy and concurrent radiotherapy were each permitted, and patients with hormone receptor–positive tumors received endocrine therapy.

Patients were randomized 2:1 to receive celecoxib at 400 mg once a day or placebo for 2 years. Baseline characteristics of the two groups were similar, Dr. Coombes said. Median age was 55 years; 50% of patients had tumors greater than 2 cm; 42% had grade 3 tumors; and 48% had node-positive disease. About three-quarters were estrogen receptor–positive, and 75% received some form of chemotherapy.

Between January 2007 and November 2012, 2,639 patients were randomized at 181 centers across the United Kingdom and Germany; 1,763 received celecoxib and 876, placebo. With a median follow-up of 5 years, 452 disease-related events had occurred, and 80% of patients completed their assigned treatment.

No significant differences were observed between the two groups for 5-year disease-free survival rate in the intent-to-treat population: 83% for celecoxib vs 83% for placebo. The 5-year disease-free survival rate in patients with estrogen receptor–positive disease was 88% vs 86% for celecoxib and placebo, respectively. Within the estrogen receptor–negative cohort, the 5-year disease-free survival rate was 72% vs 75%, respectively.

Overall survival at 5 years was not statistically different between groups: 90% and 91% for celecoxib and placebo, respectively.

Safety Profile

AMONG NONRELAPSED patients, there were 36 (2%) deaths in the celecoxib group and 18 (2%) in the placebo group. None of the deaths were due to gastrointestinal causes. Two patients in each group died of cardiac causes.

Celecoxib was not associated with significant toxicity compared with placebo in these patients with early breast cancer. A total of 304 serious adverse events were reported in 265 patients: 186 (10.6%) of 1,763 celecoxib-treated patients and 79 (9%) of 876 placebo patients. Serious adverse events related to cardiac function were reported in 12 celecoxib patients and 7 placebo patients; serious adverse events related to gastrointestinal problems were reported in 9 and 2 patients, respectively.

No toxicities were statistically significantly different between groups. Although nonsignificant, it appeared that more dyspnea was seen in the celecoxib-treated group, and more arthralgia was observed in controls. ■

DISCLOSURE: Dr. Coombes reported no conflicts of interest.

REFERENCE

1. Coombes RC, Tovey H, Kilburn L, et al: 2017 San Antonio Breast Cancer Symposium. Abstract GS3-03. Presented December 7, 2017.