No Survival Benefit with Celecoxib versus Placebo for ERBB2-negative Primary Breast Cancer

According to the REACT randomized clinical trial findings, celecoxib as adjuvant therapy for unselected ERBB2-negative primary breast cancer showed no disease-free survival (DFS) benefit over placebo (JAMA Oncol. 2021 Jul 15:e212193.).

“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,” explained R. Charles Coombes, MD, PhD, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, United Kingdom, and colleagues. 

REACT was a phase 3, randomized, double-blind study conducted in 160 centers across the UK and Germany. Between January 2007 and November 2012, 2639 patients with completely resected breast cancer with local and systemic therapy were recruited with a follow-up of 10 years after treatment completion. Patients with ERBB2-positive or node-negative and T1, grade 1 tumors were not eligible. 

Patients were randomized 2:1 to receive either celecoxib (400mg) or placebo once daily for two years; the statistical analysis was performed from May 2019 to March 2020. 

DFS analyzed in the intention-to-treat population using Cox proportional hazards regression, and log-rank analysis was the primary end point.

1763 of the 2639 patients recruited received celecoxib, while  876 received placebo. Most patient tumors were estrogen or progesterone receptor-positive and ERBB2-negative. Furthermore, 1265 patients (48%) had node-positive disease, and 1111 (42%) had grade 3 tumors.

At the median follow-up of 74.3 months, 487 patients (19%) reportend DFS events: 18% in the celecoxib arm (n= 323; 5-year DFS rate = 84%) and 19% in the placebo arm (n = 164; 5-year DFS rate = 83%; hazard ratio [HR] 0.97 [(95% CI, 0.80-1.17; log-rank P = .75]).

The rates of toxic effects were low in both groups.

“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,” concluded Dr Coombes et al.
—Alexandra Graziano