Celecoxib may be contraindicated for some breast cancer patients
medwireNews: Use of the cyclooxygenase 2 (COX-2) inhibitor celecoxib during neoadjuvant taxane-based chemotherapy is associated with adverse survival outcomes in certain subgroups of patients with breast cancer, shows a post-hoc analysis of the REMAGUS02 trial.
As described in the Journal of Clinical Oncology, the analysis was restricted to trial participants who had HER2-negative disease and available data on the pretreatment expression levels of the prostaglandin-endoperoxide synthase 2 gene (PTGS2; another name for the COX2 gene). This gave a study cohort of 156 patients, all of whom received neoadjuvant chemotherapy with epirubicin plus cyclophosphamide followed by docetaxel, but only half received celecoxib alongside the taxane as per the random assignment.
Over a median follow-up of 94.5 months, event-free survival (EFS) was significantly worse for patients who did versus did not receive celecoxib, at a hazard ratio (HR) of 1.70, but this association was significantly modified by PTGS2 expression.
Specifically, among participants with low levels of PTGS2 expression, the addition of celecoxib to chemotherapy was associated with significantly shorter EFS, with an HR of 3.01, but this was not the case for those with high PTGS2 expression levels.
And even in the PTGS2-low group, there was a difference by oestrogen receptor (ER) status, such that EFS was significantly worse with celecoxib use among patients who had ER-negative disease (HR=13.45), but not for those with ER-positive breast cancer.
The results were similar for overall survival, say Fabien Reyal, from Institut Curie in Paris, France, and fellow investigators, who believe that the study findings “raise concerns about the safety of COX-2 inhibitors during chemotherapy in patients with breast cancer.”
Of note, the clinical observations were confirmed in the laboratory, such that when celecoxib was used alongside docetaxel in breast cancer cell lines that had low PTGS2 expression, cellular viability was better than when just docetaxel was used. No such effect of celecoxib on cellular viability in the presence of docetaxel was observed in PTGS2-high cell lines, report the investigators.
They therefore write: “In the absence of other evidence, we recommend avoidance of celecoxib use and preference for alternative drugs in patients with ER-negative, HER2-negative breast tumors who are receiving docetaxel-containing [neoadjuvant chemotherapy], unless the expected benefit greatly outweighs the potential risks.”
Reyal et al stress, however, that the study results are “hypothesis-generating”, and additional research is needed, including “post hoc reanalysis of randomized trials that evaluated COX-2 inhibitors in addition to chemotherapy after stratification by COX-2 expression.”
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