Hamy AS, et al. - The association between prostaglandin-endoperoxide synthase 2 (PTGS2) expression, celecoxib use during neoadjuvant chemotherapy (NAC), and both event-free survival (EFS) and overall survival (OS) were assessed in this cohort analysis. Researchers noted an adverse effect of using celecoxib during chemotherapy on survival in patients with breast cancer; this effect was more pronounced in PTGS2-low and/or estrogen receptor–negative tumors. Patients with breast cancer who are undergoing NAC should ideally not receive cyclooxygenase 2 (COX-2) inhibitors during docetaxel use.

Methods

• From the REMAGUS02 trial, a cohort of 156 patients with human epidermal growth factor receptor 2–negative breast cancer with pretreatment PTGS2 expression data was analyzed.
• Treatment of patients was sequential NAC (epirubicin plus cyclophosphamide followed by docetaxel with or without celecoxib).
• Researchers performed experimental validation on breast cancer cell lines.
• Independent validation cohort comprised the Cancer and Leukemia Group B (CALGB) 30801 trial that tested chemotherapy with or without celecoxib in patients with lung cancer.

Results

• Significantly lower EFS was noted in the celecoxib group after 94.5 months of follow-up (hazard ratio [HR], 1.7; 95% CI, 1 to 2.88; P=.046).
• Findings suggest a significant interaction between PTGS2 expression and celecoxib use (P_interaction=.01).
• In the PTGS2-low group (n = 100), they observed lower EFS in the celecoxib arm (HR, 3.01; 95% CI, 1.45 to 6.24; P=.002) than in the standard treatment arm.
• Poor EFS, distant relapse–free survival, and OS were noted in independent association with celecoxib use.
• Enhanced cell viability was noted in PTGS2-low cell lines but not in PTGS2-high cell lines with celecoxib in addition to docetaxel.
• They observed a trend toward poorer progression-free survival in the patients with low urinary metabolite of prostaglandin E2 who received celecoxib in CALGB 30801(HR = 1.57; 95% CI, 0.87 to 2.84; P=.13).