PIK3CA Could Guide Use of COX-2 Inhibitors in Treatment for Colon Cancer

Jun 28, 2024

THURSDAY, June 27, 2024 (HealthDay News) — PIK3CA mutational status may be beneficial for predicting response to addition of the cyclooxygenase 2 (COX-2) inhibitor celecoxib to standard adjuvant chemotherapy in stage III resected colon cancer, according to a study published online June 18 in the Journal of Clinical Oncology.

Jonathan A. Nowak, M.D., Ph.D., from Brigham and Women’s Hospital in Boston, and colleagues prospectively examined whether adding the COX-2 inhibitor celecoxib to standard adjuvant chemotherapy reduces the risk of recurrence and improves survival for patients with stage III resected colon cancer. Preplanned subgroup analysis was performed by PIK3CA mutational status. Of the 1,197 tumors with available whole-exome sequencing data, PIK3CA gain-of-function mutations were identified in 259.

The researchers found that there was no significant improvement in disease-free survival (DFS) with celecoxib for all patients. On stratification by PIK3CA status, patients with gain-of-function mutations treated with celecoxib had significantly improved DFS (adjusted hazard ratio, 0.56 [95 percent confidence interval, 0.33 to 0.96]) compared with wildtype PIK3CA patients (adjusted hazard ratio, 0.89 [0.70 to 1.14]); the interaction was not significant. Patients with PIK3CA gain-of-function mutations had similarly improved overall survival (adjusted hazard ratio, 0.44 [0.22 to 0.85]) compared with wildtype patients (adjusted hazard ratio, 0.94 [0.68 to 1.30]).

“These findings represent the first clinical trial results to validate observational studies that have associated adjuvant aspirin and other nonsteroidal anti-inflammatory drug use, including COX-2 inhibitors, with improved survival for patients with PIK3CA-mutant colorectal cancer,” the authors write.

Several authors disclosed ties to the biopharmaceutical industry.

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