PIK3CA May Guide COX-2 Inhibitors in Colon Cancer Treatment

On THURSDAY, June 27, 2024, researchers highlighted the potential predictive value of PIK3CA mutational status in determining the efficacy of adding the cyclooxygenase 2 (COX-2) inhibitor celecoxib to standard adjuvant chemotherapy for patients with stage III resected colon cancer. This information comes from a study published online on June 18 in the Journal of Clinical Oncology.

The research, led by Dr. Jonathan A. Nowak of Brigham and Women's Hospital in Boston, investigated whether incorporating the COX-2 inhibitor celecoxib with standard chemotherapy could reduce cancer recurrence risk and boost survival rates in patients who had undergone surgery for stage III colon cancer. The study included a preplanned subgroup analysis based on the presence of PIK3CA mutations. Out of 1,197 tumors analyzed using whole-exome sequencing, 259 exhibited PIK3CA gain-of-function mutations.

The study findings revealed no significant improvement in disease-free survival (DFS) when celecoxib was added for all patients collectively. However, when patients were segmented by their PIK3CA mutation status, a notable difference emerged. Those with PIK3CA gain-of-function mutations who received celecoxib showed significantly better DFS compared to those with the wildtype PIK3CA. The adjusted hazard ratio for these patients was 0.56 (with a 95 percent confidence interval ranging from 0.33 to 0.96), in contrast to wildtype patients who had an adjusted hazard ratio of 0.89 (with a confidence interval between 0.70 and 1.14). Although the interaction was not statistically significant, the trend suggested a beneficial effect of celecoxib for patients with PIK3CA mutations.

Additionally, overall survival rates also favored patients with PIK3CA gain-of-function mutations who were treated with celecoxib. Their adjusted hazard ratio for overall survival was 0.44 (confidence interval from 0.22 to 0.85), whereas the wildtype group had an adjusted hazard ratio of 0.94 (confidence interval from 0.68 to 1.30).

The authors of the study emphasized that these results represent the first clinical trial evidence supporting the findings of previous observational studies. These earlier studies had indicated that adjuvant aspirin and other nonsteroidal anti-inflammatory drugs, including COX-2 inhibitors, could improve survival for colorectal cancer patients with PIK3CA mutations.

It was also disclosed that several authors of the study have connections to the biopharmaceutical industry, although specific details of these ties were not elaborated within the article.