In an analysis from the CALGB/SWOG 80702 (Alliance) trial published by Nowak et al in the Journal of Clinical Oncology, researchers found that the addition of the cyclooxygenase 2 (COX-2) inhibitor celecoxib to standard adjuvant chemotherapy was associated with improved disease-free survival and overall survival in a subgroup of patients with stage III colon cancer and PIK3CA gain-of-function mutations.
Study Details
In the U.S. multicenter trial, 2,526 patients were randomly assigned in a 2 x 2 design between June 2010 and November 2015 to receive FOLFOX (fluorouracil, leucovorin, and oxaliplatin) for 3 or 6 months and either celecoxib at 400 mg or placebo once daily for 3 years. In the primary analysis, the addition of celecoxib to chemotherapy did not significantly improve disease-free survival; 3-year rates were 76.3% vs 73.4% (hazard ratio [HR] = 0.89, 95% confidence interval [CI] = 0.76–1.03, P = .12).
PIK3CA gain-of-function mutations were detected in 259 of 1,197 patients with available whole-exome sequencing data, including 141 in the celecoxib group vs 118 in the control group; wild-type PIK3CA was found in 450 vs 488 patients.
Key Findings
Among patients with PIK3CA gain-of-function mutations, those in the celecoxib group showed improved disease-free survival vs those in the control group (adjusted HR = 0.56, 95% CI = 0.33–0.96); among PIK3CA wild-type patients, the adjusted hazard ratio was 0.89 (95% CI = 0.70–1.14), with the test for heterogeneity being nonsignificant (P for interaction = .13).
Among patients with PIK3CA gain-of-function mutations, those in the celecoxib group showed improved overall survival vs those in the control group (adjusted HR = 0.44, 95% CI = 0.22–0.85); among PIK3CA wild-type patients, the adjusted hazard ratio was 0.94 (95% CI = 0.68–1.30), with a significant test for heterogeneity (P for interaction = .04).
The investigators concluded, “Although the test for heterogeneity in disease-free survival did not reach statistical significance, the results suggest potential utility of PIK3CA to consider selective usage of COX-2 inhibitors in addition to standard treatment for stage III colon cancer.”
Jonathan A. Nowak, MD, PhD, of Brigham and Women’s Hospital and Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and others. For full disclosures of the study authors, visit ascopubs.org.
