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Improved Survival With Adjuvant Cyclooxygenase 2 Inhibition in PIK3CA -Activated Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Aug 20; Vol. 42 (24), pp. 2853-2859. Date of Electronic Publication: 2024 Jun 18. - Publication Year :
- 2024
-
Abstract
- Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Observational studies have associated aspirin or cyclooxygenase 2 (COX-2) inhibitor usage either before or after colorectal cancer diagnosis with lower risk of recurrence and suggest that PIK3CA mutational status is predictive of better response to COX-2 inhibition. To prospectively test whether adding the COX-2 inhibitor celecoxib to standard adjuvant chemotherapy reduces the risk of recurrence and improves survival, the National Cancer Institute sponsored the CALGB/SWOG 80702 trial (ClinicalTrials.gov identifier: NCT01150045) for patients with stage III resected colon cancer. Although the primary hypothesis for all patients did not show a statistically significant improvement in disease-free survival (DFS) with celecoxib, subgroup analysis by PIK3CA mutational status was a preplanned study. PIK3CA gain-of-function mutations were detected in 259 of 1,197 tumors with available whole-exome sequencing data. When stratified by PIK3CA status, patients with PIK3CA gain-of-function mutations treated with celecoxib exhibited improved DFS (adjusted hazard ratio [HR], 0.56 [95% CI, 0.33 to 0.96]) compared with PIK3CA wildtype patients (adjusted HR, 0.89 [95% CI, 0.70 to 1.14]), although the interaction test was nonsignificant ( P <subscript>interaction</subscript> = .13). Overall survival was similarly improved for patients with PIK3CA gain-of-function mutations (adjusted HR, 0.44 [95% CI, 0.22 to 0.85]) compared with PIK3CA wildtype patients (adjusted HR, 0.94 [95% CI, 0.68 to 1.30]; P <subscript>interaction</subscript> = .04). Although the test for heterogeneity in DFS 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.
- Subjects :
- Humans
Male
Female
Chemotherapy, Adjuvant
Aged
Middle Aged
Mutation
Disease-Free Survival
Prospective Studies
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Adult
Class I Phosphatidylinositol 3-Kinases genetics
Cyclooxygenase 2 Inhibitors therapeutic use
Cyclooxygenase 2 Inhibitors pharmacology
Colonic Neoplasms drug therapy
Colonic Neoplasms genetics
Colonic Neoplasms mortality
Colonic Neoplasms pathology
Neoplasm Staging
Celecoxib therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 42
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 38889377
- Full Text :
- https://doi.org/10.1200/JCO.23.01680