TY - JOUR
T1 - Improved Survival With Adjuvant Cyclooxygenase 2 Inhibition in PIK3CA -Activated Stage III Colon Cancer
T2 - CALGB/SWOG 80702 (Alliance)
AU - Nowak, Jonathan A.
AU - Twombly, Tyler
AU - Ma, Chao
AU - Shi, Qian
AU - Haruki, Koichiro
AU - Fujiyoshi, Kenji
AU - Väyrynen, Juha
AU - Zhao, Melissa
AU - Knight, James
AU - Mane, Shrikant
AU - Shergill, Ardaman
AU - Kumar, Pankaj
AU - Couture, Felix
AU - Kuebler, Philip
AU - Krishnamurthi, Smitha
AU - Tan, Benjamin
AU - Philip, Philip
AU - O'Reilly, Eileen M.
AU - Shields, Anthony F.
AU - Ogino, Shuji
AU - Fuchs, Charles S.
AU - Meyerhardt, Jeffrey A.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2024/8/20
Y1 - 2024/8/20
N2 - 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 (Pinteraction =.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]; Pinteraction =.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.
AB - 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 (Pinteraction =.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]; Pinteraction =.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.
UR - http://www.scopus.com/inward/record.url?scp=85201438699&partnerID=8YFLogxK
U2 - 10.1200/JCO.23.01680
DO - 10.1200/JCO.23.01680
M3 - Article
C2 - 38889377
AN - SCOPUS:85201438699
SN - 0732-183X
VL - 42
SP - 2853
EP - 2859
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 24
ER -