Tailored COX-2 Inhibition for Precision Adjuvant Therapy of Localized Metastatic Colon Cancer
Menée auprès de 940 patients atteints d'un cancer colorectal de stade III et inclus dans un essai de phase III évaluant le célécoxib en traitement adjuvant, cette étude évalue l'intérêt de détecter la présence de l'ADN tumoral circulant après l'opération pour prédire la survie et identifier les patients nécessitant l'ajout de célécoxib à une chimiothérapie adjuvante conventionnelle
CALGB/SWOG 80702 Alliance was a placebo-controlled randomized clinical trial (RCT) of daily celecoxib (400 mg/d vs placebo) as an adjuvant therapy to fluorouracil, leucovorin, and oxaliplatin (FOLFOX) toward improving disease-free survival (DFS) of minimal residual localized (stage III) metastatic colon cancer. The rationale for the trial was a preponderance of evidence from RCTs and observational studies showing that selective cyclooxygenase 2 (COX-2 or prostaglandin-endoperoxide synthase 2 [PTGS2]) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) such as celecoxib and rofecoxib, reduce the incidence of premalignant colorectal polyps and colorectal cancer (CRC). Although the primary trial results did not show daily celecoxib to be statistically significantly associated with improvement in DFS or overall survival (OS), the results raised the possibility that yet-to-be-determined subgroups may experience a significant benefit. Indeed, Nowak et al reported in 2024 that a significant protective effect was observed among patients with tumors harboring mutations to exons 9 or 20 of the PIK3CA gene within the subset of the Alliance trial population with available whole-exome tumor sequencing data.
JAMA Oncology , éditorial, 2025