Adjuvant aspirin and Cyclooxygenase-2 inhibitors in resected, PIK3CA-mutated colorectal cancer: A systematic review and meta-analysis of randomized controlled trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 41621633 · doi:10.1016/j.critrevonc.2026.105167
What was done
PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) evaluating adjuvant nonsteroidal anti-inflammatory drugs (NSAIDs; aspirin or COX-2 inhibitors) versus placebo following curative-intent resection in patients with confirmed *PIK3CA*-mutated colorectal cancer (CRC). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for disease-free survival (DFS) and overall survival (OS) using fixed- and random-effects models. Sensitivity analyses excluded participants with concomitant low-dose aspirin and COX-2 inhibitor exposure.
What was found
Four RCTs met eligibility criteria, including 426 patients assigned to NSAIDs and 363 to placebo (total N = 789). - Adjuvant NSAID therapy improved DFS (HR 0.65; 95% CI, 0.46–0.90). - Sensitivity analysis excluding concomitant aspirin exposure showed HR 0.57 (95% CI, 0.39–0.83) for DFS. - Pooled OS was not statistically significant (HR 0.78; 95% CI, 0.39–1.57). - Sensitivity analysis excluding low-dose aspirin users was associated with lower mortality risk (HR 0.54; 95% CI, 0.30–0.99).
Why it matters
This review synthesizes randomized evidence indicating that *PIK3CA* mutation status may serve as a predictive biomarker for disease-free survival benefit from adjuvant NSAID therapy in resected colorectal cancer.
Limits
The total sample size is small (4 RCTs, 789 patients), resulting in an imprecise overall survival estimate. Aspirin and COX-2 inhibitors were pooled despite differing pharmacological profiles. Overall survival benefit was only observed in exploratory sensitivity analysis, and the abstract does not report safety, toxicity, or specific *PIK3CA* mutation exon subtypes.