N Engl J Med

Low-dose aspirin reduces recurrence in PI3K-altered localized colorectal cancer

September 23, 2025

Low-dose aspirin significantly reduces recurrence in patients with localized colorectal cancer harboring PI3K pathway alterations, supporting molecular stratification for adjuvant therapy decisions. Routine assessment of PI3K status may guide aspirin use in this setting, though increased adverse events warrant careful risk-benefit evaluation.

Study details: The double-blind, randomized, placebo-controlled ALASCCA trial (NCT02647099) enrolled patients with resected stage I–III rectal or stage II–III colon cancer harboring somatic PI3K pathway gene alterations (PIK3CA, PIK3R1, or PTEN). Patients with prespecified PIK3CA hotspot mutations in exon 9 or 20 (group A alterations) and those with other moderate- or high-impact somatic variants in PIK3CA, PIK3R1, or PTEN (group B alterations) were eligible for randomization. Participants (n = 626) were randomized 1:1 to receive 160 mg aspirin or placebo daily for 3 years. Primary endpoint was colorectal cancer recurrence in patients with group A alterations; secondary endpoints included recurrence in patients with group B alterations, disease-free survival, and safety.

Results: In group A, the 3-year cumulative incidence of recurrence was 7.7% with aspirin vs. 14.1% with placebo (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.24–0.98; P=0.04). In group B, recurrence was 7.7% vs. 16.8% (HR, 0.42; 95% CI, 0.21–0.83). Disease-free survival at 3 years was higher with aspirin in both groups. Severe adverse events were more frequent with aspirin (16.8% vs. 11.6%).

Source:

Martling A; ALASCCA Study Group, et al. (2025, September 18). N Engl J Med. Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer. https://pubmed.ncbi.nlm.nih.gov/40961426/