Low-Dose Aspirin Reduces the Risk of Recurrence in Colorectal Cancer with PI3K Mutations
Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer
New England Journal of Medicine — Sept 17, 2025 • ALASCCA RCT • ClinicalTrials.gov: NCT02647099
Primary Outcome
3-yr recurrence (PIK3CA exon 9/20):
7.7%
Aspirin
14.1%
Placebo
HR 0.49 (95% CI 0.24–0.98), p=0.04
Key Secondary
3-yr recurrence (other PI3K/PTEN):
7.7%
Aspirin
16.8%
Placebo
HR 0.42 (95% CI 0.21–0.83)
Who & How
- Stage I–III rectum or II–III colon
- Somatic PI3K-pathway alteration
- 160 mg daily for 3 years
- Double-blind, placebo-controlled
Disease-Free Survival (3-yr)
PIK3CA exon 9/20
88.5%
Aspirin
81.4%
Placebo
HR 0.61 (0.34–1.08)
Other PI3K/PTEN
89.1%
Aspirin
78.7%
Placebo
HR 0.51 (0.29–0.88)
Lower HR <1 favors aspirin.
Safety Snapshot
16.8%
Severe AEs (aspirin)
11.6%
Severe AEs (placebo)
- Bleeding/GI events remain key monitoring focus.
- Use shared decision-making; weigh benefit vs risk.
Design & Population
- Double-blind, randomized, placebo-controlled (1:1)
- PI3K-pathway alterations found in 37.0% (1103/2980) with complete genomics
- Randomized: Group A (PIK3CA exon 9/20 hotspots) n=314; Group B (other PI3K/PTEN) n=312
- Intervention: Aspirin 160 mg once daily × 3 years
Take-Home
- Aspirin significantly reduces recurrence in PI3K-altered CRC.
- Benefit observed across hotspot and other PI3K/PTEN variants.
- Safety profile requires bleeding vigilance.
Reference: Martling A, Myrberg IH, Nilbert M, Grönberg H, Granath F, Eklund M, Öresland T, et al. Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer. New England Journal of Medicine. 2025;393:1051–1064. DOI: 10.1056/NEJMoa2504650.
