Clinical trialPhase 3Colorectal cancer

Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer

N Engl J Med · 2025626 randomised patients (314 in group A and 312 in group B)

Martling A, Hed Myrberg I, Nilbert M, Grönberg H, Granath F, Eklund M, et al. N Engl J Med. 2025. 393:1051-1064

Study type: Clinical trial
Study name: ALASCCA
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial, 1:1 ratio
Sample size: 626 randomised patients (314 in group A and 312 in group B)
Source: N Engl J Med · 2025
Trial registration: NCT02647099

In plain words

In people with bowel cancer whose tumour had a particular genetic change in the PI3K pathway, taking one low-dose aspirin tablet every day for 3 years roughly halved the risk of the cancer coming back. To use this finding, the tumour first needs a genetic test, and the decision should be made with your doctor.

Key results

7.7% vs 14.1%

3-year recurrence – group A

HR 0.49 (95% CI 0.24–0.98); P=0.04

7.7% vs 16.8%

3-year recurrence – group B

HR 0.42 (95% CI 0.21–0.83)

88.5% vs 81.4%

3-year disease-free survival – group A

HR 0.61 (95% CI 0.34–1.08)

89.1% vs 78.7%

3-year disease-free survival – group B

HR 0.51 (95% CI 0.29–0.88)

Dose and schedule cards

Low-dose adjuvant aspirin

Stage I to III rectal cancer or stage II to III colon cancer after radical surgery, with somatic PI3K pathway alterations (PIK3CA, PIK3R1 or PTEN); off-label useCycle length: Daily, continuousOn the page “Low-dose aspirin halved bowel cancer recurrence in patients with PI3K mutations” · ALASCCA trial regimen

Stage I to III rectal cancer or stage II to III colon cancer after radical surgery, with somatic PI3K pathway alterations (PIK3CA, PIK3R1 or PTEN); off-label use

Drug	Dose	Route	Schedule
Aspirin (acetylsalicylic acid)	160 mg	Oral	Once daily

Cycle length: Daily, continuous
Duration: 3 years

Key protocol criteria: platelets 100×10⁹/L or higher; a clear colonoscopy or CT colonography within 3 months before or after surgery. Exclusion criteria: Lynch syndrome or familial polyposis, a bleeding disorder, concomitant antiplatelet or anticoagulant use (postoperative low-molecular-weight heparin must be stopped before starting), active gastritis or peptic ulcer or significant postoperative bleeding in the past 3 months, regular corticosteroid or NSAID use, aspirin allergy, pregnancy or breastfeeding.

On the page “Low-dose aspirin halved bowel cancer recurrence in patients with PI3K mutations” · ALASCCA trial regimen

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Aspirin

Aspirin 160 mg orally once daily for 3 years.

2Placebo

Matching placebo once daily for 3 years.

Source of the regimen details: Abstract of the published paper (NEJM 2025)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with stage I, II or III rectal cancer or stage II or III colon cancer with somatic alterations in PI3K pathway genes. Group A: predefined PIK3CA hotspot mutations in exon 9 or 20. Group B: other somatic variants of moderate or high impact in PIK3CA, PIK3R1 or PTEN.

Endpoints

Primary endpoint: colorectal cancer recurrence (time-to-event analysis) in group A patients. Secondary endpoints: recurrence in group B, disease-free survival and safety.

Safety and side effects

Severe adverse events occurred in 16.8% of aspirin recipients and 11.6% of placebo recipients.

Clinical significance and place in guidelines

The first randomised trial to confirm adjuvant aspirin with biomarker-based selection (PI3K pathway alterations) in non-metastatic colorectal cancer; it has prompted discussion about adding PIK3CA/PTEN testing to routine tumour testing and its inclusion in consensus recommendations.

Limitations

Few events and wide confidence intervals; disease-free survival in group A was not significant; overall survival data immature; Northern European population.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.