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ALASCCA

A Nordic trial showing that three years of low-dose aspirin roughly halves recurrence in bowel cancers carrying a particular set of mutations, a biomarker-directed use of a drug that costs pennies.

3,508 patients were screened for tumour PIK3CA and PI3K-pathway alterations; 626 with alterations were randomised. In group A (PIK3CA exon 9 or 20 hotspot mutations, n=314) recurrence at three years was 7.7% with aspirin vs 14.1% with placebo (HR 0.49, 95% CI 0.24-0.98); in group B (other PIK3CA mutations or PIK3R1/PTEN alterations, n=312) it was 7.7% vs 16.8% (HR 0.42, 95% CI 0.21-0.83). Severe adverse events attributable to aspirin were uncommon (about 2%). ALASCCA validates a decade of observational data from the Nurses' Health Study and CALGB 89803 suggesting PIK3CA-mutant tumours are aspirin-sensitive, and creates an implementation task: routine PIK3CA testing in early colorectal cancer, which most pathology services do not currently perform.

Setting
Resected stage I-III rectal or stage II-III colon cancer with somatic PIK3CA (exon 9/20) or other PI3K-pathway alterations: aspirin 160 mg/day for 3 years vs placebo
Phase
Phase 3
Sponsor
Karolinska Institutet
Registry
Headline result
3-year recurrence HR 0.49 (PIK3CA hotspot) and 0.42 (other PI3K alterations).
Reported
2025
Enrolled
626
Replication
Awaits confirmation; the ADD-ASPIRIN trial includes a pre-planned PIK3CA analysis. Observational cohorts are concordant.

Outcomes

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In plain words
What these results mean for people, not percentages
626 people took part
Time to recurrence at 3 years, group A (PIK3CA exon 9/20)primarysurrogate endpoint
  • 7.7 vs 14.1 out of 100 reached this endpoint at 3 years with Aspirin compared with Placebo; 6.4 fewer per 100.
  • On this measure the first group did worse, not better.
  • Put another way, the treated group had about 51 percent lower chance of the event at any given time (hazard ratio 0.49, likely range 0.24 to 0.98).
Time to recurrence at 3 years, group B (other PI3K-pathway alterations)surrogate endpoint
  • 7.7 vs 16.8 out of 100 reached this endpoint at 3 years with Aspirin compared with Placebo; 9.1 fewer per 100.
  • On this measure the first group did worse, not better.
  • Put another way, the treated group had about 58 percent lower chance of the event at any given time (hazard ratio 0.42, likely range 0.21 to 0.83).
Be careful
  • This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
  • These results apply to the people the trial enrolled: Resected stage I-III rectal or stage II-III colon cancer with somatic PIK3CA (exon 9/20) or other PI3K-pathway alterations: aspirin 160 mg/day for 3 years vs placebo. People in a different situation may not see the same effect.
  • The trial selected people by a biomarker (PIK3CA); the result should not be assumed for people whose cancer does not have it.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

626 participants enrolled.

Time to recurrence at 3 years, group A (PIK3CA exon 9/20)primary
HR 0.49 (0.24–0.98)
Aspirin7.7 of 100
Placebo14.1 of 100
Source
Time to recurrence at 3 years, group B (other PI3K-pathway alterations)
HR 0.42 (0.21–0.83)
Aspirin7.7 of 100
Placebo16.8 of 100
Source
EndpointArmnValueHR (95% CI)pSource
Time to recurrence at 3 years, group A (PIK3CA exon 9/20)primaryAspirin7.7%0.49 (0.24–0.98)link
Placebo14.1%
Time to recurrence at 3 years, group B (other PI3K-pathway alterations)Aspirin7.7%0.42 (0.21–0.83)link
Placebo16.8%
Replication
Awaits confirmation; the ADD-ASPIRIN trial includes a pre-planned PIK3CA analysis. Observational cohorts are concordant.

Connected

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