Aspirin Reduces Colorectal Cancer Recurrence in High-Risk Patients

Strategic Insights -

Researchers from the Karolinska Institute in Stockholm, Sweden, have conducted a landmark study on the efficacy of low-dose aspirin in reducing colorectal cancer recurrence in high-risk patients. The study's findings, published in the New England Journal of Medicine, reveal that aspirin significantly lowers the incidence of colorectal cancer recurrence among patients with specific genetic mutations.

The double-blind, randomized, placebo-controlled trial involved 622 patients with stage I, II, or III rectal cancer or stage II or III colon cancer. Participants were randomly assigned to receive either 160 mg of aspirin or a matched placebo once daily for three years. The results showed that patients with PIK3CA hotspot mutations in exon 9 or 20 experienced a significantly lower incidence of colorectal cancer recurrence when taking aspirin, with a hazard ratio of 0.49 (95% CI, 0.24 to 0.98; P = 0.04). Patients with other somatic alterations in PI3K pathway genes also benefited from aspirin, with a hazard ratio of 0.42 (95% CI, 0.21 to 0.83).

Key Takeaways:

  • The study found that aspirin significantly reduced colorectal cancer recurrence among patients with PIK3CA hotspot mutations in exon 9 or 20 (hazard ratio, 0.49; 95% CI, 0.24 to 0.98; P = 0.04).
  • Patients with other somatic alterations in PI3K pathway genes also benefited from aspirin, with a hazard ratio of 0.42 (95% CI, 0.21 to 0.83).
  • The estimated 3-year disease-free survival was 88.5% with aspirin and 81.4% with placebo (hazard ratio, 0.61; 95% CI, 0.34 to 1.08) among patients with group A alterations and 89.1% and 78.7%, respectively (hazard ratio, 0.51; 95% CI, 0.29 to 0.88), among those with group B alterations.
  • Severe adverse events occurred in 16.8% of aspirin recipients and 11.6% of placebo recipients.
  • The study suggested that aspirin may improve disease-free survival particularly among patients with tumors harboring somatic PIK3CA mutations.

Statistics:

  • 622 patients participated in the trial.
  • 314 patients with PIK3CA hotspot mutations in exon 9 or 20 were assigned to receive aspirin or placebo.
  • 588 patients with other somatic alterations in PI3K pathway genes were assigned to receive aspirin or placebo.
  • 7.7% of patients with group A alterations experienced colorectal cancer recurrence with aspirin, compared to 14.1% with placebo.
  • 7.7% of patients with group B alterations experienced colorectal cancer recurrence with aspirin, compared to 16.8% with placebo.
  • 88.5% of patients with group A alterations achieved 3-year disease-free survival with aspirin, compared to 81.4% with placebo.
  • 89.1% of patients with group B alterations achieved 3-year disease-free survival with aspirin, compared to 78.7% with placebo.

Sources:

  • New England Journal of Medicine, Low-dose Aspirin for Pi3k-altered Localized Colorectal Cancer, 393(11), 1051-1064, 2025.
  • NewsRx, New Findings from Karolinska Institute in the Area of Disease-Free Survival Described (Low-dose Aspirin for Pi3k-altered Localized Colorectal Cancer), Cancer Weekly, October 21, 2025, p 1699.