According to one of the first biomarker-driven randomized study in people with nonmetastatic colorectal cancer, taking 160 mg of aspirin daily after treatment ends may reduce the risk of cancer recurrence in patients with cancers that harbor a PI3K mutation. These mutations are common to many types of cancer and are found in approximately 30% of colorectal cancers. This research was presented at the 2025 ASCO Gastrointestinal Cancers Symposium in San Francisco by Anna Martling, MD, PhD, Professor at Karolinska Institutet, Department of Molecular Medicine and Surgery, in Stockholm.
The ALASCCA Study
The ALASCCA trial was a randomized, double-blind, multicenter, placebo-controlled trial with 3,508 patients across 33 hospitals in Sweden, Denmark, Finland, and Norway screened for this trial. They either had stage II or III colon cancer or stage I, II, or III rectal cancer. The median patient age was 66 years, and 52% were women. Most patients were White.
Of those patients, 1,103 had a genetic change in the PI3K pathway. These patients were then divided into two groups for treatment in the clinical trial: Group A included patients with a PIK3CA mutation in exon 9 and/or 20. Group B included patients with other PI3K mutations, including PIK3CA mutations outside exon 9/20 or mutations in PIK3R1 or PTEN genes.
Ultimately, 626 patients continued on with the trial and received treatment. Of those patients, 419 had colon cancer, and 207 had rectal cancer. Patients in groups A and B were randomly assigned to receive 160 mg of daily aspirin or a placebo for 3 years.
Key Findings
When compared with placebo, patients in both groups were less likely to have their cancer grow or change over 3 years if they took aspirin. Patients in group A had a 51% lower risk of cancer recurrence when compared with placebo. The rate of recurrence in this group was 7.7% in patients who took aspirin and 14.1% for those who took a placebo. Patients in group B had a 58% lower risk of cancer recurrence when compared with placebo. The rate of recurrence in this group was 7.7% in patients who took aspirin and 16.8% in patients who took a placebo.
The benefit of using aspirin was seen for all groups, no matter what type of driver alteration or change to the PI3K pathway they had. For groups A and B combined, patients who took aspirin were 55% less likely to have their cancer recur than those who took a placebo.
According to the authors, the results of this study could immediately change practice for a significant portion of patients diagnosed with colorectal cancer. “We have studied and demonstrated the value of a widely used, well-established, and cost-effective drug with a low-risk profile for patients with colorectal cancer. Aspirin has been shown to effectively reduce recurrence rates and improve disease-free survival in more than one-third of these patients,” said Dr. Martling, the lead study author. She added: “In addition, this research highlights the importance of precision medicine and the use of advanced diagnostics. These tools can enable tailored treatments and the repurposing of existing drugs for new applications.”
Severe side effects of daily low-dose aspirin use were rare. There was one case of severe gastrointestinal bleeding, one case of brain bleeding, and one allergic reaction.
Researchers will continue to study the data collected during this trial with additional subgroup analyses planned, including the role of sex and socioeconomic status.
ASCO Perspective
“The old adage ‘take two aspirin and call me in the morning’ may now find a new meaning. A simple intervention of low-dose aspirin reduces the risk of colorectal cancer recurrence for patients with genetic changes in the PI3K signaling pathway, occurring in one-third of patients with colorectal cancer,” said ASCO Expert, Pamela L. Kunz, MD, of Yale School of Medicine.
Disclosure: This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Dr. Kunz reported a consulting or advisory role with Bristol Myers Squibb and Foundation Medicine. For full disclosures of all study authors, visit ASCO.org.