Low-dose aspirin reduces colorectal cancer recurrence for patients with PI3K mutations
Key takeaways:
- Low-dose aspirin reduced risk for colorectal cancer recurrence among patients who had mutations in the PI3K pathway.
- Researchers observed the association for people with PI3KCA and non-PI3KCA mutations.
Low-dose aspirin significantly reduced risk for colorectal cancer recurrence among patients with mutations in the PI3K pathway, according to results of the randomized ALASCCA study presented at ASCO Gastrointestinal Cancers Symposium.
Researchers observed the risk reduction among patients with PI3KCA mutations and those with non-PI3KCA mutations in the PI3K pathway.
“This is the first trial to show that mutations in this specific signal pathway beyond the PI3KCA predict aspirin response, expanding the [targetable] population to more than a third of the patients,” Anna Martling, MD, PhD, FACS (Hon), FASCRS (Hon), professor of surgery at Karolinska Institutet in Sweden, said during a press briefing. “This is an example of repurposing a safe, inexpensive and globally available drug, and it stresses the importance of upfront genomic testing [for people] with colorectal cancer.”
Background and methods
Approximately 1.9 million individuals around the world are diagnosed with colorectal cancer annually, according to study background.
Colorectal cancer incidence is increasing and it is projected to be the second leading cause of cancer mortality in the U.S. this year, according to American Cancer Society’s Cancer Statistics 2025 report.
Aspirin has been studied extensively for decades, and research has shown it may have an effect on colorectal cancer.
One study showed people taking aspirin for cardiovascular indications may be at lower risk for colorectal cancer, and another showed taking aspirin after colorectal cancer diagnosis may extend DFS.
“Moreover, two retrospective studies initially designed for other purposes indicated that this might be linked to PIK3CA mutations in the tumor,” Martling said. “This is the basis for ALASCCA study, which was designed to examine aspirin’s effect on colorectal cancer recurrence by using iterations in the PI3K pathway as a potential predictive genetic biomarker.”
Researchers screened 3,508 people with colorectal cancer from Sweden, Denmark, Finland and Norway for the trial, and 37% had mutations in the PI3K pathway.
The final analysis included 626 individuals (median age, 66 years; range, 31-80; 52% women; 67% with colon cancer).
Researchers divided study participants into two groups. Group A included 314 individuals with PIK3CA mutations. Group B included 312 patients with other mutations in the pathway.
Martling and colleagues randomly assigned 157 patients in group A and 156 in group B to receive 160 mg aspirin daily for 3 years. The other half of patients in each group received daily placebo for 3 years.
Time to colorectal cancer recurrence in group A served as the primary endpoint. Secondary endpoints included DFS in group A, time to recurrence and DFS in group B, and safety measures.
Results and next steps
In group A, patients assigned aspirin had significantly lower 3-year cumulative incidence of recurrence than those assigned placebo (7.7% vs. 14.1%; HR = 0.49; 95% CI, 0.24-0.98). They also had improved 3-year DFS (88.5% vs. 81.4%), though the difference did not reach statistical significance.
In group B, individuals assigned aspirin had significantly lower 3-year cumulative incidence of recurrence (7.7% vs. 16.8%; HR = 0.42; 95% CI, 0.21-0.83) and improved 3-year DFS (89.1% vs. 78.7%; HR = 0.51; 95% CI, 0.29-0.88).
Aspirin reduced risk for recurrence across all subgroups examined, including those based on cancer type, cancer stage, sex, and receipt of adjuvant or neoadjuvant therapy.
More individuals assigned aspirin experienced adverse events (301 vs. 228), severe adverse events (57 vs. 38) and severe adverse events that led to death (3 vs. 1).
Martling described incidence of severe adverse events as “rare.”
“I think it’s really clear that this is a practice-changing study,” ASCO expert Pamela L. Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, as well as chief of gastrointestinal medical oncology at Yale School of Medicine, said during the press briefing.
“It checks all of the boxes. It’s effective, it’s low risk, it’s inexpensive and it’s easy to administer. What we’re seeing in terms of [reductions in risk for recurrence] in both of these populations is really important, and I anticipate that we’ll be seeing the adoption of this. Aspirin as chemoprevention has been around for a while, but the uptake and the data to demonstrate its effectiveness has been lacking. This really changes that paradigm.”
Even though aspirin is inexpensive, Julie R. Gralow, MD, FACP, FASCO, ASCO chief medical officer and executive vice president, noted the high costs of genomic testing that may need to be used to guide its use.
Kunz acknowledged this but added payers should cover the costs because it ultimately may yield financial benefits.
“[Aspirin] reduces the risk [for] recurrence between 50% and 60% in both of those groups,” Kunz said. “I think we are saving in terms of the downstream costs associated with a recurrent cancer.”
Collapse
Martling A, et al. Abstract LBA125. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 23-25, 2025; San Francisco.