In a Scandinavian trial (ALASCCA) reported in The New England Journal of Medicine, Martling et al found that low-dose aspirin reduced the risk of disease recurrence vs placebo in patients with PI3K-altered localized colorectal cancer.
Study Details
In the double-blind trial, patients with stage I to III rectal cancer or stage II to III colon cancer with somatic alterations in PI3K pathway genes were enrolled from sites in Sweden, Norway, Denmark, and Finland. A total of 314 patients with prespecified PIK3CA hotspot mutations in exon 9 or 20 (group A alterations) and a total of 312 with other moderate- or high-impact somatic variants in PIK3CA, PIK3R1, or PTEN (group B alterations) were randomly assigned to either receive aspirin at 160 mg (n = 157 group A, n = 156 group B) or placebo (157, 156) once daily for 3 years.
The primary endpoint of the study was colorectal cancer recurrence among patients with group A alterations.
Key Findings
Among patients with group A alterations, the estimated 3-year cumulative incidence of recurrence was 7.7% (95% confidence interval [CI] = 4.2%–12.5%) in the aspirin group vs 14.1% (95% CI = 9.2%–20.0%) in the placebo group (hazard ratio [HR] = 0.49, 95% CI = 0.24–0.98, P = .04). Among patients with group B alterations, the estimated 3-year cumulative incidence of recurrence was 7.7% (95% CI = 4.2%–12.6%) in the aspirin group vs 16.8% (95% CI = 11.4%–23.1%) in the placebo group (HR = 0.42, 95% CI = 0.21–0.83).
Estimated 3-year disease-free survival was 88.5% in the aspirin group vs 81.4% in the placebo group (HR = 0.61, 95% CI = 0.34–1.08) among patients with group A alterations and 89.1% vs 78.7% (HR = 0.51, 95% CI = 0.29–0.88) among those with group B alterations.
Nonsevere adverse events of any cause occurred in 43.4% of patients who received aspirin vs 35.4% of those who received placebo. Severe adverse events occurred in 16.8% of aspirin recipients vs 11.6% of placebo recipients; the most common in both groups were gastrointestinal disorders (6.5% vs 3.9%) and cardiovascular disorders (5.8% vs 4.2%).
The investigators concluded: “Aspirin led to a significantly lower incidence of colorectal cancer recurrence than placebo among patients with PIK3CA hotspot mutations in exon 9 or 20 and appeared to have a similar benefit among those with other somatic alterations in PI3K pathway genes.”
Anna Martling, MD, PhD, of the Department of Molecular Medicine and Surgery, Karolinska Institutet, Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden, is the corresponding author for the New England Journal of Medicine article.
Disclosure: The study was funded by the Swedish Research Council and others. For full disclosures of all study authors, visit nejm.org.
