Does adjuvant aspirin have a protective effect in resected PIK3CA-mutant colon cancer?

Adjuvant aspirin is associated with clinically relevant disease-free survival (DFS) and time to disease recurrence (TTR) improvements in resected PIK3CA-mutant colon cancer, according to a phase III randomized, placebo-controlled trial.

Previously, a prospective cohort study has provided evidence for a protective effect of adjuvant aspirin in patients with PIK3CA-mutant colorectal cancer (CRC). [N Engl J Med 2012;367:1596-1606] “The objective of study SAKK 41/13 – the first one in the literature – [was] to investigate the benefit of adjuvant aspirin in selected PIK3CA-mutant colon cancer patients in a randomized controlled setting,” wrote the researchers. [Clin Cancer Res 2025;31:3142-3149]

The phase III, prospective, randomized, placebo-controlled, double-blind, multicentre, multinational SAKK 41/13 trial randomized 112 patients with resected PIK3CA-mutant stage II or III colon cancer to receive either aspirin 100 mg QD (n=74; mean age, 68 years; male, 59.5 percent) or placebo (n=38; mean age, 65 years; male, 52.6 percent) between April 2016 and November 2020. Adjuvant chemotherapy was given to 70.3 percent of patients in the aspirin group and 63.2 percent of patients in the placebo group.

The trial was prematurely closed due to financial constraints. Median treatment duration was 22.1 months in the aspirin arm and 21.6 months in the placebo arm. Compliance with aspirin and placebo intake was high: the median number of pills taken per patient per day was 1 in both arms.

Median DFS was not reached in both arms. The stratified hazard ratio (HR) for DFS was 0.57 (90 percent confidence interval [CI], 0.22–1.46) in favour of aspirin. DFS rates at 3 years were 88.3 percent in the aspirin arm and 82.4 percent in the placebo arm. The respective rates at 5 years were 86.5 and 72.9 percent.

The overall recurrence rates were 9.5 and 18.4 percent in the aspirin and placebo arms, respectively, while rates of isolated distant recurrences were 6.8 and 10.5 percent. At 0.56 (90 percent CI, 0.20–1.55), the stratified HR for TTR was similar to DFS, in favour of aspirin. The stratified HR for overall survival was 0.60 (90 percent CI, 0. 15–2.43), again, in favour of aspirin.

While none of the findings reached statistical significance, the researchers noted that the sample size was small and the trial was underpowered due to premature closure. “The 43 percent relative reduction and the absolute DFS reduction of >13 percent at 5 years are clinically relevant,” they stressed.

The study treatment was well tolerated, with grade 3 treatment-emergent adverse events (AEs) occurring in one patient in the aspirin group and three patients in the placebo group. No aspirin-related serious AEs were reported. “The extremely good side effect profile and very low financial toxicity make aspirin an attractive adjuvant treatment,” remarked the researchers.

“Although the results were not statistically significant due to premature study closure, adjuvant aspirin warrants individual consideration in patients with resected stage II or III PIK3CA-mutant colon cancer,” they concluded.