Aspirin Does Not Limit Recurrence, Improve Survival in CRC Liver Metastases

Aspirin led to a median disease-free survival of 1.16 years vs 1.35 years with placebo in patients with colorectal cancer liver metastases.

Adjuvant aspirin did not reduce the rate of recurrence nor improve survival outcomes for patients with colorectal cancer (CRC) liver metastases and cannot be recommended as an adjuvant treatment, according to results from the randomized phase 3 ASAC trial (NCT03326791).1 These findings were shared at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

The median disease-free survival (DFS) with aspirin was 1.16 years (95% CI, 0.86-1.51) vs 1.35 years (95% CI, 0.92-1.98) with placebo; the 3-year DFS hazard ratio was 1.06 (95% CI, 0.77-1.45; P = .64). Among those who received aspirin, 217 patients were at risk at 0 years, 106 patients at 1 year, 72 at 2 years, and 40 at 3 years; of those who received placebo, 211 patients were at risk at 0 years, 108 at 1 year, 83 at 2 years, and 40 at 3 years.

Regarding overall survival, the probability of surviving beyond 36 months was 76.1% with aspirin vs 84.9% with placebo (HR, 1.60; 95% CI, 0.99-2.61; P = .057). Of those who received aspirin, 217 patients were at risk at 0 years; 186 patients at 1 year, 154 at 2 years, and 60 at 3 years; among those who received placebo, 211 patients were at risk at 0 years, 180 at 1 year, 160 at 2 years, and 71 at 3 years.

“Adjuvant aspirin [at 160 mg] does not reduce the recurrence rate in patients with [CRC] liver metastases,” stated presenting study author Sheraz Yaqub, MD, PhD,senior consultant surgeon and associate professor of surgery in the Department of Gastroenterological Surgery at Oslo University Hospital in Oslo, Norway, in the presentation.1 “The protective effect of aspirin in [CRC] is not transferrable to metastatic disease. Aspirin cannot be recommended as adjuvant treatment for [CRC] liver metastases.”

The ASAC trial enrolled a total of 466 patients who were randomly assigned, in a 1:1 ratio, to receive either 160 mg of aspirin daily for 3 years (n = 234) or placebo daily for 3 years (n = 232). Eligible patients had CRC liver metastases eligible for radical treatment of resection or ablation. Those with ongoing use of aspirin or other anti-platelet or anti-coagulant agents were excluded from participation.

The mean age of patients was 62 years (SD, 10.98), 64% were male and 36% were female, 66% had colon cancer and 34% had rectal cancer, and 45% had synchronous liver metastases while on aspirin compared with 42% on placebo.

The trial’s primary end point was 3-year DFS. Secondary end points included 3-year OS, safety, time to recurrence, quality of life, and health economics.

Regarding safety, adverse events (AEs) occurred in 85% of those receiving aspirin and 76% receiving placebo, serious AEs occurred in 24% and 5%, and life-threatening serious AEs occurred in 4% and 1%. Serious AEs led to death in 1% of those who received aspirin.

Clinically relevant AEs and serious AEs in the aspirin group were epistaxis (n = 4), abdominal pain (n = 3), myocardial infection (n = 2), duodenal ulcer (n = 2), and cerebral hemorrhage (n = 2); in the placebo group, they were abdominal pain (n = 4) and cerebral stroke (n = 2).

It was noted that in the phase 3 ALASCCA trial (NCT02647099), aspirin did demonstrate improved DFS in patients with non-metastatic CRC harboring PIK3CA mutations (HR, 0.51; 95% CI, 0.29-0.88; P = .017).2

References

1. Yaqub S, Bjørnbeth BA, Angelsen J, et al. Aspirin as secondary prevention for colorectal cancer liver metastases (ASAC): a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. J Clin Oncol. 2025;43(suppl 17):3511. doi:10.1200/JCO.2025.43.17_suppl.LBA3511
2. Martling A, Lindberg J, Myrberg IH, et al. Low-dose aspirin to reduce recurrence rate in colorectal cancer patients with PI3K pathway alterations: 3-year results from a randomized placebo-controlled trial. J Clin Oncol. 2025;43(4):LBA125. doi:10.1200/JCO.2025.43.4_suppl.LBA125