Sheraz Yaqub, MD, PhD, Oslo University Hospital, Norway, shares insights from the phase 3 ASAC trial evaluating aspirin as secondary prevention of colorectal cancer liver metastases. The results found that daily aspirin after complete tumor removal did not improve the disease-free or overall survival of patients with colorectal cancer liver metastases. 

Dr Yaqub concluded, “As a whole, we can say that patients with colorectal cancer liver metastases do not benefit from having aspirin as adjuvant [treatment],” he also noted patients in the aspirin arm “had more severe adverse events and more adverse events, so it could be actually harmful to give them aspirin, especially if it doesn't give any better outcome.”

These data were first presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

Transcript:

Hi, my name is Sheraz Yaqub. I'm a hepatobiliary surgeon from Oslo University Hospital in Norway and also associate professor at the Institute of Clinic Medicine at the University of Oslo.

We've been running this ASAC trial, which is aspirin for colorectal liver metastasis. There has been a lot of interest during the last decades for the role of aspirin in the prevention of cancer and especially colorectal cancer. And there are loads of data from registry-based studies showing that aspirin can prevent cancer and also prevent recurrence after surgery for cancer, colorectal cancer.

This all started actually in the lab, 20 years ago, when we checked and mapped the immune cells within chronic inflammation, and we found that upon continuous stimulation of T cells, they can become immunosuppressive, called regulatory T cells. And these Tregs, they express cyclooxygenase, which is enzyme producing PGE2. And this enzyme is inhibited by aspirin. We could see that PGE2 could inhibit the effector T cells, so you can suppress the immune function. And we mapped that in colorectal cancer patients that found these cells present in the colorectal cancer tissue, as well as these patients had higher levels of PGE2 in the plasma.

Further on, we did some immune assays and found that these cells, these regulatory T cells, inhibited the immune function, anticancer immunity, and we could reverse that by adding NSAIDs or cyclin NP-specific inhibitor.

Taking that together, we did a register based study, which took data from Norwegian cancer registry and linked that to the prescription database of Norway from 2004 to 2011. And we analyzed around 24 000 patients and found that 1 in 4 was using aspirin and found better outcome in these patients, both all-cause mortality and cancer-specific mortality was lower in these patients. And the patients using aspirin before the diagnosis or after diagnosis had the hazard ratio point 76. So it was protective.

So how could we bring this to the clinics? That's the background for the clinical trial. And we know that the main reason of patients dying from chronic cancer is liver metastases or metastatic disease. And the best treatment for that is surgery. Although we operate them, about half of them get a recurrence in the liver. We want to know if aspirin could reduce the recurrence of colorectal cancer liver metastases.

We decided a multicenter trial, including patients from Norway, Sweden and Denmark, that's a population of around 20 million inhabitants. And we included patients operated for colorectal liver metastases without having other metastases and we excluded the patients already using aspirin or other platelet inhibitors. We randomized 466 patients to either aspirin for daily use, 160 mg for 3 years or placebo. And after following them for 3 years, which was February of this year, we analyzed the results and found that there was no difference in disease-free survival in patients using aspirin. And the same for secondary outcome for overall survival. We didn't see any difference there either. And that was a bit surprising because we have all this data of protecting against primary colorectal cancer. Especially at ASCO GI this year, the ALASKA trial was published, showing that patients with PIK3CA mutation in colorectal cancer had better overall survival or disease-free survival if they had in the aspirin group. We are now doing subgroup analyses, looking at the mutational analysis to see if there are any subgroups having benefit of aspirin with liver metastasis.

But as a whole, we can say that patients with colorectal cancer liver metastases do not benefit from having aspirin as adjuvant [treatment]. We also found they had more severe adverse events and more adverse events, so it could be actually harmful to give them aspirin, especially if it doesn't give any better outcome either. That’s the conclusion of our trial and thank you.

Source:

Yaqub S, Bjornbeth BA, Angelsen J-H, et al. Aspirin as secondary prevention for colorectal cancer liver metastases (ASAC): A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. Presented at the 2025 ASCO Annual Meeting. May 30-June 3, 2025. Abstract LBA3511.