The Ascolt trial explores the role of aspirin in preventing colorectal cancer recurrence

A large, international, multicenter, phase 3 clinical trial of aspirin for the secondary prevention of colorectal cancer has concluded. The Ascolt (aspirin after completion of standard adjuvant therapy for colorectal cancer) trial, led by a clinical physician scientist in Singapore, is the first phase 3 trial to evaluate the efficacy and safety of aspirin in preventing recurrence of colorectal cancer following care surgery and adjuvant chemotherapy treatment. This study was published in Lancet Gastroenterology and Hepatology It was featured online in January 2025 on the cover of the March 2025 printed issue of the journal.

Ascolt results report that aspirin does not statistically improve disease-free survival in all patients. Still, they clearly demonstrate a consistent trend in aspirin to improve disease-free and overall survival over the years. In January 2025, the same month that Ascort's results were published, positive results from a phase 3 study of colorectal cancer patients in Northern Europe. pik3ca Mutations – using aspirin for secondary prevention and adjuvant chemotherapy after surgery – have been announced and demonstrated that aspirin taken for up to three years is effective in people with mutations. ALASCCA trials showed that aspirin use in this particular colorectal cancer population could reduce recurrence by more than 50%. This is a huge advantage. Together, these two landmark studies tell the potential role of aspirin in reducing recurrence of colorectal cancer in specific subgroups.

Why aspirin for cancer recurrence?

Over the past 20 years, there has been no therapeutic advances in treating colorectal cancer that has been resected to reduce the risk of recurrence. All trials led by major pharmaceutical companies that added biological antibodies to standard chemotherapy have failed to further improve survival outcomes for these patients.

In 2008, Senior Clinicians at the National Cancer Centre of Singapore (NCCS) Professor Toh Hancheong and Dr. John Cheer conceptualized and tested Ascolt as a randomized controlled trial. Effectiveness Safety to prevent recurrence of colorectal cancer in patients who have completed standard care surgery and adjuvant chemotherapy using aspirin. The Ascolt exam was driven by three main motivations: (1) aspirin is inexpensive and widely accessible, (2) the urgent need to test reused drugs such as aspirin for chemoprevention as the cost of cancer drugs, and (3) studies have shown the possibility of aspirin developing colon polyps and risk of colon cancer.

Aspirin functions by inhibiting the activity of cyclooxygenase (COX) 1 and 2 enzymes. inflammation. Previous observational studies have shown that aspirin reduces intestinal polyps in healthy people with previous polyps and polyps in colorectal cancer survivors. Aspirin has been proven to reduce the incidence of colon cancer in patients with Lynch syndrome in large, randomized phase 3 trials. However, there was little data on the possibility of aspirin reducing the risk of cancer in patients who had already been diagnosed with colon cancer.

Ascolt: Clinician-promoted global trials

The ASCOLT trial recruited an international multicenter, randomized, double-blind, placebo-controlled phase 3 trial, randomly assigned 1,587 patients with colorectal cancer who completed standard care to one of two groups. Of these patients, 1,550 participants were included in the analysis population.

The Ascort ran between 2009 and 2021 and was conducted in 66 hospitals across 11 countries and territories, including Australia, China, India, Indonesia, Malaysia, New Zealand, Saudi Arabia, Singapore, Sri Lanka, South Korea and Taiwan. Two large consortiums: the Indox Research Network, the Institute of Cancer Medicine at Oxford University, and India's top nine comprehensive cancer centres, including AIMS (All India Medical Institute) and TATA Memorial Hospital in Mumbai, and the Australian Gastrogen Trial Group (AGITG) were key members of the Ascolt trials.

The ambitious, large-scale global research has faced many challenges, including coordinating test logistics across multiple countries and territories, navigating Covid-19 pandemic restrictions, and raising adequate funds. As Ascolt was an investigator-initiated exam, the additional financial support protected by Professor Toh and Dr. Chia was an important lifeline to support operations, completion and follow-up for over 15 years.

Negative consequences of silver lining

The results of the Ascort trial did not meet its primary endpoint as we did not find statistically significant survival rates of colorectal cancer patients who completed standard therapy when compared to placebo. Still, Ascolt has shown a clear and consistent trend over the years, although small, albeit in the disease-free and overall survival benefits of aspirin and placebo aspirin. Importantly, Ascolt showed that aspirin was tolerated for up to 3 years with no significant side effects. In fact, the side-effect profile of aspirin was comparable to the side-effect profile of the placebo group.

Previous data suggested specific molecular features including pik3ca Mutations and COX2 expression in colorectal cancer tissues can identify individuals who may most likely benefit from taking aspirin to reduce recurrence of colorectal cancer. Results of the ALASCCA trial, recruiting patients in Sweden, Denmark, Finland and Norway in January 2025, indicated the use of aspirin in patients. pik3ca-Mutated colorectal cancer reduced the risk of recurrence by more than 50% compared to placebo. This is the first prospective trial to demonstrate that aspirin can effectively target selected items Biomarkers– A subset identified to reduce recurrence of colorectal cancer.

Ascolt and Alascca provide important insights into the use of aspirin as an adjunctive therapy for colorectal cancer and catalyze the next step for further research and validation. Field leaders expect that aspirin will become part of the treatment system for early stage colorectal cancer in the near future, with a biomarker-identified subset. This is an impactful global health benefit that will make a positive difference to one of the most common cancers in the world.

Next steps for Ascolt clinical researchers and researchers

“Ascolt lays the foundation and identifies the role of aspirin in a more selected biomarker identification population, reducing the risk of colorectal cancer recurrence after standard surgery and chemotherapy.” Lancet Gastroenterology and Hepatology Senior Author Professor of Study, Professor Toh, Senior Consultant in the Faculty of Medical Oncology, and Associate Chief Executive Officer of NCCS (Strategic Partnership). “We are already beginning to analyze promising molecular targets. pik3ca Mutations and COX2 expression in Ascort patient cohorts in close collaboration with colleagues from the Australian and New Zealand's Ascort Consortium. While Alascca's results are exciting due to the prominent benefits of aspirin in the Scandinavian population, it remains important to see whether these findings can be examined in more diverse ethnic groups. ”

It is essential that the global academic consortium continues to lead large trials asking key questions such as whether affordable off-patient medications can benefit cancer patients and patients of many disease types. If proven useful, such drugs offer powerful global health benefits, especially for patients in low- and middle-income countries (LMIC). ”

Professor Toh Han Chong, Senior Consultant for the Faculty of Medical Oncology, Senior Consultant for the Faculty of Medical Oncology and Associate Chief Executive Officer (Strategic Partnership)

“With all the combined efforts, we intend to define the role of aspirin in the treatment of established cancer,” said Dr. Chia, the first author of the study. “This is very important as aspirin is very affordable and could prove to be the most cost-effective cancer treatment of the future.