Aspirin treatment following standard adjuvant therapy for colorectal cancer did not significantly improve disease-free survival (DFS) or overall survival, according to results from the phase III ASCOLT study. The findings, published in Lancet Gastroenterology & Hepatology, indicate that aspirin, while well-tolerated, did not provide a statistically significant reduction in colorectal cancer recurrence.
The multi-center trial, conducted across 66 sites in 11 countries and territories in Asia-Pacific and the Middle East, randomized 1,550 patients who had undergone resection and completed adjuvant chemotherapy to either 200 mg of aspirin daily or placebo for 3 years. The median follow-up was 59.2 months.
Key Findings on Survival Rates
The 5-year DFS rate was 77% in the aspirin group compared to 74.8% in the placebo group (HR 0.91, 95% CI 0.73-1.13, P=0.38). The 5-year overall survival rate was 91.4% in the aspirin group and 88.9% in the placebo group (HR 0.75, 95% CI 0.53-1.07, P=0.11). These results suggest that aspirin did not provide a significant survival advantage in this patient population.
Adverse Events and Tolerability
Adverse events were similar between the two groups, with any-grade adverse events reported in 49% of patients in the aspirin group and 51% in the placebo group. Serious adverse events occurred in 12% and 14% of patients, respectively. There were three major gastrointestinal bleeds in the aspirin group versus one in the placebo group.
Implications and Future Research
"The trial shows that aspirin is well tolerated in this patient group but does not demonstrate a significant reduction in colorectal cancer recurrence over placebo, although a more modest benefit could not be excluded," wrote Han Chong Toh, MBBChir, of the National Cancer Centre Singapore, and colleagues. They emphasized the importance of ongoing trials and planned meta-analyses to confirm or exclude efficacy, particularly given aspirin's low cost and tolerability.
In an accompanying commentary, Seohyuk Lee, MD, of Beth Israel Deaconess Medical Center, and Mingyang Song, MBBS, ScD, of Harvard T.H. Chan School of Public Health, highlighted the importance of the study's findings for future research. They noted that the optimal timing, duration, and dosage of aspirin treatment in the post-colorectal cancer setting remain unclear. The ASCOLT trial excluded patients on active aspirin treatment at enrollment and those with a history of clinically significant cardiovascular disease or stroke, potentially missing a subpopulation where aspirin might be particularly beneficial, as roughly a third of patients with newly diagnosed colorectal cancer also have cardiovascular disease.
Trial Design and Patient Population
The modified intention-to-treat analysis included 1,550 colorectal cancer patients who had undergone resection and completed standard adjuvant therapy (at least 3 months of chemotherapy). The median age was 57 years, 58% were men, 17% had Dukes' B colon cancer, 50% had Dukes' C colon cancer, and 33% had rectal cancer. Patients were randomized 1:1 to aspirin 200 mg daily or placebo from February 2009 through June 2021.
