Aspirin Fails to Boost Survival in Colorectal Cancer Trial

Treating patients with aspirin after completion of standard adjuvant therapy for colorectal cancer failed to significantly improve disease-free survival (DFS) and overall survival, the phase III randomized ASCOLT study showed.

Among 1,550 patients included in the modified intention-to-treat analysis, the 5-year DFS rate was 77% for those who received aspirin 200 mg daily for 3 years compared with 74.8% for those who received placebo (HR 0.91, 95% CI 0.73-1.13, P=0.38), reported Han Chong Toh, MBBChir, of the National Cancer Centre Singapore, and colleagues.

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), according to the findings in Lancet Gastroenterology & Hepatology.

Any-grade adverse events were reported in 49% of patients in the aspirin group versus 51% in the placebo group, while serious adverse events were reported in 12% and 14%, respectively.

“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,” Toh and colleagues wrote. “Biomarker studies and a planned prospective meta-analysis with similar ongoing aspirin trials will help to confirm or exclude efficacy. These could be impactful globally given the low cost of aspirin and its tolerability.”

“For this reason, it is important that these trials continue until completion,” they added.

In a commentary accompanying the study, Seohyuk Lee, MD, of Beth Israel Deaconess Medical Center in Boston, and Mingyang Song, MBBS, ScD, of the Harvard T.H. Chan School of Public Health and Massachusetts General Hospital in Boston, also suggested that the study’s findings and methodology “have important implications for ongoing trials and future studies.”

They noted, for example, that “the timing and duration of aspirin treatment necessary in the post-colorectal cancer diagnosis setting remain unknown,” but previous research has suggested that regular aspirin use prior to diagnosis might improve survival. However, they pointed out that this trial excluded patients who were on active aspirin treatment at enrollment, and did not assess past aspirin use.

They also observed that while aspirin was evaluated at a daily dose of 200 mg, the dose associated with an optimal risk-benefit profile is unclear.

Finally, Lee and Song noted that while roughly a third of patients with newly diagnosed colorectal cancer have been shown to also have cardiovascular disease, and that many patients with cardiovascular disease are on chronic aspirin therapy for secondary prevention, ASCOLT excluded patients with a history of clinically significant cardiovascular disease or stroke.

“Thus, patients with coexisting colorectal cancer and cardiovascular disease could reflect a specific subpopulation in which aspirin therapy might be of particular importance,” they wrote.

The ASCOLT trial was conducted at 66 sites across 11 countries and territories in Asia-Pacific and the Middle East. The modified intention-to-treat analysis included 1,550 colorectal cancer patients who had undergone resection and had completed standard adjuvant therapy (at least 3 months of chemotherapy). 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. Median follow-up at data cutoff was 59.2 months.

Among adverse events of special interest, there were no cases of acute myocardial infarction in the aspirin group versus two in the placebo group (one serious adverse event), no ischemic cerebrovascular events in the aspirin group versus two in the placebo group (one serious adverse event), and three major gastrointestinal bleeds in the aspirin group versus one in the placebo group (two serious events in the aspirin group vs one in the placebo group).

Treatment was permanently discontinued early due to an adverse event in 10% of patients in the aspirin group versus 9% in the placebo group.

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