Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial

Long-term follow-up from the CAPP2 trial (mean 10 years), in which 861 patients with Lynch syndrome were randomised to 600mg aspirin daily or placebo, found colorectal cancer developed in 9% v 13%, respectively (HR 0.65; 95% CI 0.43–0.97; p=0.035).

SPS commentary:

A statistically significant reduction in colorectal cancer was also reported in the per protocol analysis, including those patients who completed 2 years of the intervention (HR 0.56; 95% CI 0.34-0.91; p=0.019).

A related commentary notes there was no statistically significant benefit observed in the intention-to-treat population in earlier analyses, and that the benefit emerged 5 years after randomisation. In addition, a legacy effect was identified, whereby patients taking aspirin for a finite duration (mean 25 months) had a sustained reduction in colorectal cancer incidence persisting for 20 years. The authors say that these findings, suggesting only 24 people with Lynch syndrome need to be treated with 600mg/day aspirin to prevent one case of colorectal cancer, should strengthen existing guidelines that aspirin be considered for these individuals. Nonetheless, questions about optimal dose, duration and patient selection remain. Although major bleeding and other adverse events were no more frequent in the aspirin group than placebo, the participants were relatively young (mean 45 years at randomisation). Data from the CaPP3 trial, which is evaluating lower doses of aspirin in patients with Lynch syndrome, are eagerly awaited. Until then, the commentary suggests that the updated CAPP2 findings provide a “compelling rationale for broader aspirin use in most Lynch syndrome carriers with dosing and duration tailored according to individual risks and benefits.”


The Lancet

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