Effect of chemoprevention by low-dose aspirin of new or recurrent colorectal adenomas in patients with Lynch syndrome (AAS-Lynch): study protocol for a multicenter, double-blind, placebo-controlled randomized controlled trial

Abstract

Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC) and confers a high lifetime risk of CRC estimated to be up to 60%. Colonoscopy is recommended every 2 years in LS patients above the 20-25year-old age bracket, and every year when colonic neoplasia has been detected. Efficient chemoprevention has the potential to represent a cost-effective intervention in these high-risk patients and could allow a delay in colonoscopy surveillance. Several epidemiological studies have shown that regular use of low dose aspirin is associated with a 20 to 30% reduction in the risk of sporadic colonic adenomas and colorectal cancer regardless of family risk. However, in recent large randomized trials in specific populations, aspirin use showed no protection for colorectal cancer. A prospective randomized CAPP-2 trial evaluated the effect of aspirin use in LS patients. The primary analysis of this trial showed no significant decrease in CRC in LS patients under daily aspirin. However, a preplanned secondary analysis after an extended follow-up showed a significant reduced risk of CRC in the aspirin group in the per-protocol analysis. The real effect and clinical benefit of aspirin are still to be consolidated in this population. The AAS-Lynch trial-a prospective, multicentric, double-blind, placebo-controlled, randomized clinical trial-was designed to investigate if daily aspirin therapy, at a dose of 100 or 300 mg, would decrease the occurrence or recurrence of colorectal adenomas in patients under 75 years of age, compared with placebo. Trial registration: ClinicalTrials.gov NCT02813824. Registered on 27 June 2016. The trial was prospectively registered.

Pharmacogenetic Review: Germline Genetic Variants Possessing Increased Cancer Risk With Clinically Actionable Therapeutic Relationships

“…Additionally, a co-occurring tissue-specific mouse model showed naproxen modulated tumor growth and prolonged survival ( Reyes-Uribe et al, 2021 ). Currently underway are two additional randomized clinical trials, CAPP3 and AAS-Lynch, which share a primary endpoint of comparing the effectiveness of varying aspirin doses in preventing colorectal cancer in Lynch Syndrome patients ( Soualy et al, 2020 ).…”

Chemoprevention in hereditary digestive neoplasia: A comprehensive review

“…The French AAS-Lynch study is a randomized trial conducted in 34 centers that enrolled 424 patients with Lynch syndrome and evaluated the effect of supplementation with aspirin 100 or 300 mg daily versus placebo. 100 The primary endpoint is the number of patients who developed at least one colonic adenoma, detected by chromoendoscopy, during the 4-year follow-up, after complete removal of all polyps at the inclusion colonoscopy. This trial includes a nutritional and physical activity questionnaire as well as a ‘shotgun’ metagenomic microbiota study.…”

Lynch Syndrome: From Carcinogenesis to Prevention Interventions

“…To try to answer this, the CAPP-3 trial is currently ongoing, which aims to compare the effects of different doses of aspirin (100 mg, 300 mg, and 600 mg) in patients with LS. Analogously, at least two other ongoing trials have compared the efficacy of different doses of aspirin in CRC chemoprevention: the AAS-Lynch trial aims to evaluate the effect of 300 mg versus 100 mg versus the placebo for 4 years in LS patients [ 105 ]; and the ADD-aspirin protocol including four randomized phase 3 trial evaluating different doses of aspirin in patients over and under 75 years as an adjuvant therapy for different cancer, among these CRC, even if not specifically for LS patients [ 106 ].…”