What treatments are being tested for Lynch syndrome? What are the clinical trials?

The short version: the clinical trials for Lynch syndrome focus on aspirin chemoprevention and colonoscopy quality, not on new drug treatments.

The CAPP2 trial is the only randomized controlled trial in this retrieval that tests a drug intervention for Lynch syndrome. It gave 600 mg of aspirin daily or a placebo to carriers and followed them for a mean of about 55 months. The main analysis showed a hazard ratio of 0.63 for colorectal cancer, but the p-value was 0.12, meaning the result could be due to chance [2]. The per-protocol analysis (people who actually took the aspirin) showed a stronger effect: a hazard ratio of 0.41 with a p-value of 0.02 [2]. That is a real signal, but the trial was not designed to prove aspirin works. It was designed to test the idea, and the long-term follow-up later confirmed a benefit. The CAPP2 trial was funded by cancer research charities, not by a drug company.

The other trials in this retrieval are not testing drugs. One study proposes a "Leiden Quality Score" to rate colonoscopy quality in Lynch syndrome patients, from "very good" (99% certain no polyps missed) down to "inadequate" (only large polyps excluded) [3]. That is a quality-improvement tool, not a treatment. The 2014 consensus guideline lists daily aspirin as a potential benefit but does not cite a trial that tested it in Lynch syndrome beyond CAPP2 [1]. The same guideline recommends colectomy and prophylactic hysterectomy or oophorectomy, but those are surgeries, not clinical trials [1].

What is missing from this retrieval is any trial testing a new drug, a vaccine, or an immunotherapy for Lynch syndrome. No PD-1 inhibitor trials, no checkpoint inhibitor trials, no DNA repair inhibitor trials appear in these records. The active clinical trial landscape for Lynch syndrome is broader than what this search found, but on the evidence here, the only drug with trial data is aspirin, and the only intervention with a quality trial is colonoscopy.

My call: aspirin has the best trial evidence for reducing colorectal cancer risk in Lynch syndrome, but the evidence is moderate, not definitive. Confidence: moderate.