Intermittent or stop-and-restart nirogacestat in desmoid tumours

Desmoid tumours are not cancers, do not metastasise and often stop growing on their own, yet nirogacestat, tested in the DeFi trial, is given continuously and causes ovarian failure. This idea proposes treating to best response, then pausing the drug and restarting only on progression. DeFi showed durable responses and ovarian toxicity that reverses when the drug is stopped, and a debate in JCO in 2026 has questioned long-term continuous use; the rationale is that toxicity depends on dose and duration and is reversible. The proposed test is a randomised discontinuation trial after twelve months of response with time to progression and ovarian function as co-primary endpoints; the idea is speculative and addresses the bottleneck of wrong doses, alongside the adaptive-therapy platform idea.