In patients with the genetic syndrome FAP, surgery for mesenteric desmoids is strongly contraindicated. The wound healing process itself is believed to initiate tumor growth, making surgery a potential cause, not a cure, unless for an anatomical emergency.
The Phase III DEFI trial for nirogacestat uncovered ovarian toxicity, a previously unexpected side effect. This discovery was a direct result of enrolling a patient population that accurately reflected the disease's high prevalence in young women of childbearing potential.
The approval of effective therapies like nirogacestat creates an ethical dilemma. For patients with progressing tumors, continuing to use a placebo arm in clinical trials may no longer be appropriate, challenging future research design for this rare disease.
Desmoid tumors can shrink without treatment, a phenomenon seen in up to 35% of patients under observation. This inherent biological behavior makes it difficult to prove that continued tumor reduction during long-term therapy is solely due to the drug's effect.