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 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.
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.
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.