Retrospective Case Series Highlighting the Real‐World Experience of Nirogacestat Therapy in Young Adults With Desmoid Tumors

Background With a peak incidence in young adulthood, desmoid tumors (DTs) often cause pain, loss of function, and diminished quality of life. On the basis of findings from the Phase III desmoid fibromatosis (DeFi) trial, the selective gamma secretase inhibitor nirogacestat was approved by the US Food and Drug Administration (FDA) in November 2023 for the treatment of patients with DT. Methods A retrospective, single‐institution chart review of patients with DT who initiated nirogacestat therapy over a 14‐month period was undertaken. Measured real‐world outcomes included radiographic tumor response, patient‐reported pain, and toxicities attributable to nirogacestat. Results Eleven young adult (YA) patients with DT who received nirogacestat were identified for the study. The median patient age was 26 years. The median duration of therapy at the time of the study was 8 months. RECIST responses included one patient with a partial response (PR), eight with stable disease (SD), and two were deemed radiologically inevaluable. Eight out of nine evaluable patients (88%) demonstrated a reduction in tumor volume and improvement in magnetic resonance imaging (MRI) T2‐weighted signal intensity. Nine out of 10 patients who presented with pain (90%) reported rapid improvement. The most common toxicities included diarrhea, nausea, rash, and ovarian dysfunction. Discontinuation of nirogacestat was necessary in one patient due to severe diarrhea. Out of nine female patients, two elected to undergo oocyte cryopreservation prior to starting therapy. Conclusions Nirogacestat provided therapeutic benefit in the majority of the YA DT population with rapid and sustained pain relief. The toxicity profile was generally predictable and manageable. The experience expands upon the findings of the DeFi Trial, defining the real‐world benefits, toxicities, and supportive care needs.