Real-World Study Demonstrates Rapid Pain Relief, Durable Disease Control, and Manageable Safety With Nirogacestat in Young Adults With Desmoid Tumors

Clinical Summary:

• Design/Population: This retrospective, single-institution study evaluated real-world outcomes among 11 young adult patients with desmoid tumors who initiated treatment with nirogacestat over a 14-month period.
• Key Outcomes: Most evaluable patients experienced tumor shrinkage or radiographic improvement, and 90% of patients with baseline pain reported rapid symptom relief. Nirogacestat demonstrated a predictable safety profile, with gastrointestinal adverse events and ovarian dysfunction representing the most common toxicities.
• Clinical Relevance: These findings support the real-world effectiveness and tolerability of nirogacestat in young adult patients with desmoid tumors while highlighting the importance of proactive supportive care and fertility counseling.

Results from a real-world study demonstrated that nirogacestat provided meaningful clinical benefit in young adult patients with desmoid tumors, with rapid pain relief, durable disease control, and a  manageable safety profile. 

“With a peak incidence in young adulthood, desmoid tumors often cause pain, loss of function, and diminished quality of life,” stated Tyler Rutherford, DO, University of Cincinnati, Cincinnati, Ohio, and coauthors. “On the basis of findings from the Phase 3 DeFi trial, the selective gamma secretase inhibitor nirogacestat was approved by the US FDA in November 2023 for the treatment of patients with [desmoid tumors].”

In this retrospective, single-institution chart review study, investigators identified 11 young adult patients with desmoid tumors who initiated nirogacestat over a 14-month period. Real-world outcomes included radiographic tumor response, patient-reported pain, and treatment-related toxicities. 

At analysis, the median duration of treatment 8 months. By RECIST criteria, 1 patient achieved a partial response, 8 had stable disease, and 2 were radiologically nonevaluable. Among the 9 radiographically evaluable patients, 88% demonstrated tumor volume reduction accompanied by improvements in magnetic resonance imaging and T2-weighted intensity. 

Clinical benefit was also reflected in symptom improvement. Nine of 10 patients (90%) who reported pain before treatment experienced rapid pain relief following initiation of nirogacestat.

The most frequently reported adverse events included diarrhea, nausea, rash, and ovarian dysfunction. One patient discontinued treatment because of severe diarrhea. Among the 9 female patients included in the study, 2 elected to undergo oocyte cryopreservation before starting therapy. 

“Nirogacestat provided therapeutic benefit in the majority of the [young adult desmoid tumor] population with rapid and sustained pain relief,” concluded Dr Rutherford et al. “The experience expands upon the findings of the DeFi Trial, defining the real-world benefits, toxicities, and supportive care needs.”

Source:

Rutherford TA, Gilene S, Haacker L, et al. Retrospective case series highlighting the real‐world experience of nirogacestat therapy in young adults with desmoid tumors. Pediatr Blood Cancer. Published online: July 25, 2026. doi:10.1002/1545-5017.70517