As reported in the Journal of Clinical Oncology by Ratan et al, long-term follow-up in the phase III DeFi trial has shown maintained benefits with prolonged nirogacestat treatment in patients with desmoid tumors.
Study Details
In the double-blind trial, 142 patients with progressing desmoid tumors were randomly assigned to receive nirogacestat at 150 mg (n = 70) or placebo (n = 72) twice daily in continuous 28-day cycles. At the primary analysis (data cutoff in April 2022), the nirogacestat group had significant improvement vs placebo in progression-free survival, objective response rate, and patient-reported outcomes (PROs) with a median exposure to nirogacestat of 20.6 months (range = 0.3–33.6 months).
Key Findings
In the current analysis in the nirogacestat group (data cutoff in December 2024), median exposure was 33.6 months (range = 0.3–61.8 months).
Median progression-free survival was not reached. Objective response was observed in 32 (45.7%) of 70 patients, with improvements from 34.3% at 1 year to 41.4% at 2 years and 44.3% at 3 years. Responses since the primary analysis consisted of three additional partial responses and three additional complete responses. Additional reductions in target tumor size were observed in most patients.
Benefits in PROs were sustained during continued treatment. Adverse events frequently reported during earlier treatment decreased in incidence and severity over time. After the primary analysis, nirogacestat was discontinued in four patients due to adverse events between years 2 and 4.
The investigators concluded: “[L]ong-term continuous nirogacestat treatment was associated with further tumor size reductions, durable objective responses, sustained PRO benefits, and a manageable safety profile consistent with the primary analysis.”
Ravin Ratan, MD, of The University of Texas MD Anderson Cancer Center, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, Houston, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by SpringWorks Therapeutics, Inc. For full disclosures of all study authors, visit ascopubs.org.
