The FDA has approved nirogacestat (Ogsiveo) for adult patients with progressing desmoid tumors who require systemic treatment.
The phase 3 DeFi trial in which nirogacestat resulted in a 71% reduction in the risk of disease progression or death vs placebo in this population.
The median progression-free survival (PFS) in the investigative arm was not yet reached vs 15.1 months in the placebo arm.
PFS data were supported by change from baseline in patient-reported worst pain favoring the nirogacestat arm.
PFS that had been based on radiographic progression only revealed a hazard ratio of 0.31.
Nirogacestat elicited an objective response rate of 41% vs 8% with placebo.
Of those who responded to nirogacestat, 7% achieved a complete response and 34% experienced a partial response; in the placebo arm, these rates were 0% and 8%, respectively.
This is the first approved treatment for desmoid tumors.
Desmoid tumors are difficult to manage due to their invasive nature and high rates of recurrence.
A total of 142 patients were randomly assigned to receive 150 mg of oral nirogacestat or placebo twice daily.
Progressive free survival, and overall response rates were in favor of nirogacestat irrespective of baseline characteristics including sex, tumor location, tumor focality, treatment status, prior therapies received, mutational status, and history of familial adenomatous polyposis.
The median time to first response with nirogacestat was 5.6 months vs 11.1 months with placebo.
Improvements in patient-reported outcomes were also observed with nirogacestat vs placeboas it related to pain, tumor–specific symptoms physical/role functioning and overall health-related quality of life.
Twenty percent of patients experienced serious adverse effects.
Dose reductions and interruptions were needed in 41% and 51% of patients, respectively.
20% of patients permanently discontinued nirogacestat due to AEs.
AEs that led to discontinuation of therapy included diarrhea, ovarian toxicity, increased alanine aminotransferase, and increased aspartate aminotransferase.
The most common any-grade AEs experienced by at least 15% of patients in the nirogacestat and placebo arms: respectively, were diarrhea (84% vs 35%), nausea (54% vs 39%), stomatitis (39% vs 4%), abdominal pain (22% vs 14%), ovarian toxicity (75% vs 0%), rash (68% vs 14%), alopecia (19% vs 1.4%), fatigue (54% vs 38%), headache (30% vs 15%), cough (20% vs 6%), dyspnea (16% vs 6%), upper respiratory tract infection (17% vs 2.8%).
In at least 15% of patients had decreased phosphate (65% vs 11%) and potassium (22% vs 4.2%), and increased urine glucose (51% vs 0%), urine protein (40% vs 25%), AST (33% vs 18%), and ALT (30% vs 21%) vs placebo.