NOTCH pathway/gamma-secretase inhibitors

One study included 17 adult patients with desmoid tumors, 15 of whom had variants in the APC or CTNNB1 genes.[32][Level of evidence C3]

One study included 17 adult patients with desmoid tumors, 15 of whom had variants in the APC or CTNNB1 genes.[32][Level of evidence C3]

Five patients (29%) achieved a confirmed partial response to nirogacestat.

One study included 17 adult patients with desmoid tumors, 15 of whom had variants in the APC or CTNNB1 genes.[32][Level of evidence C3]

Four adult patients experienced grade 1 irregular menstruation.

One study included 17 adult patients with desmoid tumors, 15 of whom had variants in the APC or CTNNB1 genes.[32][Level of evidence C3]

In a clinical trial (NCT03785964), 75% of women of childbearing potential reported events related to ovarian dysfunction.[33]

A small series included four patients younger than 20 years who received nirogacestat on a compassionate basis.[34][Level of evidence C3]

A small series included four patients younger than 20 years who received nirogacestat on a compassionate basis.[34][Level of evidence C3]

Three patients had a durable benefit, defined as a complete response (n = 1), partial response (n = 1), or stable disease (n = 1).

A small series included four patients younger than 20 years who received nirogacestat on a compassionate basis.[34][Level of evidence C3]

No patients experienced grades 3 or 4 adverse events.

The U.S. Food and Drug Administration (FDA) approved nirogacestat for the treatment of patients aged 18 years and older with progressive desmoid tumors who require systemic therapy. The approval was based on a prospective, randomized, placebo-controlled trial conducted by a consortium.[33]

The U.S. Food and Drug Administration (FDA) approved nirogacestat for the treatment of patients aged 18 years and older with progressive desmoid tumors who require systemic therapy. The approval was based on a prospective, randomized, placebo-controlled trial conducted by a consortium.[33]

In 142 patients, nirogacestat had a significant PFS benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% CI, 0.15–0.55; P < .001).

The U.S. Food and Drug Administration (FDA) approved nirogacestat for the treatment of patients aged 18 years and older with progressive desmoid tumors who require systemic therapy. The approval was based on a prospective, randomized, placebo-controlled trial conducted by a consortium.[33]

The likelihood of being event free at 2 years was 76% with nirogacestat and 44% with placebo.

The U.S. Food and Drug Administration (FDA) approved nirogacestat for the treatment of patients aged 18 years and older with progressive desmoid tumors who require systemic therapy. The approval was based on a prospective, randomized, placebo-controlled trial conducted by a consortium.[33]

Nirogacestat was associated with significant benefits related to PFS, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors.

The U.S. Food and Drug Administration (FDA) approved nirogacestat for the treatment of patients aged 18 years and older with progressive desmoid tumors who require systemic therapy. The approval was based on a prospective, randomized, placebo-controlled trial conducted by a consortium.[33]

Nirogacestat was associated with a significant risk of ovarian failure.