NIROGACESTAT TAB
Clinical Criteria Summary
Document 711
Exclusion Criteria
- Severe renal impairment (e.g., eGFR < 40 ml/min/1.73m2)
- Severe hepatic impairment (e.g., Child-Pugh Class C)
- Unmanageable drug-drug interactions (e.g., concomitant CYP3A inhibitors/inducers, proton pump inhibitors, etc.)
- Active or uncontrolled infection
- Known pregnancy
- Lactation
Inclusion Criteria
- Diagnosis of progressive desmoid tumor
- Progressive disease or unmanageable toxicity from prior treatment with a tyrosine kinase inhibitor (e.g., sorafenib or pazopanib), unless contraindicated
- Care is provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Additional Inclusion Criteria
- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits, the use of effective contraception and avoid breastfeeding during therapy and for 1 week after stopping treatment.
Document 712
Indication & Patient Population
- Adult patients with progressing desmoid tumors who require systemic treatment
- Patients with desmoid tumors not amenable to surgery
- Patients who have not received previous treatment or have refractory/recurrent disease after >1 line of therapy (defined as >20% progression according to RECIST within 12 months before screening)
Dosing & Administration
- 150 mg orally twice daily
- Administered in continuous 28-day cycles
- Continue until disease progression or unacceptable toxicity
Monitoring & Safety Considerations
- Monitor for diarrhea, ovarian toxicity, hepatotoxicity, electrolyte abnormalities, and embryo-fetal toxicity
- Ovarian toxicity: Female reproductive function and fertility may be impaired; reversible upon discontinuation
- Hepatotoxicity: AST increased in 30% of patients; ALT increased in 33%
- Assess patient-reported outcomes including pain intensity, physical function, role function, and quality of life
Contraindications & Warnings
- No boxed warnings or contraindications stated
- Avoid strong or moderate CYP3A4 inducers and inhibitors
- Avoid PPIs and H2 antagonists
Guideline & Pathway Criteria
- FDA-approved therapy for progressive desmoid tumors
- NCCN: Preferred category 1 along with sorafenib
- VA STS pathway: Systemic therapy indicated for desmoid tumors with anatomic location showing morbid progression
- Selection between nirogacestat and alternative TKIs (e.g., sorafenib) should be directed by patient symptoms, comorbidities, and toxicity profile
Clinical Context & Use Considerations
- Desmoid tumors are rare, slow-growing, locally invasive mesenchymal tumors with no potential to metastasize; 20-30% may spontaneously regress
- Management depends on tumor location, symptoms, and progression; may involve surveillance, surgery, radiation, local ablation, cytotoxic chemotherapy, or TKI therapy
- If rapid response is needed or oral absorption is compromised, cytotoxic chemotherapy may be preferred
- Nirogacestat evidence demonstrates benefit in pain reduction, physical functioning, and quality of life compared to placebo