(P 35) EARLY REAL WORLD EXPERIENCE WITH NIROGACESTAT IN PATIENTS WITH DESMOID FIBROMATOSIS

Objective: Desmoid fibromatosis is extremely rare disease with prevalence of 3-5 cases per million annually. Multiple treatment modalities have been used but with limited success. Nirogacestat with g-secretase inhibitor activity was recently approved for the use for patients with Desmoid fibromatosis with good response in both clinical and radiological outcomes based on the results of the DeFi trial. Here, we are reporting a series of 8 cases treated with nirogacestat at a SARC center.

Methods: Patients treated with nirogacestat were identified from our IRB approved Soft Tissue Sarcoma Tumor Registry at Roswell Park Comprehensive Cancer Center. Data related to patient’s demographic, investigations, treatment, and outcomes were retrospectively collected by EHR review. Follow up scans were done at 3-month intervals. All data were reported with descriptive analyses.

Results: 8 patients (4 female, median age of diagnosis 45.5 years, 4/8 Intraabdominal, 3/8 prior history of tumor resection) were treated with nirogacestat since approval with ramp-up dosing. 7/8 patients received at least 1 line of treatment before, and 1 patient transitioned to hospice care because of the diagnosis of an unrelated second primary malignancy and was not included in the final analysis. Majority of patients transitioned from sorafenib treatment. 4/7 patients had clinical response with relief in either pain or QOL. 3-month follow-up scans were obtained in 6 patients. 4/6 patients had radiological response with decrease in size of the primary tumor at 3 months. 6-months follow up scan was obtained in 2 patients and 1 patient had progression of disease. However, due to frequent dose disruptions for AEs, it is not known if the patient received sufficient dose of drug and continues on treatment. In terms of side effects, 5/7 had fatigue, 4/7 diarrhea, 2/7 nausea, 4/7 skin rash, 3/7 headache, and 3/7 chronic hypophosphatemia. In terms of unique adverse effects, 5/7 patients reported upper respiratory tract symptoms, and 1/7 patient had visual floaters requiring dose reduction to 50mg BID with response. 1/7 patient tolerated 150 mg BID dose, 2/7 patients tolerated 100mg BID dose, and 3/7 patients were treated with 100mg AM and 150mg PM dose. Reason for dose reduction includes skin rash in 2/6 patients, 1/6 chronic URI symptoms, 1/6 floaters, 1/6 fatigue, and 1/6 headache. Grading will be reported. In terms of unique adverse effects. Timing of best response to prior regimens, including sorafenib, will be reported, and compared to timing of best response to nirogacestat. Average number of dose holds and length of dose interruption will also be reported.

Conclusion: Nirogacestat was tolerated in desmoid tumors but required frequent dose reduction and holds; despite dose reductions, early responses were seen in majority of patients at their maximum tolerated dose. Longer outcome data is pending, as well as studies of ovarian reserve in the female patients.