(P 36) EARLY REAL-WORLD EXPERIENCE WITH THE USE OF NIROGACESTAT FOR THE TREATMENT OF DESMOID FIBROMATOSIS

Objective: Desmoid tumors are rare, often locally aggressive, and highly recurrent soft-tissue tumors. Though previously treated primarily with surgical resection, current management strategies often recommend systemic therapy as first line treatment. Nirogacestat, an oral gamma secretase inhibitor, was approved in November 2023 for the management of desmoid tumors. Here, we report our initial experience with the use of Nirogacestat for the management of desmoid tumors since its FDA approval.

Methods: Following IRB approval, we conducted a single-institution retrospective review of all patients with desmoid tumors treated between July 2015 and May 2024. All patients with at least two clinical visits were included, those who sought a second opinion at our institution but were treated locally were excluded. Patients were asked to complete the Brief Pain Inventory (BPI) at all visits subsequent to November 2023. BPI scores and subjective reports of change in desmoid tumor size were reported. Change in tumor size was measured over subsequent imaging studies. Follow up was through May 15, 2024.

Results: In total, we identified 51 patients with desmoid tumors treated at our institution since July 2015. Of these, 16 patients were offered treatment with Nirogacestat since November 2023, and 13 initiated treatment with Nirogacestat. Patients were heavily pretreated, with eight (n=8/16, 50%) having received previous surgical resection, four (n=4/16, 25%) having received radiation, and six (n=6/16, 38%) having received previous systemic therapy, with a median of three previous lines of systemic therapy. Tumors were located in the lower extremity (n=5/16, 31%), chest/abdominal wall (n=4/16, 25%), upper extremity (n=3/16, 19%), intraabdominal (n=3/16, 19%), and the soft tissues of the trunk (n=1/16, 6%). The dominant presenting symptom was local pain (n=14/16, 87%) and, for tumors in the extremity, decreased range of motion (n=4/8, 50%). Two of the three patients who declined Nirogacestat did so because of concerns regarding ovarian suppression, the other was satisfied with her current systemic therapy regimen. Of the 13 patients that initiated Nirogacestat, one discontinued due to an allergic reaction, two reported manageable diarrhea, and one patient reported symptoms of withdrawal due to missed doses. Of the six patients who completed the BPI at presentation, three (50%) reported pain at presentation, one of whom reported decreased pain at follow up. Several patients reported improvement in subjective symptoms, often within several weeks of initiating Nirogacestat. On early surveillance imaging on Nirogacestat, two patients have undergone repeat imaging, both of whom have had tumors decrease in size according to RECIST criteria.

Conclusion: Early real-world experience with the use of Nirogacestat confirms that it is well tolerated and that most side-effects are manageable without requiring discontinuation. So far, we have seen early subjective pain relief, improved range of motion, and even decrease in tumor size on imaging done within a few months of starting Nirogacestat, matching clinical improvement. Follow up is limited, but we anticipate median follow up of approximately 9 months in November 2024.