57MO Impact of nirogacestat (niro) on patient-reported outcomes (PROs) in adults with desmoid tumor with a best overall response (BOR) of stable disease (SD): Post hoc analysis from the DeFi study

Desmoid tumors (DT) are rare, soft-tissue tumors associated with a potentially debilitating burden. Niro—a targeted gamma secretase inhibitor—is the first systemic treatment for DT approved in the US. In the phase 3 DeFi study, niro demonstrated statistically significant and clinically meaningful improvement vs placebo (pbo) in progression-free survival (PFS), objective response rate (ORR), and PROs of pain, DT-specific symptom burden, physical and role functioning, and overall quality of life (QoL). As DT can have an unpredictable disease course, an improvement in PROs during SD is important to assess, especially during systemic therapy. DeFi was a global, multicenter, double-blind study to determine the efficacy, safety, and tolerability of niro in adults with progressing DT. Patients were randomized to receive niro (150 mg) or pbo twice-daily taken in continuous 28-day cycles. Primary endpoint was PFS; key secondary endpoints were ORR by RECIST 1.1 and change from baseline in PROs (BPI-SF, GODDESS, and EORTC QLQ-C30) at treatment Cycle 10. Post hoc analyses of PROs were conducted in patients with a BOR of SD (07Apr2022 datacut). ORR was significantly greater with niro (29/70 [41%]) than pbo (6/72 [8%]; P<0.001). A total of 35/70 (50%) niro-group patients had a BOR of SD vs 55/72 (76%) pbo-group patients. Niro-treated patients with a BOR of SD had significantly greater improvement from baseline in all PROs at Cycle 10 than pbo (Table). Table: 57MOBOR of SD: Change from BL at Cycle 10, least-squares meanNiro (n=35)Pbo (n=55)P-valueBPI-SF: Brief Pain Inventory-Short FormaWorst pain−1.480.13c<.001GODDESS: Gounder/Desmoid Tumor Research Foundation Desmoid Symptom/Impact ScaleaTotal symptom score (DT Symptom Scale [DTSS])−1.130.68c<.001Physical functioning domain (DT Impact Scale [DTIS])−0.530.16c<.001EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30bPhysical functioning7.93−5.32c<.001Role functioning5.05−13.29c=.006Overall QoL4.05−9.02d=.014aNegative = improve; bPositive = improve; cBL n=54; dBL n=53. BL, baseline. Open table in a new tab aNegative = improve; bPositive = improve; cBL n=54; dBL n=53. BL, baseline. In this post hoc analysis of the DeFi study, patients that achieved RECIST SD as BOR had significantly greater improvement with niro than pbo in pain and DT-specific symptom burden, physical and role functioning, and overall QoL. These results suggest that niro can provide clinically meaningful benefits for patients with DT, including those with RECIST SD as best response.