Nirogacestat Linked With Improved Functional Status in Patients With Desmoid Tumors

Nirogacestat (Ogsiveo) was associated with significant and clinically meaningful improvements in functional status among patients with progressing desmoid tumors who received the drug in the phase 3 Desmoid Fibromatosis (DeFi) trial, according to results presented at the National Community Oncology Dispensing Association (NCODA) International Spring Forum in Dallas, Texas, held April 3-5, 2024.¹

The oral gamma secretase inhibitor was approved by the FDA last November to treat desmoid tumors, which are slow-growing growths in connective tissue.² The tumors can cause pain and disfigurement, with detrimental impacts on quality of life. Although the tumors are noncancerous, they can become life-threatening if they grow into nearby organs.

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DeFi (NCT03785964) evaluated the efficacy and safety of nirogacestat in adult patients with progressing desmoid tumors, and it included assessments of functional impairment, which can take the form of physical limitations (eg, difficulty walking, moving/reaching, or lifting heavy objects) or role-related impairment (eg, trouble caring for one’s children, loss of employment, relationship problems).¹ The international, double-blind, placebo-controlled trial randomly assigned patients to receive either nirogacestat (150 mg) or placebo twice daily in 28-day cycles.

Participants were asked to complete 3 questionnaires at each cycle, yielding 4 measurements of functional status: the GOunder/Desmoid Tumor Research Foundation Desmoid Impact Scale (GODDESS DTIS) Physical Functioning (PF) domain; the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), both the PF and Role Functioning (RF) domains; and the Patient-Reported Outcomes Measurement Information System Physical Function Short Form 10a (PROMIS PF10a) tool.

Across 37 sites in North America and Europe, 142 patients were randomly assigned to receive nirogacestat or placebo from May 2019 through August 2020. Investigators observed clinically meaningful and statistically meaningful improvements from baseline in GODDESS DTIS PF and EORTC QLQ-C30 PF and RF scores in the nirogacestat group compared with placebo at cycle 10, with some improvements emerging as early as cycle 2. Improvements were sustained through cycle 24.

For instance, by cycle 10, the nirogacestat group’s mean GODDESS DTIS PF score had decreased by 0.634 from baseline, indicating improvement, whereas the placebo group’s mean score increased by 0.091, indicating worsening (difference, –0.725; P < .001). Also at cycle 10, EORTC QLQ-C30 scores had improved for the nirogacestat group by 9.476 and 11.135 for the PF and RF domains, respectively, whereas the placebo group’s scores worsened by 5.377 and 5.545 (both P < .001).

At cycle 10, significantly more patients receiving nirogacestat than placebo experienced improvement from baseline in their GODDESS DTIS PF (OR, 4.85; P = .002) and EORTC QLQ-C30 PF (OR, 5.12; P = .001) scores. Nirogacestat recipients were also more likely to see an improvement in EORTC QLQ-C30 RF scores; this difference was not statistically significant but the investigators deemed it clinically meaningful (OR, 2.09; P = .067).

Analysis of PROMIS PF10a scores revealed that the mean score among the nirogacestat arm reached a level seen among the general US population at cycle 4, whereas that of the placebo arm remained below that benchmark throughout the trial.

“Improvements in functioning were consistent with improvements in pain measures, disease-related symptoms, and overall health-related quality of life previously observed with nirogacestat,” the investigators noted in the poster presented at the NCODA meeting.

These improvements on functional status scores, which encompass everyday activities including eating, dressing, walking, working, and partaking in hobbies as well as perceived dexterity and activity levels, also indicate that nirogacestat can positively impact outcomes that are important to patients.

References

1. Kasper B, Gounder MM, Ratan R, et al. Impact of nirogacestat on functional status in patients with desmoid tumors: results from the phase 3 DeFi study. Poster presented at: National Community Oncology Dispensing Association; April 3-5, 2024; Dallas, TX. Accessed April 9, 2024. https://www.ncoda.org/wp-content/uploads/2024/03/NCODA-2024-DeFi-Functioning-Encore-Poster-FINAL-26Mar2024.pdf

2. Caffrey M, Steinzor P. FDA approves nirogacestat for treatment of desmoid tumors. AJMC. November 27, 2023. Accessed April 9, 2024. https://www.ajmc.com/view/fda-approves-nirogacestat-for-treatment-of-desmoid-tumors