(P 131) PATIENT-REPORTED CONTINUED BENEFITS IN PATIENTS TREATED WITH PEXIDARTINIB FOR TENOSYNOVIAL GIANT CELL TUMOR BASED ON A REAL-WORLD STUDY IN THE UNITED STATES

Objective: Tenosynovial giant cell tumors (TGCT) are a family of neoplastic, inflammatory lesions that arise within the synovium and can be locally aggressive. Patients with TGCT frequently experience pain and joint swelling, as well as stiffness, reduced range of motion, and instability in affected joints. Disease progression can lead to additional complications, most commonly mobility impairment and joint deterioration. Pexidartinib (TURALIO), a CSF-1R antagonist, is the first and only systemic therapy approved by the FDA for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. The objective of this study was to assess symptom change over time among patients who were treated with pexidartinib for TGCT in a real-world setting.

Methods: This was a longitudinal observational study of patients receiving pexidartinib for TGCT treatment in the real-world setting. The study collected Patient Reported Outcomes (PRO) from patient surveys prospectively, and clinical data from medical charts retrospectively. The surveys were administered to adult patients enrolled in the post-market Risk Evaluation and Mitigation Strategy (REMS) program: the first wave was sent in 2021 (“Baseline”), and the final was sent in 2022 (“Follow Up”). Patients were required to be receiving pexidartinib before the baseline survey and to be on pexidartinib when they accessed the follow up survey. The surveys consisted of validated instruments that measured the following domains: (1) physical function of the upper/lower extremity by Patient-Reported Outcomes Measurement Information System physical function (PROMIS-PF); (2) joint stiffness by the one-item Worst Stiffness Numeric Rating Scale (NRS); (3) joint pain by the one-item Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale Score (NRS); (4) treatment satisfaction by the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM); and (5) change in physical function and overall symptom since initiating pexidartinib by the Patient Global Impression of Change (PGIC). The EQ-5D-5L, which measures five dimensions of health state, was additionally administered in the follow-up survey to understand patients’ general health state. The scores and paired changes from baseline were summarized by descriptive statistics and a random slope regression model was developed to adjust for the time since first pexidartinib dose.

Results: At baseline (2021), 83 participants completed the first survey. A second survey was sent to the subset of 45 patients who remained on pexidartinib treatment in 2022; 31 patients completed the follow up survey. The mean (SD) time between baseline and follow up was 1.02 (0.17) years, mean (SD) age at the follow up was 41.9 (13.70) years, and 67.7% were female. The most common tumor sites were in the knee (67.7%) or ankle (16.1%). Majority of patients (59.0%) at baseline reported ‘much improved’ or ‘very much improved’ physical function with pexidartinib treatment compared to life before pexidartinib treatment (Table 1). Further, there was a non-significant change in PROMIS-PF score from baseline to follow up with mean (SD) of -0.43 (5.724) (Table 2), indicating stability of physical function improvement over time while on therapy. At the baseline survey, improvements were reported during pexidartinib treatment with a mean (SD) change of -3.2 (3.1) in worst stiffness NRS and -3.0 (2.7) in worst pain NRS when compared with that prior to pexidartinib treatment (Table 1). Results were sustained between the baseline and follow up, with a mean (SD) change of worst stiffness NRS of 0.8 (2.67) and a mean (SD) change of worst pain NRS of -0.1 (2.09); neither was significant (Table 2). The only TSQM metric that changed significantly over time was the TSQM Effectiveness Domain, of which the mean (SD) was 68.64 (19.167) at baseline and 73.75 (17.749) in the follow up, an average paired increase of 7.28 (19.021) (p-value=0.04) (Table 2). In the follow up, at least 71% of respondents indicated that they had only slight or no problems at each of the five domains of the EQ-5D-5L (Table 3). And majority (85.7%) of patients reported improved overall symptoms since the start of the study (Table 4).

Conclusion: In this study, most TGCT patients reported symptom improvement in physical function, stiffness and pain during pexidartinib treatment than prior to pexidartinib treatment at baseline. After an additional year of follow up, the PROs of physical function, worst stiffness, worst pain, and treatment satisfaction were sustained. The findings suggest longer-term benefits for patients continuing treatment with pexidartinib. Outcomes for patients who discontinued pexidartinib should be evaluated in future studies.