(P 37) HEALTH-RELATED QUALITY OF LIFE FROM A PHASE 4 STUDY TO EVALUATE DISCONTINUATION AND RECHALLENGE OF PEXIDARTINIB IN PATIENTS WITH TENOSYNOVIAL GIANT CELL TUMOR PREVIOUSLY TREATED WITH PEXIDARTINIB

Objective: Tenosynovial giant cell tumor (TGCT) is a rare, nonmalignant neoplasm of the synovium, bursae, or tendon sheath and has a median onset age of 40 years. Pexidartinib, the only systemic therapy indicated for treatment of adults with TGCT with severe morbidity/functional limitations not amenable to surgical improvement, has demonstrated robust TGCT tumor responses and improved functional outcomes (FDA-approved in 2019). Since the pivotal ENLIVEN trial, interest emerged regarding the feasibility and impact of intermittent dosing. Hence, this phase 4, global, open-label, non-randomized study (NCT04526704) was designed to examine TGCT patients previously treated with pexidartinib during treatment and discontinuation/rechallenge with pexidartinib. Due to the early onset of TGCT and the established associated deterioration of health-related quality of life (HRQOL), this analysis focuses on HRQOL over time during treatment and discontinuation/rechallenge with pexidartinib.

Methods: Patients with TGCT who were actively enrolled in one of four pexidartinib trials (NCT02371369; NCT01004861; NCT02734433; NCT03291288) in the US, Europe, Australia, and Taiwan enrolled after the previous trial’s end-of-treatment (EOT) visit. Patients had the choice to continue pexidartinib (Treatment Continuation Cohort [TCC]) at their current dose or discontinue pexidartinib with the option to re-initiate (Treatment-Free/Re-Treatment Cohort [TF/RTC]) at the investigator’s and patient’s discretion; treatment would be resumed at the same dose level received at the prior EOT visit. Patients in the TCC underwent assessments at 3-month intervals. Patients in the TF/RTC underwent initial assessments at 1- and 3-months, then 3-month intervals thereafter. This analysis reports on the secondary endpoints of change from baseline in patient-reported outcomes (PROMIS physical function [PF], EQ-5D-5L Visual Analog Scale [VAS]) in the TCC and TF/RTC.

Results: From October 2020-April 2021, 32 patients enrolled (21 in TCC, 11 in TF/RTC). Patients had a median age of 47.5 (range: 21-81) years, median of 7.8 (4.6-32.6) years from diagnosis to informed consent, and median of 55.7 (26.7-91.0) months of prior pexidartinib treatment. In the TCC, the 24-month average paired change (APC) from baseline was -2.78 (95% confidence interval: -6.20, 0.65) and -2.4 (-9.6, 4.8) for PROMIS PF and EQ-5D-5L VAS, respectively. During the TF period, the 24-month APC was -1.93 (-6.37, 2.51) and 3.4 (-3.6, 10.4) for PROMIS PF and EQ-5D-5L VAS, respectively. Three of eleven patients in the treatment-free period chose to re-initiate treatment due to symptomatic progression (n=1), tumor progression (n=1), or both (n=1). Two of three patients who re-initiated treatment experienced clinically significant (≥10 point) increases in both PROMIS PF and EQ-5D-5L VAS.

Conclusion: Despite previous literature reporting HRQOL deterioration over time for TGCT patients, HRQOL was generally sustained for these pexidartinib-exposed participants during the approximate 2-year follow-up. Further HRQOL investigations for patients on long-term continuous and intermittent pexidartinib treatment are warranted.