Abstract
e18236 Background: The double-blind, randomized, placebo-controlled phase 3 ENLIVEN study in TGCT demonstrated a significant tumor response at week 25 by RECIST for pexidartinib (39% vs. 0% for placebo) and improvement in joint function and symptoms. The aim of this analysis was to identify a threshold score for responder definitions for PROMIS-PF scale and Worst Stiffness Numerical Rating Scale (WS-NRS) and compared responder rates for pexidartinib versus placebo. Methods: Anchor- and distribution-based estimates were calculated, and cumulative distribution function (CDF) plots were generated to derive responder definition threshold estimates. Anchor- and distribution-based results and CDFs were evaluated through triangulation, following FDA PRO Guidance, to determine a single responder definition threshold (i.e., meaningful change) for each instrument. The proportion of responders at Week 25 between treatments was compared with Fisher’s Exact Test (2-sided). Results: 120 patients were randomized to pexidartinib (n = 61) and placebo (n = 59) and assessed through 25 weeks of treatment. Anchor-based analysis showed one-level improvement on the patient global rating of PF item was associated with a mean change of 4.0 on PROMIS-PF. Distribution-based estimates (0.5 SD and 1 SEM) for PROMIS-PF were 2.8 and 2.5, respectively. For WS-NRS, a response of “A little improved” by patients on the perception of stiffness item was associated with a mean change of 1.1. The distribution-based estimates for the WS-NRS item were 0.9 and 0.5, respectively. This resulted in the following responder definition thresholds: ≥3 points for PROMIS-PF and ≥1 for WS-NRS improvement. A greater proportion of pexidartinib as compared to placebo patients were responders by PROMIS-PF (30% vs. 5%, p < 0.001) and WS-NRS (39% vs. 19%, p = 0.02) at week 25, respectively. Conclusions: Triangulation yielded responder definitions of ≥3 points for PROMIS-PF and ≥1 for WS-NRS. With these definitions, a greater proportion of patients treated with pexidartinib compared to placebo had meaningful improvement in physical function and stiffness.
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