OBJECTIVES: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm that involves the synovium, bursae, or tendon sheath. Tumor location varies and is often associated with joint destruction, pain, stiffness, and limited range of motion (ROM). The objective of the current analysis was to define a meaningful change in clinical outcome assessments (COAs) measuring active range of motion, physical function and stiffness among patients with TGCT.

METHODS: Qualitative embedded exit interviews were conducted with patients participating in the double-blind MOTION Phase 3 trial (NCT05059262) of vimseltinib vs placebo for TGCT. Patients were asked about meaningful changes in Patient Global Impression of Change (PGIC) and Patient Global Impression of Severity (PGIS) anchors, active ROM, physical function (Patient-Reported Outcomes Measurement Information System (PROMIS) – Physical Function (PF)), and stiffness (Worst Stiffness Numeric Rating Scale (NRS)). Subsequent quantitative anchor (using PGIS and PGIC) and distribution-based analyses of the clinical trial data, informed by the results of the qualitative interviews, were used to triangulate and define meaningful within-patient changes. Analyses were conducted on blinded data prior to trial primary analyses.

RESULTS: A total of 123 patients were randomized in MOTION with 96 (78%) completing an exit interview. The PGIC anchor variables had moderate correlations with changes in the COA measures (range: |0.38 to 0.54|). The data for both the PGIC-PF and PGIC-ROM support that most patients (PGIC-PF: 67%; PGIC-ROM 73%) considered “minimally improved” responses on these questions to represent clinically meaningful changes. Anchor- and distribution-based estimates for PROMIS-PF ranged from 1.45 to 4.9, for active ROM from 6.0 to 16.4, and Worst Stiffness from -2.3 to -0.5.

CONCLUSIONS: Combined evidence from anchor and distribution-based methods supported by patient insights from qualitative interviews informed the final selection of MCIDs of +3-points for PROMIS-PF, +10% for active ROM, and -2-points for Worst Stiffness NRS.