Abstract
Background and purpose — The ENLIVEN trial showed that, after 25 weeks, pexidartinib statistically significantly reduced tumor size more than placebo in patients with symptomatic, advanced tenosynovial giant cell tumor (TGCT) for whom surgery was not recommended. Here, we detail the effect of pexidartinib on patient-reported physical function and stiffness in ENLIVEN. Patients and methods — This was a planned analysis of patient-reported outcome data from ENLIVEN, a double-blinded, randomized phase 3 trial of adults with symptomatic, advanced TGCT treated with pexidartinib or placebo. Physical function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS)-physical function (PF), and worst stiffness was assessed using a numerical rating scale (NRS). A mixed model for repeated measures was used to compare changes in PROMIS-PF and worst stiffness NRS scores from baseline to week 25 between treatment groups. Response rates for the PROMIS-PF and worst stiffness NRS at week 25 were calculated based on threshold estimates from reliable change index and anchor-based methods. Results — Between baseline and week 25, greater improvements in physical function and stiffness were experienced by patients receiving pexidartinib than patients receiving placebo (change in PROMIS-PF = 4.1 [95% confidence interval (CI) 1.8–6.3] vs. –0.9 [CI −3.0 to 1.2]; change in worst stiffness NRS = –2.5 [CI −3.0 to −1.9] vs. –0.3 [CI −0.9 to 0.3]). Patients receiving pexidartinib had higher response rates than patients receiving placebo for meaningful improvements in physical function and stiffness. Improvements were sustained after 50 weeks of pexidartinib treatment. Interpretation — Pexidartinib treatment provided sustained, meaningful improvements in physical function and stiffness for patients with symptomatic, advanced TGCT.
Highlights
Patients and methods — This was a planned analysis of patient-reported outcome data from ENLIVEN, a doubleblinded, randomized phase 3 trial of adults with symptomatic, advanced tenosynovial giant cell tumor (TGCT) treated with pexidartinib or placebo
Pexidartinib is an inhibitor of the colony-stimulating factor1, KIT, and FLT3 receptor tyrosine kinases that was approved by the US Food and Drug Administration (FDA) for the treatment of adults with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery (Lamb 2019)
The secondary endpoints in ENLIVEN were comparative analyses at week 25 of the (1) mean change from baseline in the range of motion of the affected joint; (2) the proportion of responders based on centrally evaluated MRI scans and tumor volume score (TVS); (3) mean change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-physical function (PF); (4) mean change from baseline in worst stiffness numerical rating scale (NRS); (5) proportion of responders based on the Brief Pain Inventory worst pain NRS and analgesic use by the Brief Pain Inventory-30 definition; and
Summary
Patients and methods — This was a planned analysis of patient-reported outcome data from ENLIVEN, a doubleblinded, randomized phase 3 trial of adults with symptomatic, advanced TGCT treated with pexidartinib or placebo. Patients receiving pexidartinib had higher response rates than patients receiving placebo for meaningful improvements in physical function and stiffness. Interpretation — Pexidartinib treatment provided sustained, meaningful improvements in physical function and stiffness for patients with symptomatic, advanced TGCT. Pexidartinib is an inhibitor of the colony-stimulating factor, KIT, and FLT3 receptor tyrosine kinases that was approved by the US Food and Drug Administration (FDA) for the treatment of adults with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery (Lamb 2019). In ENLIVEN, a randomized, placebo-controlled phase 3 trial in 120 patients with symptomatic, advanced TGCT for whom surgery was not rec-
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