Pexidartinib improves physical functioning and stiffness in patients with tenosynovial giant cell tumor: results from the ENLIVEN randomized clinical trial

Michiel  van de Sande; William D Tap; Heather L Gelhorn; Xin Ye; Rebecca M  Speck; Emanuela Palmerini; Silvia Stacchiotti; Jayesh Desai; Andrew J Wagner; Thierry Alcindor; Kristen Ganjoo; Javier  Martín-Broto; Qiang  Wang; Dale Shuster; Hans Gelderblom; John H Healey

doi:10.1080/17453674.2021.1922161

Authors

Michiel van de Sande Department of Orthopedics, Leiden University Medical Center, Leiden, the Netherlands
William D Tap Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA
Heather L Gelhorn Department of Patient-Centered Research, Evidera, Bethesda, MD, USA
Xin Ye Department of Global Health Economics and Outcomes Research, Daiichi Sankyo Inc, Basking Ridge, NJ, USA
Rebecca M Speck Department of Patient-Centered Research, Evidera, Bethesda, MD, USA
Emanuela Palmerini Department of Experimental, Diagnostic, and Specialty Medicine, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
Silvia Stacchiotti Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Jayesh Desai Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Andrew J Wagner Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Thierry Alcindor Department of Medical Oncology, McGill University, Montreal, Quebec, Canada
Kristen Ganjoo Department of Medical Oncology, Stanford Cancer Institute, Stanford, CA, USA
Javier Martín-Broto Department of Medical Oncology, University Hospital Virgen del Rocio and Institute of Biomedicine of Sevilla (IBIS) (HUVR, CSIC, University of Sevilla), Seville, Spain
Qiang Wang Department of Biostatistics and Data Management, Daiichi Sankyo Inc, Basking Ridge, NJ, USA
Dale Shuster Department of Global Clinical Oncology Research and Development, Daiichi Sankyo Inc, Basking Ridge, NJ, USA
Hans Gelderblom Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
John H Healey Department of Orthopaedic Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA

DOI:

https://doi.org/10.1080/17453674.2021.1922161

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 doubleblinded, 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.