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

Acta Orthopaedica, vol. 92, pp. 493–499

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.

Authors 15

1. Michiel A. J. van de Sande Aachen Department of Orthopedics, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Orthopedics, Leiden University Medical Center, Leiden, the Netherlands

2. William D. Tap

   Memorial Sloan Kettering Cancer Center

   Affiliation as printed

   Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA

3. Heather L. Gelhorn
   Affiliation as printed

   Department of Patient-Centered Research, Evidera, Bethesda, MD, USA

4. Xin Ye

   Daiichi Sankyo (United States)

   Affiliation as printed

   Department of Global Health Economics and Outcomes Research, Daiichi Sankyo Inc, Basking Ridge, NJ, USA

5. Rebecca M. Speck
   Affiliation as printed

   Department of Patient-Centered Research, Evidera, Bethesda, MD, USA

6. Emanuela Palmerini

   Istituto Ortopedico Rizzoli

   Affiliation as printed

   Department of Experimental, Diagnostic, and Specialty Medicine, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

7. Silvia Stacchiotti

   Fondazione IRCCS Istituto Nazionale dei Tumori

   Affiliation as printed

   Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

8. Jayesh Desai

   Peter MacCallum Cancer Centre

   Affiliation as printed

   Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

9. Andrew J. Wagner

   Dana-Farber Cancer Institute

   Affiliation as printed

   Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

10. Thierry Alcindor

    McGill University

    Affiliation as printed

    Department of Medical Oncology, McGill University, Montreal, Quebec, Canada

11. Kristen N. Ganjoo

    Stanford Cancer Institute · Stanford University

    Affiliation as printed

    Department of Medical Oncology, Stanford Cancer Institute, Stanford, CA, USA

12. Javier Martín‐Broto

    Instituto de Biomedicina de Sevilla · Hospital Universitario Virgen del Rocío · Universidad de Sevilla

    Affiliation as printed

    Department of Medical Oncology, University Hospital Virgen del Rocio and Institute of Biomedicine of Sevilla (IBIS) (HUVR, CSIC, University of Sevilla), Seville, Spain

13. Dale Edward Shuster

    Daiichi Sankyo (United States)

    Affiliation as printed

    Department of Global Clinical Oncology Research and Development, Daiichi Sankyo Inc, Basking Ridge, NJ, USA

14. Hans A. J. Gelderblom Aachen Department of Medical Oncology

    Leiden University Medical Center

    Affiliation as printed

    Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands

15. John H. Healey

    Memorial Sloan Kettering Cancer Center

    Affiliation as printed

    Department of Orthopaedic Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA