A phase 4, multicenter, global clinical study to evaluate discontinuation and rechallenge of pexidartinib in patients with tenosynovial giant cell tumor previously treated with pexidartinib
Cancer, vol. 131, pp. e35634
Abstract
BACKGROUND: Pexidartinib is effective in patients with tenosynovial giant cell tumor (TGCT) for whom surgery is not feasible. Durability of response after discontinuation of pexidartinib and the safety and efficacy of restarting pexidartinib have not been previously recorded. This phase 4 study was designed to mimic the real-world experience with pexidartinib to evaluate the effects of discontinuation of and retreatment with pexidartinib in patients with TGCT who previously benefited from the drug. METHODS: This was a global, multicenter, phase 4 study that enrolled patients with TGCT who were experiencing clinical benefit from pexidartinib in one of four prior phase 1 or phase 3 studies investigating pexidartinib in the disease. Patients could choose to continue pexidartinib at the same dose (the treatment-continuation cohort) or discontinue treatment with the option to restart pexidartinib (the treatment-free/retreatment cohort). Tumor progression determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, patient-reported outcomes (the Patient-Reported Outcomes Measurement Information System-Physical Function [PROMIS-PF] questionnaire and the EuroQol 5-dimension, 5-level [EQ-5D-5L] visual analog scale), and safety were assessed every 3 months. The primary end point was the proportion of patients in the treatment-free/retreatment cohort who remained treatment-free at month 12 and 24; this did not depend on disease progression. RESULTS: Thirty-two patients were enrolled: 21 chose to enter the treatment-continuation cohort, and 11 entered the treatment-free/retreatment cohort. During the treatment-free period, six of 11 (54.5%) patients in the treatment-free/retreatment cohort had progressive disease (PD) according to RECIST, version 1.1, whereas no patient in the treatment-continuation cohort had disease progression. Over the 24-month study, three of 11 (27.3%) patients in the treatment-free/retreatment cohort restarted treatment because of RECIST version 1.1 PD, symptomatic progression, or both (n = 1 each). The probability of remaining treatment-free in the treatment-free/retreatment cohort was 73% (95% confidence interval, 37%-90%). In the treatment-free/retreatment cohort, the median progression-free survival of the treatment-free period was 22.8 months (95% confidence interval, 1.6 months to not estimable). By 6 months of retreatment, all retreated patients achieved new disease stabilization with no new safety concerns; two patients had clinically significant improvements in PROMIS-PF and EQ-5D-5L visual analog scale scores. The mean PROMIS-PF and EQ-5D-5L scores remained stable throughout the study. There was no hepatotoxicity and no new safety signal in either cohort. CONCLUSIONS: In this small phase 4 study designed to evaluate outcomes in patients who stopped and restarted pexidartinib, 54.5% of patients who discontinued pexidartinib showed PD, with a median progression-free survival of 22.8 months. Each of the three patients who restarted pexidartinib stopped progressing, and some reported a new gain in physical function. No PD was detected in patients who remained on treatment, and the safety profile did not indicate long-term hepatotoxicity or any new safety concerns. PLAIN LANGUAGE SUMMARY: Pexidartinib is a medication for people with tenosynovial giant cell tumor (TGCT) for whom surgery is not recommended. This study examined what happens when patients stop taking pexidartinib (after it has helped them) to see whether it is safe and effective to restart if needed. Thirty-two patients were followed for 2 years: 21 chose to continue pexidartinib and did not experience disease progression, while 11 chose to stop pexidartinib; 54.5% of them had disease progression within 2 years. Three patients who stopped pexidartinib restarted treatment after their tumor size increased or their symptoms worsened. Restarting pexidartinib was safe and effective in these patients.
Authors 17
-
The Royal Melbourne Hospital · Peter MacCallum Cancer Centre
Affiliation as printed
Royal Melbourne Hospital and Peter MacCallum Cancer Centre Melbourne Victoria Australia
Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
-
Affiliation as printed
Dana‐Farber Cancer Institute Center for Sarcoma and Bone Oncology Boston Massachusetts USA
Dana-Farber Cancer Institute, Center for Sarcoma and Bone Oncology, Boston, Massachusetts, USA
-
Hospital Universitario Virgen del Rocío
Affiliation as printed
Virgen del Rocio University Hospital Seville Spain
Virgen del Rocio University Hospital, Seville, Spain
-
Affiliation as printed
Rizzoli Orthopedic Institute Bologna Italy
Rizzoli Orthopedic Institute, Bologna, Italy
-
National Taiwan University Hospital
Affiliation as printed
National Taiwan University Hospital Taipei Taiwan
National Taiwan University Hospital, Taipei, Taiwan
-
Affiliation as printed
Semmelweis University Budapest Hungary
Semmelweis University, Budapest, Hungary
-
Oregon Health & Science University
Affiliation as printed
Oregon Health & Science University Portland Oregon USA
Oregon Health & Science University Portland Oregon USA
-
Memorial Sloan Kettering Cancer Center
Affiliation as printed
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College New York New York USA
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA
-
University of Miami Health System · Sylvester Comprehensive Cancer Center
Affiliation as printed
Sylvester Comprehensive Cancer Center University of Miami Health System Miami Florida USA
Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida, USA
-
Hans A. J. Gelderblom Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center Leiden Netherlands
Leiden University Medical Center, Leiden, Netherlands
-
Affiliation as printed
Chris O’Brien Lifehouse Sydney New South Wales Australia
Chris O'Brien Lifehouse, Sydney, New South Wales, Australia
-
Affiliation as printed
Hospital of the Holy Cross and Saint Paul Barcelona Spain
Hospital of the Holy Cross and Saint Paul, Barcelona, Spain
-
Washington University in St. Louis · Alvin J. Siteman Cancer Center
Affiliation as printed
Siteman Cancer Center and Washington University School of Medicine St Louis Missouri USA
Siteman Cancer Center and Washington University School of Medicine, St Louis, Missouri, USA
-
Daiichi Sankyo (United States)
Affiliation as printed
Daiichi Sankyo, Inc. Basking Ridge New Jersey USA
Daiichi Sankyo, Inc., Basking Ridge, New Jersey, USA
-
Daiichi Sankyo (United States)
Affiliation as printed
Daiichi Sankyo, Inc. Basking Ridge New Jersey USA
Daiichi Sankyo, Inc., Basking Ridge, New Jersey, USA
-
Daiichi Sankyo (United States)
Affiliation as printed
Daiichi Sankyo, Inc. Basking Ridge New Jersey USA
Daiichi Sankyo, Inc., Basking Ridge, New Jersey, USA
-
Silvia Stacchiotti corresponding
Fondazione IRCCS Istituto Nazionale dei Tumori
Affiliation as printed
Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Cited by 10 stored of 10
10 results
No patents citing this paper on Lens.org (checked 2026-10-11).