{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:56:30Z","timestamp":1789721790911,"version":"4.0.1"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002973","name":"Daiichi-Sankyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002973","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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\u2010world experience with pexidartinib to evaluate the effects of discontinuation of and retreatment with pexidartinib in patients with TGCT who previously benefited from the drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 <jats:italic>treatment\u2010continuation cohort<\/jats:italic>) or discontinue treatment with the option to restart pexidartinib (the <jats:italic>treatment\u2010free\/retreatment cohor<\/jats:italic>t). Tumor progression determined by Response Evaluation Criteria\u00a0in Solid Tumors (RECIST) version 1.1, patient\u2010reported outcomes (the Patient\u2010Reported Outcomes Measurement Information System\u2013Physical Function [PROMIS\u2010PF] questionnaire and the EuroQol 5\u2010dimension, 5\u2010level [EQ\u20105D\u20105L] visual analog scale), and safety were assessed every 3 months. The primary end point was the proportion of patients in the treatment\u2010free\/retreatment cohort who remained treatment\u2010free at month 12 and 24; this did not depend on disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010two patients were enrolled: 21 chose to enter the <jats:italic>treatment\u2010continuation cohort<\/jats:italic>, and 11 entered the <jats:italic>treatment\u2010free\/retreatment cohort<\/jats:italic>. During the treatment\u2010free period, six of 11 (54.5%) patients in the treatment\u2010free\/retreatment cohort had progressive disease (PD) according to RECIST, version 1.1, whereas no patient in the treatment\u2010continuation cohort had disease progression. Over the 24\u2010month study, three of 11 (27.3%) patients in the treatment\u2010free\/retreatment cohort restarted treatment because of RECIST version 1.1 PD, symptomatic progression, or both (<jats:italic>n<\/jats:italic>\u00a0=\u00a01 each). The probability of remaining treatment\u2010free in the treatment\u2010free\/retreatment cohort was 73% (95% confidence interval, 37%\u201390%). In the treatment\u2010free\/retreatment cohort, the median progression\u2010free survival of the treatment\u2010free 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\u2010PF and EQ\u20105D\u20105L visual analog scale scores. The mean PROMIS\u2010PF and EQ\u20105D\u20105L scores remained stable throughout the study. There was no hepatotoxicity and no new safety signal in either cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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\u2010free 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\u2010term hepatotoxicity or any new safety concerns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Pexidartinib is a medication for people with tenosynovial giant cell tumor (TGCT) for whom surgery is not recommended.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>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.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Thirty\u2010two 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.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Three patients who stopped pexidartinib restarted treatment after their tumor size increased or their symptoms worsened.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Restarting pexidartinib was safe and effective in these patients.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35634","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T07:23:58Z","timestamp":1731482638000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["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"],"prefix":"10.1002","volume":"131","author":[{"given":"Jayesh","family":"Desai","sequence":"first","affiliation":[{"name":"Royal Melbourne Hospital and Peter MacCallum Cancer Centre  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4384-9448","authenticated-orcid":false,"given":"Andrew J.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute Center for Sarcoma and Bone Oncology  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Carrasco Garcia","sequence":"additional","affiliation":[{"name":"Virgen del Rocio University Hospital  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Cesari","sequence":"additional","affiliation":[{"name":"Rizzoli Orthopedic Institute  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gordon","sequence":"additional","affiliation":[{"name":"HonorHealth Research Institute  Scottsdale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Chi","family":"Lin","sequence":"additional","affiliation":[{"name":"National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Papai","sequence":"additional","affiliation":[{"name":"Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Tap","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan C.","family":"Trent","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center University of Miami Health System  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-8636","authenticated-orcid":false,"given":"Hans","family":"Gelderblom","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Grimison","sequence":"additional","affiliation":[{"name":"Chris O\u2019Brien Lifehouse  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"L\u00f3pez Pousa","sequence":"additional","affiliation":[{"name":"Hospital of the Holy Cross and Saint Paul  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4572-6668","authenticated-orcid":false,"given":"Brian A.","family":"Van Tine","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center and Washington University School of Medicine  St\u00a0Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rubinacci","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo, Inc.  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