{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:39:40Z","timestamp":1790710780496,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":140,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Assistance Publique\u2014H\u00f4pitaux de Paris"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oncogenic FGFR\u2013TACC fusions are present in 3\u20135% of high-grade gliomas (HGGs). Fexagratinib (AZD4547) is an oral FGFR1\u20133 inhibitor with preclinical activity in FGFR\u2013TACC+ gliomas. We tested its safety and efficacy in patients with recurrent FGFR\u2013TACC\u2005+\u2005HGGs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>TARGET (NCT02824133) is a phase I\/II open-label multicenter study that included adult patients with FGFR\u2013TACC\u2005+\u2005HGGs relapsing after \u22651 line of standard chemoradiation. Patients received fexagratinib 80\u00a0mg bd on a continuous schedule until disease progression or unacceptable toxicity. The primary endpoint was the 6-month progression-free survival rate (PFS6).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twelve patients with recurrent IDH wildtype FGFR\u2013TACC\u2005+\u2005HGGs (all FGFR3\u2013TACC3+) were included in the efficacy cohort (male\/female ratio\u2005=\u20051.4, median age\u2005=\u200561.5 years). Most patients (67%) were included at the first relapse. The PFS6 was 25% (95% confidence interval 5\u201357%), with a median PFS of 1.4 months. All patients without progression at 6 months (n\u2005=\u20053) were treated at first recurrence (versus 56% of those in progression) and remained progression-free for 14\u201323 months. The best response was RANO partial response in 1 patient (8%), stable disease in 5 (42%), and progressive disease in 6 (50%). Median survival was 17.5 months from inclusion. Grade 3 toxicities included lymphopenia, hyperglycaemia, stomatitis, nail changes, and alanine aminotransferase increase (n\u2005=\u20051 each). No grade 4\u20135 toxicities were seen. A 32-gene signature was associated with the benefit of FGFR inhibition in FGFR3\u2013TACC3\u2005+\u2005HGGs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Fexagratinib exhibited acceptable toxicity but limited efficacy in recurrent FGFR3\u2013TACC3\u2005+\u2005HGGs. Patients treated at first recurrence appeared more likely to benefit, yet additional evidence is required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/noajnl\/vdae068","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T16:42:13Z","timestamp":1715877733000},"source":"Crossref","is-referenced-by-count":9,"title":["TARGET: A phase I\/II open-label multicenter study to assess safety and efficacy of fexagratinib in patients with relapsed\/refractory FGFR fusion-positive glioma"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7807-5393","authenticated-orcid":false,"given":"Alberto","family":"Picca","sequence":"first","affiliation":[{"name":"Service de Neuro-Oncologie, Institut de Neurologie, DMU Neurosciences, AP-HP, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re , Paris, France"},{"name":"Sorbonne Universit\u00e9, Inserm, CNRS, UMR S 1127, Paris Brain Institute (ICM) , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Luisa","family":"Di Stefano","sequence":"additional","affiliation":[{"name":"Department of Neurology, Foch Hospital , Suresnes , France"},{"name":"Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest , Livorno , Italy"},{"name":"Sorbonne Universit\u00e9, Inserm, CNRS, UMR S 1127, Paris Brain Institute (ICM) , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Savatovsky","sequence":"additional","affiliation":[{"name":"Department of Radiology, H\u00f4pital Fondation A. de Rothschild , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Ducray","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, East Group Hospital, Hospices Civils de Lyon , Lyon , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Chinot","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, AP-HM, University Hospital Timone , Marseille , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth Cohen-Jonathan","family":"Moyal","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Claudius Regaud Institute, Cancer University Institute of Toulouse, Oncopole 1, Paul Sabatier University , Toulouse III, Toulouse , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paule","family":"Augereau","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institut de Canc\u00e9rologie de L\u2019ouest- Paul Papin , Angers , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9408-3278","authenticated-orcid":false,"given":"Emilie","family":"Le 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