{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:06:24Z","timestamp":1789416384416,"version":"build-2803163510"},"reference-count":34,"publisher":"Bioscientifica","issue":"8","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Larotrectinib is a first-in-class, highly selective, central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for tumour-agnostic use in TRK fusion cancer. It has previously demonstrated rapid and durable disease control and favourable safety in patients with advanced TRK fusion thyroid carcinoma (TC). After an additional 4 years of follow-up with the inclusion of two additional patients, and utilising an independent review committee (IRC) to assess overall response rate (ORR), we report updated pooled analyses from three phase 1\u20132 larotrectinib clinical trials, focusing only on patients with TRK fusion differentiated TC (DTC). The primary endpoint was the IRC-determined ORR per RECIST v1.1. Duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety were also assessed. Twenty-four patients (papillary TC, n = 21; follicular TC, n = 2; poorly DTC, n = 1) were included (data cut-off: 20 July 2024). ORR was 79% (95% confidence interval (CI): 58\u201393); best responses were complete response in 3 (13%) patients, partial response in 16 (67%), stable disease in 3 (13%), progressive disease in 1 (4%) and not evaluable in 1 (4%). Median DoR and PFS were 35 (95% CI: 22\u2013not estimable (NE)) and 44 (95% CI: 35\u2013NE) months, respectively; 6-year OS rate was 71% (95% CI: 50\u201391). Six patients remained on treatment. Treatment-related adverse events (TRAEs) were mainly grade 1\/2; no patients permanently discontinued treatment due to TRAEs. Larotrectinib continues to demonstrate durable disease control, extended survival and a favourable long-term safety profile in patients with advanced TRK fusion DTC requiring systemic therapy.<\/jats:p>","DOI":"10.1530\/erc-25-0531","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T10:09:36Z","timestamp":1784110176000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":1,"title":["Larotrectinib in TRK fusion differentiated thyroid carcinoma: updated trial data"],"prefix":"10.1530","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0280-0100","authenticated-orcid":true,"given":"Steven G","family":"Waguespack","sequence":"first","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center 1 , , ,","place":["Houston, Texas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7096-4057","authenticated-orcid":true,"given":"Marcia S","family":"Brose","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University Hospital 2 , , ,","place":["Philadelphia, Pennsylvania, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica J","family":"Lin","sequence":"additional","affiliation":[{"name":"Cancer Institute, Mass General Brigham Cancer Institute 3 , , ,","place":["Boston, Massachusetts, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"McDermott","sequence":"additional","affiliation":[{"name":"Department of Oncology, St Vincent\u2019s University Hospital and Cancer Trials Ireland 4 , ,","place":["Dublin, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Almubarak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, West Virginia University 5 , , ,","place":["Morgantown, West Virginia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Bauman","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Fox Chase Cancer Center 6 , , ,","place":["Philadelphia, Pennsylvania, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Casanova","sequence":"additional","affiliation":[{"name":"Paediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori 7 , ,","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivaani","family":"Kummar","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University 8 , , ,","place":["Portland, Oregon, 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Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsong","family":"Qi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute 12 , ,","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"Neu","sequence":"additional","affiliation":[{"name":"Early Development Statistics Department, Evidenze Germany GmbH 13 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domnita-Ileana","family":"Burcoveanu","sequence":"additional","affiliation":[{"name":"Clinical Development of Oncology, Bayer HealthCare Pharmaceuticals, Inc. 14 , ,","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara 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