{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T15:32:41Z","timestamp":1793287961405,"version":"4.5.0"},"reference-count":30,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      wild-type anaplastic thyroid carcinomas (\n                      <jats:italic toggle=\"yes\">\n                        BRAF\n                        <jats:sup>WT<\/jats:sup>\n                      <\/jats:italic>\n                      -ATCs) have a poor prognosis, in part, due to limited effective therapies. The preliminary results from the phase II ATLEP trial suggest the promising clinical activity of lenvatinib plus pembrolizumab (L\/P). We aimed to confirm the real-world efficacy of L\/P in\n                      <jats:italic toggle=\"yes\">\n                        BRAF\n                        <jats:sup>WT<\/jats:sup>\n                      <\/jats:italic>\n                      -ATC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      A retrospective single-center study of patients with\n                      <jats:italic toggle=\"yes\">\n                        BRAF\n                        <jats:sup>WT<\/jats:sup>\n                      <\/jats:italic>\n                      -ATC treated with first-line L\/P between January 2016 and July 2024 outside of a clinical trial. The primary endpoints were confirmed overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In 36 eligible patients, the median age at treatment start was 64 years (range, 41\u201384 years). All patients had distant metastases, and 46% had radiological suspicion of locoregional invasion, including that of the trachea, esophagus, and\/or internal jugular vein. The most common driver mutations were\n                      <jats:italic toggle=\"yes\">RAS<\/jats:italic>\n                      (39%) and\n                      <jats:italic toggle=\"yes\">NF1<\/jats:italic>\n                      (19%); 61% had co-occurring\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      and 50%\n                      <jats:italic toggle=\"yes\">TERT<\/jats:italic>\n                      promoter mutations. In the evaluated specimens, programmed cell death ligand 1 (PD-L1) combined positive score was \u22651 in 96% (27\/28), median tumor mutational burden was 2 mut\/Mb (interquartile range [IQR], 1-4), and high microsatellite instability (MSI-H) was present in 7% (2\/30). Previous therapies for ATC included surgery (69%), definitive- (31%) or palliative-intent (31%) neck external beam radiation, and cytotoxic chemotherapy (9%). The median initial lenvatinib dose was 16 mg (IQR, 10\u201320 mg). Pembrolizumab dosing was 200 mg Q3 weeks (64%) or 400 mg Q6 weeks (36%). The median time between lenvatinib and pembrolizumab initiation was 0.5 days (IQR, \u22127.8 to 10.5). With a median follow-up of 39.5 months [confidence interval {CI}, 8.1\u201354.3], the median OS was 7.7 months [CI, 4.6\u201322.9], and the median PFS was 6.2 months [CI, 3.1\u20137.9]. In 33\/36 patients evaluable for responses, the confirmed ORR was 36%, and the median duration of the response was 16.0 months [CI, 3.2\u201328.8]. The best overall response was confirmed complete response in 3 (9%), confirmed partial response in 9 (28%), stable disease in 11 (33%), and progressive disease in 10 (30%) patients. The safety profile was similar to previous studies. Five (14%) patients stopped pembrolizumab due to immune-related toxicity, including pneumonitis (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 2) and colitis (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 3). Two patients discontinued lenvatinib due to concern for esophageal or tracheal fistula; however, no further intervention was required in either case.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Our real-world experience with L\/P in metastatic\n                      <jats:italic toggle=\"yes\">\n                        BRAF\n                        <jats:sup>WT<\/jats:sup>\n                      <\/jats:italic>\n                      -ATC demonstrates the clinical efficacy and safety of this combination, consistent with prior reports. A prospective clinical trial in the United States is ongoing (NCT#04171622).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10507256251409138","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T14:36:01Z","timestamp":1767796561000},"page":"153-161","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Real-World Experience with Lenvatinib plus Pembrolizumab in Metastatic\n                    <i>BRAF<\/i>\n                    Wild-Type Anaplastic Thyroid Carcinoma"],"prefix":"10.1177","volume":"36","author":[{"given":"Sarah","family":"Hamidi","sequence":"first","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danica M.","family":"Vodopivec","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, The University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naifa L.","family":"Busaidy","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gule-Monroe","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal S.","family":"Akhave","sequence":"additional","affiliation":[{"name":"Department of Thoracic-Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria E.","family":"Banuchi","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Ferraroto","sequence":"additional","affiliation":[{"name":"Department of Thoracic-Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Fournier","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Brandon","family":"Gunn","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka C.","family":"Iyer","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Maniakas","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente R.","family":"Marczyk","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana G.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Thoracic-Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micheal T.","family":"Spiotto","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Waguespack","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Zafereo","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Cabanillas","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia 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