{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:49:37Z","timestamp":1791564577123,"version":"4.3.4"},"reference-count":32,"publisher":"Bioscientifica","issue":"5","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are rare, aggressive malignancies with limited treatment options. Although targeted therapies for tumours harbouring BRAF V600E mutations or fusions involving NTRK1, NTRK2, NTRK3 or RET have expanded treatment options, most patients lack such actionable alterations and urgently require alternative therapeutic strategies. Immune checkpoint blockade (ICB) has emerged as a promising approach, but its real-world application is limited by restricted trial access, reimbursement challenges and the aggressive course of these diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analysed the Essen ATC\/PDTC cohort (June 2018 to February 2024) to evaluate the real-world efficacy of lenvatinib plus pembrolizumab (LEN-PEM) in heavily pretreated patients, including PDTC cases progressing after two or more prior tyrosine kinase inhibitors and ATC cases treated with upfront (radio-)chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the five patients with PDTC, four achieved a partial response and one achieved durable stable disease (&amp;gt;50 months), corresponding to an objective response rate (ORR) of 4\/5 and a clinical benefit rate (CBR) of 5\/5. Median progression-free survival (PFS) and overall survival (OS) from LEN-PEM initiation were 29.1 and 34.9 months, respectively; median OS from diagnosis was not reached. Among the ten patients with ATC, four achieved a partial response and three achieved stable disease, corresponding to an ORR of 4\/10 and a CBR of 7\/10. Median PFS and OS from LEN-PEM initiation were 7.6 and 9.9 months, respectively, and median OS from diagnosis was 24.3 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LEN-PEM demonstrates meaningful clinical activity in pretreated PDTC and ATC patients, supporting its use as a later-line therapeutic option.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/etj-26-0053","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:21:34Z","timestamp":1790616094000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":0,"title":["Clinical outcomes of pembrolizumab combination therapy in heavily pretreated PDTC and anaplastic thyroid cancer"],"prefix":"10.1530","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2904-4341","authenticated-orcid":true,"given":"Tim","family":"Brandenburg","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen 1 , ,","place":["Essen, Germany"]},{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara Maria","family":"Machlah","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen 1 , ,","place":["Essen, Germany"]},{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn Marlene","family":"Srasra","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen 1 , ,","place":["Essen, Germany"]},{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Muchalla","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen 1 , ,","place":["Essen, Germany"]},{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Theurer","sequence":"additional","affiliation":[{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]},{"name":"Institute of Pathology, University Hospital Essen, University Duisburg-Essen 3 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kersting","sequence":"additional","affiliation":[{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]},{"name":"Clinic for Nuclear Medicine, University Hospital Essen, University Duisburg-Essen 4 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel Maria","family":"Weber","sequence":"additional","affiliation":[{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]},{"name":"Clinic for Nuclear Medicine, University Hospital Essen, University Duisburg-Essen 4 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Weber","sequence":"additional","affiliation":[{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]},{"name":"Department of General, Visceral and Transplantation Surgery, Division of Endocrine Surgery, University of Duisburg-Essen 5 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Dralle","sequence":"additional","affiliation":[{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]},{"name":"Department of General, Visceral and Transplantation Surgery, Division of Endocrine Surgery, University of Duisburg-Essen 5 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Lahner","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen 1 , ,","place":["Essen, Germany"]},{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"F\u00fchrer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen 1 , ,","place":["Essen, Germany"]},{"name":"Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen 2 , ,","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"2026100911511045200_bib1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1089\/thy.2020.0944","article-title":"2021 American Thyroid Association Guidelines for management of patients with anaplastic thyroid cancer","volume":"31","author":"Bible","year":"2021","journal-title":"Thyroid"},{"key":"2026100911511045200_bib2","doi-asserted-by":"crossref","DOI":"10.1530\/ERC-22-0293","article-title":"The 2022 WHO classification of thyroid tumors: novel concepts in nomenclature and grading","volume":"30","author":"Christofer Juhlin","year":"2023","journal-title":"Endocr Relat Cancer"},{"key":"2026100911511045200_bib3","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1001\/jamaoncol.2020.3362","article-title":"Evaluation of overall survival in patients with anaplastic thyroid carcinoma, 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