{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T12:29:22Z","timestamp":1793622562691,"version":"4.5.0"},"reference-count":22,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"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":[[2024,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Lenvatinib and sorafenib are standard of care first-line treatments for advanced, radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC). However, most patients eventually become treatment-resistant and require additional therapies. The phase 3 COSMIC-311 study investigated cabozantinib in patients with RAIR DTC who progressed on lenvatinib, sorafenib, or both and showed that cabozantinib provided substantial clinical benefit. Presented in this study is an analysis of COSMIC-311 based on prior therapy and histology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Patients were randomized 2:1 (stratification: prior lenvatinib [yes\/no]; age [\u226465, &gt;65 years]) to oral cabozantinib (60\u2009mg tablet\/day) or matched placebo. Eligible patients received 1\u20132 prior vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors for DTC (lenvatinib or sorafenib required), had a confirmed DTC diagnosis, and were refractory to or ineligible for radioiodine therapy. For this analysis, progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by a blinded independent radiology committee were evaluated by prior therapy (lenvatinib only, sorafenib only, both) and histology (papillary, follicular, oncocytic, poorly differentiated).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Two hundred fifty-eight patients were randomized (170 cabozantinib\/88 placebo) who previously received sorafenib only (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200996), lenvatinib only (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009102), or both (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200960). The median follow-up was 10.1 months. The median PFS (months) with cabozantinib\/placebo was 16.6\/3.2 (sorafenib only: hazard ratio [HR] 0.13 [95% confidence interval, CI, 0.06\u20130.26]), 5.8\/1.9 (lenvatinib only: HR 0.28 [95% CI 0.16\u20130.48]), and 7.6\/1.9 (both: HR 0.27 [95% CI 0.13\u20130.54]). The ORR with cabozantinib\/placebo was 21%\/0% (sorafenib only), 4%\/0% (lenvatinib only), and 8%\/0% (both). Disease histology consisted of 150 papillary and 113 follicular, including 43 oncocytic and 36 poorly differentiated. The median PFS (months) with cabozantinib\/placebo was 9.2\/1.9 (papillary: HR 0.27 [95% CI 0.17\u20130.43]), 11.2\/2.5 (follicular: HR 0.18 [95% CI 0.10\u20130.31]), 11.2\/2.5 (oncocytic: HR 0.06 [95% CI 0.02\u20130.21]), and 7.4\/1.8 (poorly differentiated: HR 0.18 [95% CI 0.08\u20130.43]). The ORR with cabozantinib\/placebo was 15%\/0% (papillary), 8%\/0% (follicular), 11%\/0% (oncocytic), and 9%\/0% (poorly differentiated). Safety outcomes evaluated were consistent with those previously observed for the overall population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Results indicate that cabozantinib benefits patients with RAIR DTC, regardless of prior lenvatinib or sorafenib treatments or histology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration Number:<\/jats:title>\n                    <jats:p>NCT03690388.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2023.0463","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T02:41:37Z","timestamp":1702003297000},"page":"347-359","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Increased Progression-Free Survival with Cabozantinib Versus Placebo in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Irrespective of Prior Vascular Endothelial Growth Factor Receptor-Targeted Therapy and Tumor Histology: A Subgroup Analysis of the COSMIC-311 Study"],"prefix":"10.1177","volume":"34","author":[{"given":"Jaume","family":"Capdevila","sequence":"first","affiliation":[{"name":"Gastrointestinal and Endocrine Tumor Unit, Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), IOB Quiron-Teknon, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Krajewska","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Endocrine Oncology, Maria Sk\u0142odowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Hernando","sequence":"additional","affiliation":[{"name":"Vall d'Hebron University Hospital, Vall d\u00b4Hebron Institute of Oncology (VHIO), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven I.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Jarzab","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Endocrine Oncology, Maria Sk\u0142odowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Chi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Vaisman","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Instituto Nacional de C\u00e2ncer, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana O.","family":"Hoff","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Hitre","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Multidisciplinary Head and Neck Cancer Center, Orsz\u00e1gos Onkol\u00f3giai Int\u00e9zet, Budapest, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Bowles","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Exelixis, Inc., Alameda, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Levytskyy","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Exelixis, Inc., Alameda, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Oliver","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, Exelixis, Inc., Alameda, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhumsuk","family":"Keam","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia S.","family":"Brose","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,12,7]]},"reference":[{"key":"e_1_3_6_2_2","unstructured":"National Cancer Institute. 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Cabometyx (cabozantinib) package insert. 2023. Available from: https:\/\/www.cabometyx.com\/downloads\/CABOMETYXUSPI.pdf [Last Accessed: October11 2023]."},{"key":"e_1_3_6_16_2","unstructured":"Exelixis Inc. Cabometyx (cabozantinib) summary of product characterisitcs. 2021. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/cabometyx-epar-product-information_en.pdf [Last Accessed: July27 2022]."},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-020-01362-6"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3588"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10030384"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30166-8"},{"key":"e_1_3_6_21_2","unstructured":"Eisai Inc. Lenvima (lenvatinib) package insert. 2022. 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