{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:25:53Z","timestamp":1756189553709,"version":"3.40.4"},"reference-count":41,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T00:00:00Z","timestamp":1719619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Millennium Pharmaceuticals, Inc. (Cambridge"},{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company, Limited","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017658","name":"Calithera Biosciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017658","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>There are limited therapeutic options for patients with recurrent\/metastatic anaplastic thyroid carcinoma (ATC) and radioiodine refractory (RAIR) differentiated thyroid carcinoma (DTC) refractory to multikinase inhibitors. This multicenter trial evaluated sapanisertib, a next-generation oral kinase inhibitor of mTOR complexes 1\/2, in ATC and RAIR DTC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A safety run-in phase I was followed by nonrandomized phase II trial in ATC, with an exploratory cohort in RAIR DTC. The primary endpoint was the proportion of patients with ATC who were without disease progression at 4 months. Safety and survival outcomes were key secondary endpoints.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Forty-six patients (20 ATC, 26 DTC) were enrolled including 40 (18 ATC, 22 DTC) who received recommended phase II dose of 5 mg daily. Eleven percent [2\/18, 95% confidence interval (CI): 1.4-34.7%] of patients with ATC were progression-free at 4 months; 22.2% (4\/18) had stable disease as best response. Enrollment in the ATC cohort stopped early with 18 patients out of the proposed 23 due to overall futility. One confirmed partial response (4.5%, 1\/22) occurred in RAIR DTC, with stable disease in 63.6% (14\/22) patients. Median progression-free survival was 1.6 (95% CI: 0.9-2.8) months and 7.8 (2.0\u2013not reached) months in ATC and DTC, respectively. Grade 3 treatment-related adverse events occurred in 30% of patients who received the phase II dose, with the most common being anorexia, nausea, diarrhea, fatigue, skin rash, and hyperglycemia. Genomic alterations in the PI3K\/AKT\/mTOR pathway were not associated with response or progression-free survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Sapanisertib monotherapy did not meet the primary endpoint of this trial (proportion progression-free at 4 months) in ATC and did not show clinically meaningful activity. Clinical trials with alternative therapeutic strategies are needed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae443","type":"journal-article","created":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T17:17:50Z","timestamp":1719681470000},"page":"1315-1323","source":"Crossref","is-referenced-by-count":6,"title":["A Phase I\/II Trial of Sapanisertib in Advanced Anaplastic and Radioiodine Refractory Differentiated Thyroid Carcinoma"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4391-6943","authenticated-orcid":false,"given":"Kartik","family":"Sehgal","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Division of Head and Neck Oncology, Dana-Farber Cancer Institute , Boston, MA 02215 ,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Medicine, Brigham and Women's Hospital , Boston, MA 02115 ,","place":["USA"]},{"name":"Thyroid Cancer Center, Dana-Farber Cancer Institute , Boston, MA 02215 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Serritella","sequence":"additional","affiliation":[{"name":"Head and Neck\/Thyroid Program, Robert H. 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