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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EIn the SELECT trial, lenvatinib treatment of patients with radioactive iodine 131\u2013refractory differentiated thyroid cancer was associated with increased thyroid-stimulating hormone levels. An exploratory analysis found that worst postbaseline thyroid-stimulating hormone levels were not associated with differences in overall safety, progression-free survival, overall survival, or overall response rate.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Edifferentiated thyroid cancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Erefractory thyroid cancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elenvatinib\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ESELECT\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ethyroid disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EIncreased thyroid-stimulating hormone (TSH) levels due to lenvatinib treatment in patients with radioactive iodine 131 (\u003Csup\u003E131\u003C\/sup\u003EI)-refractory differentiated thyroid cancer (DTC) were not associated with differences in overall safety, efficacy, or lenvatinib exposure, based on measurement of worst postbaseline TSH levels.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003ESteven I. Sherman, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, USA, presented data from an exploratory analysis of the SELECT trial [Schlumberger M et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2015], a randomized phase 3 trial of lenvatinib in \u003Csup\u003E131\u003C\/sup\u003EI-refractory DTC demonstrating significantly improved progression-free survival (PFS) and response rates compared with placebo. The purpose of this exploratory analysis was to evaluate the effect of thyroid abnormalities on the outcomes observed in the SELECT trial.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003ELenvatinib is a tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1 through 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor \u03b1, ret proto-oncogenes, and stem-cell receptors [Okamoto K et al. \u003Cem\u003ECancer Lett.\u003C\/em\u003E 2013; Matsui J et al. \u003Cem\u003EInt J Cancer.\u003C\/em\u003E 2008]. A common side effect of tyrosine kinase inhibitors with multiple targets is hypothyroidism [Rini B et al. \u003Cem\u003EJ Natl Cancer Inst.\u003C\/em\u003E 2007] and exacerbation of postsurgical hypothyroidism [Brose MS et al. \u003Cem\u003ELancet.\u003C\/em\u003E 2014; Elisei R et al. \u003Cem\u003EJ Clin Oncol.\u003C\/em\u003E 2013], which may be associated with response to therapy [Kust D et al. \u003Cem\u003EAnticancer Res.\u003C\/em\u003E 2014; Schmidinger M et al. \u003Cem\u003ECancer\u003C\/em\u003E. 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EIn the double-blind, phase 3 SELECT trial, 392 adult patients with \u003Csup\u003E131\u003C\/sup\u003EI-refractory DTC were randomly assigned 2:1 to receive lenvatinib or placebo until disease progression [Schlumberger M et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2015]. The primary end point was PFS, and the secondary end points were overall response rate, overall survival, and safety. Patients who were assigned to placebo were able to switch to open-label lenvatinib after disease progression. All patients received concomitant thyroid hormone suppression, primarily via levothyroxine.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EIn this exploratory analysis, patients in the lenvatinib arm experienced higher TSH levels by cycle 1 that peaked by cycle 2 and steadily declined after cycle 4. In contrast, patients in the placebo arm did not experience consistent changes in TSH levels. In the lenvatinib arm, 28.4% of patients experienced worst postbaseline TSH levels\u2005\u0026gt;\u20055.5 mIU\/L compared with 6.2% of patients in the placebo arm.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EWorst postbaseline TSH levels were not associated with dose modification of lenvatinib, study drug withdrawal, treatment exposure, or lenvatinib-related adverse events. However, lenvatinib-related thyrotoxicosis and exacerbation of hypothyroidism occurred primarily in patients who had worst postbaseline TSH levels\u2005\u0026gt;\u20055.0 mIU\/L. In addition, QTc prolongation occurred more frequently in patients who had worst postbaseline TSH levels of \u0026gt;\u20055.0 mIU\/L (12.5%) compared with patients who had worst postbaseline TSH levels of \u0026gt;\u20050.5 to 5.0 mIU\/L (6.4%) or \u2264\u20050.5 mIU\/L (4%). PFS, overall survival, and overall response rate were not significantly different among the worst postbaseline TSH level categories.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EDr Sherman indicated that the data from this exploratory analysis of the SELECT trial suggest that there is no association between worst postbaseline TSH levels on overall lenvatinib safety or efficacy, as well as lenvatinib exposure. In addition, although increased TSH levels occurred frequently, it was not known if the rise was a result of lenvatinib or modification of TSH-suppression therapy because of patient intolerance to TSH suppression. Dr Sherman stated that a longitudinal analysis of TSH levels may be warranted and could provide further information than this single\u2013time point analysis.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/4\/15.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzl13d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}