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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\u003EData from a Phase 3 study indicate that the use of bevacizumab (BEV) in glioblastoma should not be extended to the first-line setting. Currently, BEV is approved by the United States Food and Drug Administration for the treatment of recurrent glioblastoma. This article discusses findings from the double-blind, placebo-controlled, randomized trial entitled Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma [RTOG 0825; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00884741\u0026amp;atom=%2Fspmdc%2F13%2F6%2F10.atom\u0022\u003ENCT00884741\u003C\/a\u003E; Gilbert MR et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2013 (suppl; abstr 1)].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHead \u0026amp; Neck Cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHead \u0026amp; Neck Cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EData from a Phase 3 study indicate that the use of bevacizumab (BEV) in glioblastoma should not be extended to the first-line setting. Currently, BEV is approved by the United States Food and Drug Administration for the treatment of recurrent glioblastoma.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EFindings from the double-blind, placebo-controlled, randomized trial entitled Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma [RTOG 0825; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00884741\u0026amp;atom=%2Fspmdc%2F13%2F6%2F10.atom\u0022\u003ENCT00884741\u003C\/a\u003E; Gilbert MR et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2013 (suppl; abstr 1)] were announced by Mark R. Gilbert, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, USA, on behalf of the participating cooperative groups: RTOG, NCCTG and ECOG.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe current standard of care for glioblastoma is surgical resection followed by chemoradiation with temozolomide (TMZ), but despite this treatment average survival remains \u0026lt;18 months. Angiogenesis is a hallmark feature of glioblastoma, and vascular endothelial growth factor (VEGF)-A is the most common angiogenic factor produced by glioblastoma tumors. Dr. Gilbert and colleagues therefore explored the utility of BEV, a humanized monoclonal antibody against VEGF-A with demonstrated activity in recurrent glioblastoma, as first-line therapy.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EIn the trial, 637 neurologically stable adults with newly diagnosed glioblastoma underwent 3 weeks of standard chemoradiation with daily TMZ. Patients were then randomized to complete chemoradiation with TMZ with either either placebo or BEV (10 mg\/kg IV Q2W). Patients then continued with maintenance TMZ (Days 1 to 5 of a 28-day cycle) with either placebo or BEV Q2W through 6 to 12 cycles. All patients had undergone surgical resection before starting chemoradiation; \u223c60% in each arm had gross total resection. Nearly 80% of patients received intensity-modulated radiation therapy. At disease progression, the study treatment arm designation could be revealed, at which time patients were allowed to cross over or continue BEV. In the placebo arm, 40.7% of patients crossed over to BEV; 20.9% of patients in the BEV arm stayed on BEV after progression (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). The coprimary endpoints were overall survival (OS) and progression-free survival (PFS).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EAdverse events that were more common with BEV compared with placebo included hypertension (4.6% vs 1.0%), deep vein thrombosis\/pulmonary embolism (9.9% vs 7.7%), wound healing issues (2.3.% vs 1.0%), gastrointestinal perforation (1.3% vs 0.7%), significant hemorrhage (1.3% vs 1.0%), and neutropenia (15.1% vs 7.3%).\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003ESome 40.7% of pateints in the placebo arm crossed over to BEV; 20.9% of patients in the BEV arm sayted on BEV after progression (\u003Ca id=\u0022xref-table-wrap-1-2\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/13437\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/13437\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13437\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EChemotherapy Received at Progression\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003EThe median OS was 16.1 months in those randomized to placebo versus 15.7 months with randomization to BEV (HR, 1.13; p=0.21). The median PFS was longer by 3.4 months in the BEV group relative to the placebo group (10.7 vs 7.3 months; HR, 0.79; p=0.007), but this difference did not reach the prespecified 30% reduction in hazard of failure with a p value of 0.004 prescribed for the study. Methylation status of the \u003Cem\u003EO-6 Methylguanine-DNA Methyltransferase (MGMT)\u003C\/em\u003E gene promoter was prognostic, with unmethylated status demonstrating significantly worse median OS and PFS. A subgroup analysis based on \u003Cem\u003EMGMT\u003C\/em\u003E methylation status, a 9-gene expression signature, and Clinical Prognostic Groups found no differences in outcomes between treatments by subgroup (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/13439\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/13439\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13439\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003EOutcomes by Subgroup\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-12\u0022\u003EA prespecified analysis evaluated symptom burden, health-related quality of life and neurocognitive function in patients who were deemed to be progression-free. This study showed that patients on the BEV arm had a greater increase of patient-reported symptom burden and more decline of neurocognitive function and quality of life over time compared with patients in the placebo arm.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EPreliminary molecular analysis from a subset of tumor tissues suggests that a molecular profile may be able to identify a subgroup of patients that could benefit from BEV in the first-line setting. However, until a patient subgroup can be identified, the results of the study do not support the use of BEV in the first-line setting for glioblastoma.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\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\/13\/6\/10.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?nznv81\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nznv81\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}