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{\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/36\\\/18-b\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/36\\\/18-b\u0022}],\u0022ac\u0022:{\u0022spmdc;14\\\/36\\\/18-b\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;14\\\/36\\\/18-b\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.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\u003EAs second-line therapy for hepatocellular carcinoma, ramucirumab did not improve overall survival compared with placebo in a phase 3 randomized study, but benefit was observed in a selected population with an elevated baseline level of alpha-fetoprotein. The results of the randomized, phase 3 Ramucirumab Second-Line Treatment in Patients With Hepatocellular Carcinoma After First-Line Therapy With Sorafenib study [REACH; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01140347\u0026amp;atom=%2Fspmdc%2F14%2F36%2F18.2.atom\u0022\u003ENCT01140347\u003C\/a\u003E] are discussed in this article.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECancers of the Accessory Digestive Organs\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EGastrointestinal Cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECancers of the Accessory Digestive Organs\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EGastrointestinal Cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EAs second-line therapy for hepatocellular carcinoma (HCC), ramucirumab (RAM) did not improve overall survival (OS) compared with placebo (PBO) in a phase 3 randomized study, but benefit was observed in a selected population with an elevated baseline level of alpha-fetoprotein (AFP). The results of the randomized, phase 3 Ramucirumab Second-Line Treatment in Patients With Hepatocellular Carcinoma After First-Line Therapy With Sorafenib study [REACH; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01140347\u0026amp;atom=%2Fspmdc%2F14%2F36%2F18.2.atom\u0022\u003ENCT01140347\u003C\/a\u003E] were presented by Andrew X. Zhu, MD, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ECurrently, no treatment has demonstrated a survival benefit in a second-line setting (after sorafenib) in HCC [Zhu AX et al. \u003Cem\u003EJAMA\u003C\/em\u003E. 2014; Llovet JM et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2013]. Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2)-mediated signaling and angiogenesis are likely contributors to HCC tumor growth. RAM is a human immunoglobulin G1 monoclonal antibody that binds to the extracellular domain of VEGFR-2, preventing ligand binding and receptor activation. Preliminary evidence of RAM\u0027s anticancer activity was demonstrated in patients with treatment-na\u00efve HCC in a single-arm phase 2 study [Zhu AX et al. \u003Cem\u003EClin Cancer Res.\u003C\/em\u003E 2013].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EREACH evaluated the safety and efficacy of RAM in 565 patients with advanced HCC following first-line therapy with sorafenib. The primary end point was OS with progression-free survival (PFS), objective response rate (ORR), and safety included as secondary end points. Eligible patients had advanced HCC confirmed by histology or radiographic imaging to be Barcelona Clinic Liver Cancer stage C or B, were refractory or not amenable to locoregional therapy, were Child-Pugh Class A, and had disease progression during or following sorafenib therapy (or were intolerant to sorafenib). Patients were randomized to RAM 8 mg\/kg intravenously (n = 283) plus best supportive care (BSC), or PBO (n = 282) plus BSC every 2 weeks per cycle, until disease progression or unacceptable toxicity. Baseline demographics and characteristics were balanced between the 2 arms.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe safety population consisted of 553 patients (277 in the RAM arm and 276 in the PBO arm). Grade \u2265 3 treatment-related adverse events reported in \u2265 3% of patients in the RAM arm included hypertension (12% in the RAM arm vs 4% in the PBO arm), thrombocytopenia (5% vs \u0026lt; 1%), hepatic encephalopathy (3% vs \u0026lt; 1%), and neutropenia (3% vs 1%). Bleeding or hemorrhage of any grade occurred in 33% of the RAM group and 20% of the PBO group; liver injury or failure in 51% and 37%, respectively; and proteinuria in 17% and 5%, respectively (\u003Ca id=\u0022xref-table-wrap-1-1\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\/12099\/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\/12099\/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\/12099\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-6\u0022 class=\u0022first-child\u0022\u003EAdverse Events of Special Interest in REACH\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EIn the intention-to-treat population, median OS was 9.2 months in the RAM arm and 7.6 months in the PBO arm (HR, 0.866; \u003Cem\u003EP\u003C\/em\u003E = .1391). Median PFS was 2.8 months in the RAM arm and 2.1 months in the PBO arm (HR, 0.625; \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .0001). The median time to progression was 3.5 months in the RAM arm vs 2.6 months in the PBO arm (\u003Cem\u003EP\u003C\/em\u003E \u0026lt; .0001). The 6-month PFS rates were 37.0% in RAM recipients and 14.9% in PBO recipients, and the 9-month PFS rates were 27.0% and 10.8%, respectively. The objective response rates were 7.1% in the RAM arm and 0.7% in the PBO arm (\u003Cem\u003EP\u003C\/em\u003E \u0026lt; .0001), and the disease control rates were 56.2% and 45.7% (\u003Cem\u003EP\u003C\/em\u003E = .0110), respectively (\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\/12100\/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\/12100\/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\/12100\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-12\u0022 class=\u0022first-child\u0022\u003ETumor Response Rates in REACH\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-15\u0022\u003ETwo hundred and fifty patients had a baseline AFP level \u2265 400 ng\/mL. In a prespecified analysis of OS in this subgroup, the OS HR in the RAM group compared with PBO was 0.674 (\u003Cem\u003EP\u003C\/em\u003E = .0059), with a median OS of 7.8 months in the RAM group vs 4.2 months in the PBO group.\u003C\/p\u003E\u003Cp id=\u0022p-16\u0022\u003EDr Zhu concluded that although REACH did not demonstrate a significant improvement in OS with RAM in the intent-to-treat population, an elevated baseline AFP may select a population likely to benefit. Further investigation of RAM is warranted based on the REACH results and the unmet need in this disease.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 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\/14\/36\/18.2.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?nzm0a2\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?nzm0a2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}