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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\u003EThe randomized Phase 3 Cetuximab Combined With Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer trial [CRYSTAL; Van Cutsem E et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009] investigated the efficacy and safety of cetuximab combined with a simplified regimen of leucovorin\u20135-flourouracil\u2014irinotecan (FOLFIRI) for the initial treatment of metastatic colorectal cancer.\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\u003EGastrointestinal Cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\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\u003EThe randomized Phase 3 Cetuximab Combined With Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer trial [CRYSTAL; Van Cutsem E et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009] investigated the efficacy and safety of cetuximab combined with a simplified regimen of leucovorin\u20135-flourouracil\u2014irinotecan (FOLFIRI) for the initial treatment of metastatic colorectal cancer. The study found that cetuximab (CET) added to FOLFIRI improved progression-free survival (PFS), overall survival (OS), and response in patients with \u003Cem\u003EKRAS\u003C\/em\u003E 12\/13 (exon 2) wild-type disease [Van Cutsem E et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009; Van Cutsem E et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2011]. Patients with \u003Cem\u003EKRAS\u003C\/em\u003E exon 2 mutations did not benefit from treatment.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe aim of this analysis of the CRYSTAL study [\u003Cem\u003EAnn Oncol\u003C\/em\u003E 2014 (abstr O-0020); Ciardello F et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2014 (abstr 3506)], presented by Eric Van Cutsem, MD, Department of Clinical Digestive Oncology, Leuven Cancer Institute, UZ Leuven, Leuven, Belgium, was to assess the efficacy of CET added to FOLFIRI in patients who had metastatic colorectal cancer with new \u003Cem\u003ERAS\u003C\/em\u003E mutations.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003E\n         \u003Cem\u003EKRAS\u003C\/em\u003E exon 2 wild-type tumor samples from CRYSTAL study patients were screened for 26 new \u003Cem\u003ERAS\u003C\/em\u003E mutations in 4 additional \u003Cem\u003EKRAS\u003C\/em\u003E codons (exons 3 and 4) and 6 \u003Cem\u003ENRAS\u003C\/em\u003E codons (exons 2, 3, and 4) using a technique based on polymerase chain reaction (PCR) amplification of single target DNA molecules. Flow cytometry and fluorescent probes were used to identify wild-type and mutant sequences. The ratio of mutant to wild-type \u003Cem\u003ERAS\u003C\/em\u003E DNA molecules in the original tumor DNA sample was determined for patients in whom mutations were identified. A 5% cutoff was selected for the analysis. Treatment outcomes were evaluated according to whether the patients had \u003Cem\u003ERAS\u003C\/em\u003E wild-type, new \u003Cem\u003ERAS\u003C\/em\u003E mutations, or \u003Cem\u003ERAS\u003C\/em\u003E mutations (\u003Cem\u003EKRAS\u003C\/em\u003E exon 2 or new \u003Cem\u003ERAS\u003C\/em\u003E).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EMutation status was evaluated in 430 of 666 patients (65%) with \u003Cem\u003EKRAS\u003C\/em\u003E exon 2 wild-type tumors. Using the 5% cutoff, new \u003Cem\u003ERAS\u003C\/em\u003E mutations were identified in 63 of the 430 patients (15%). Comparison of outcomes with mutation status showed that patients with \u003Cem\u003ERAS\u003C\/em\u003E wild-type (all loci) tumors treated with CET plus FOLFIRI versus FOLFIRI alone had significantly better response rates (66.3% vs 38.6%; odds ratio, 3.11; 95% CI, 2.03 to 4.78; p \u0026lt; .0001), median PFS (11.4 vs 8.4 months; HR, 0.56; 95% CI, 0.41 to 0.76; p = .0002), and median OS (28.4 vs 20.2 months; HR, 0.69; 95% CI, 0.54 to 0.88; p = .0024). The subgroup with new \u003Cem\u003ERAS\u003C\/em\u003E mutations and those with \u003Cem\u003ERAS\u003C\/em\u003E mutations at any locus derived no benefit from the addition of CET to FOLFIRI with respect to response rate, PFS, and OS (\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\/14869\/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\/14869\/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\/14869\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\u003ECRYSTAL Trial Outcomes of Cetuximab Added to FOLFIRI\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\u003EAnalysis of treatment outcomes in subgroups with new \u003Cem\u003ERAS\u003C\/em\u003E mutations defined according to a range of sensitivity cutoffs from 20% to .1% supported the use of 5% as a clinically appropriate cutoff point for defining a subgroup of patients most likely to benefit from the addition of CET to FOLFIRI.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EDr. Van Cutsem concluded that in the first-line treatment of metastatic colorectal cancer, patients with \u003Cem\u003ERAS\u003C\/em\u003E wild-type tumors derived a marked benefit throughout all efficacy end points with the addition of CET to FOLFIRI. Patients with \u003Cem\u003ERAS\u003C\/em\u003E tumor mutations did not benefit from treatment with CET. These results support patient selection according to \u003Cem\u003ERAS\u003C\/em\u003E mutation status to maximize benefit from CET therapy.\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\/22\/9.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?nzoxlp\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?nzoxlp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}