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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\u003EPatients that received customized lung cancer treatment based on their levels of BRCA1 and RAP80 did not experience an improvement in progression-free survival or overall survival (OS), compared with standard cisplatin plus docetaxel. This article presents data from the Multicenter, Predictive, Prospective, Phase 3, Open, Randomized Pharmacogenomic Study in Patients With Advanced Lung Carcinoma study [BREC; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00617656\u0026amp;atom=%2Fspmdc%2F13%2F6%2F22.2.atom\u0022\u003ENCT00617656\u003C\/a\u003E; Moran T et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2013 (suppl; abstr LBA8002)].\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\u003ECancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERespiratory 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\u003ECancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERespiratory Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EPatients that received customized lung cancer treatment based on their levels of BRCA1 and RAP80 did not experience an improvement in progression-free survival (PFS) or overall survival (OS), compared with standard cisplatin (CIS) plus docetaxel (DOC). Rafael Rosell, MD, USP Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Barcelona, Spain, presented data from the Multicenter, Predictive, Prospective, Phase 3, Open, Randomized Pharmacogenomic Study in Patients With Advanced Lung Carcinoma study [BREC; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00617656\u0026amp;atom=%2Fspmdc%2F13%2F6%2F22.2.atom\u0022\u003ENCT00617656\u003C\/a\u003E; Moran T et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2013 (suppl; abstr LBA8002)].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EPrevious studies have demonstrated that levels of BRCA1 and a component of the BRCA1 complex, called RAP80, can influence patient outcomes when treated with CIS plus gemcitabine (GEM), CIS plus DOC, or DOC alone [Rosell R et al. \u003Cem\u003EPLoS ONE\u003C\/em\u003E 2009]. Overexpression of BRCA1 can confer resistance to agents such as CIS, yet high sensitivity to agents such as paclitaxel, DOC, and vinorelbine [Quinn JE et al. \u003Cem\u003ECancer Res\u003C\/em\u003E 2003]. The hypothesis of the BREC trial was that customizing lung cancer treatment based on BRCA1 and RAP80 levels would improve patient outcomes compared with noncustomized CIS plus DOC.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn the multicenter, prospective Phase 3 BREC trial, 382 patients with advanced lung cancer and wild-type EGFR were randomized 1:1 to receive treatment based on BRCA1 or RAP80 levels or standard treatment with CIS and DOC. Patients with low levels of RAP80 received CIS and GEM, regardless of BRCA1 levels; patients with intermediate to high levels of RAP80 and low to intermediate levels of BRCA1 received CIS and DOC; and patients with intermediate to high levels of RAP80 and high BRCA1 levels received DOC only.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe histology of the tumors was 50.9% adenocarcinoma, 35.5% squamous-cell carcinoma, 8.2% large-cell carcinoma, and 5.4% undifferentiated carcinoma. The primary endpoint of the BREC study was PFS. OS and tumor response rate, as measured by RECIST, were the secondary endpoints of the trial. The planned interim analysis occurred when disease progression occurred in 50% of the patients. The interim analysis analyzed data from 287 patients.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe primary endpoint was not reached. PFS was significantly longer in the control arm, with a PFS of 5.49 months, compared with 4.38 months in the experimental arm (p=0.07), resulting in an HR of 1.35 (95% CI, 1.02 to 1.78; p=0.03). Interestingly, the PFS was similar among the patients that received DOC plus CIS (control arm; 5.49 months), GEM plus CIS (5.43 months), and DOC plus CIS (5.49 months). However, patients that received only DOC had a median PFS of 2.50 months (p=0.003) associated with an HR of 2.65 (p=0.0001). In addition, the rate of OS was 12.66 months in the control arm, compared with 8.52 months in the experimental arm (p=0.006). Patients that received GEM plus CIS, DOC plus CIS, and DOC alone had an OS of 7.70 months (p=0.02), 11.25 months (p=0.28), and 7.24 months (p=0.001), respectively.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EA multivariate analysis of the experimental arm, BRCA1, RAP80, tumor histology, smoking status, and metastatic site was performed. An increased risk of progression was associated only with extrathoracic metastases (HR, 1.78; p=0.02).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EDue to the increased risk of PFS in the experimental group, the BREC trial was closed prematurely. Prof. Rosell concluded by suggesting that the negative outcome of the study may have been, in part, due to the poor predictive capacity of RAP80 for treatment customization. In addition, he pointed out that DOC plus CIS may not be an optimal choice for the control arm.\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\/22.2.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?nznwc2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}