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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\u003ELUX-Lung 5 is the first prospective randomized, phase 3 trial to demonstrate superior progression-free survival by continuing afatinib plus paclitaxel as fourth-line treatment vs single-agent chemotherapy in patients with non\u2013small cell lung cancer who had disease progression on chemotherapy with the combination of erlotinib plus gefitinib and with afatinib monotherapy with a manageable safety profile.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Emetastatic non\u2013small cell lung cancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELUX-Lung 5\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eafatinib\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eerlotinib\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Egefitinib\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Epaclitaxel\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Efourth-line treatment\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eprogression-free survival\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eoverall survival\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Edisease control rate\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eoverall response\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eoncology clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EPatients with advanced non\u2013small cell lung cancer (NSCLC) who have wild-type \u003Cem\u003EEGFR\u003C\/em\u003E fare better with conventional chemotherapy instead of tyrosine kinase inhibitors (TKIs) as first-line treatment [Lee JK et al. \u003Cem\u003EJAMA\u003C\/em\u003E. 2014]. In contrast, 70% of patients with NSCLC harboring \u003Cem\u003EEGFR\u003C\/em\u003E mutations show tumor regression from the EGFR TKIs erlotinib and gefitinib [Jackman D et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2010]. The majority of these patients eventually acquire resistance to erlotinib and gefitinib, contributing to disease progression.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EBecause of tumor cell heterogeneity, inclusion of an EGFR TKI in postprogression therapy improves outcomes. For instance, a combination of gefitinib or erlotinib plus pemetrexed has been shown to improve outcomes in 27 patients with EGFR mutation-positive NSCLC who had disease progression on gefitinib\/erlotinib monotherapy; an overall response rate of 25.9% (95% CI, 62.1% to 95.5%) was achieved with the combination [Yoshimura N et al. \u003Cem\u003EJ Thorac Oncol\u003C\/em\u003E. 2013]. Afatinib, an irreversible ErbB TKI (including EGFR, HER2, HER4), increases survival outcomes as monotherapy and overcomes resistance in patients who had disease progression after gefitinib\/erlotinib [Katakami N et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2013; Sequist LV et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2013].\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EMartin Schuler, MD, West German Cancer Center, Essen, Germany, shared results of LUX-Lung 5 [Schuler M et al. \u003Cem\u003EAnn Oncol.\u003C\/em\u003E 2015], a randomized, open-label, 2-stage design, phase 3 trial that assessed continued afatinib plus paclitaxel vs investigator\u2019s choice of single-agent chemotherapy (ICC). The study consisted of 2 parts. In part A, patients with NSCLC who had failed \u2265\u20051 line of chemotherapy (including platinum\/pemetrexed) and erlotinib\/gefitinib after \u2265\u200512 weeks of treatment (n\u2005=\u20051154) were treated with afatinib 50 mg\/d. In part B, patients who had been treated with afatinib for \u2265\u200512 weeks followed by disease progression after part A of the study were eligible to be randomized 2:1 to afatinib 40 mg\/d plus paclitaxel 80 mg\/m\u003Csup\u003E2\u003C\/sup\u003E\/wk or ICC. The primary end point was progression-free survival, whereas the secondary end points included overall survival, objective response rate, safety, and health-related quality-of-life outcomes.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EOf the 1154 patients who had disease progression on erlotinib\/gefitinib and afatinib 50 mg\/d, 202 patients derived \u2265\u200512 weeks of benefit on afatinib monotherapy. These selected patients were randomized 2:1 to receive afatinib plus paclitaxel (n\u2005=\u2005134; 40 mg\/d; 80 mg\/m\u003Csup\u003E2\u003C\/sup\u003E\/wk) or ICC (n\u2005=\u200568). Baseline patient characteristics (included sex, age, ECOG performance status, race, smoking status, clinical stage, and tumor histology) were well balanced between both arms. Progression-free survival increased from 2.8 months with ICC to 5.6 months with afatinib plus paclitaxel (HR, 0.60; 95% CI, 0.43 to 0.85; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.0031). Afatinib plus paclitaxel, as fourth-line treatment, was also more effective than ICC in reducing tumor size (15.1% vs 1.2%).\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EAlthough disease control rate (OR, 3.4; \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.0001) and objective response rate (OR, 3.1; \u003Cem\u003EP\u2005\u003C\/em\u003E=\u2005.0049) were superior with afatinib plus paclitaxel, overall survival did not show any statistical difference between the 2 treatment arms (12.2 months in each arm; HR, 1.00; 95% CI, 0.70 to 1.43; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.994), possibly attributed to differences in postprogression treatment between the arms. More patients in the ICC arm received 2 postprogression lines of therapy compared with the afatinib plus paclitaxel arm (36% vs 15%).\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EDespite prolonged exposure time to afatinib plus paclitaxel compared with ICC (133 vs 51 days), discontinuation due to treatment-related adverse events was low, and quality of life was comparable between arms (HR, 0.97; 95% CI, 0.6 to 1.5). The most common adverse events in afatinib plus paclitaxel vs ICC arms included diarrhea (53.8% vs 6.7%), alopecia (32.6% vs 15%), and asthenia (27.3% vs 28.3%).\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EProf Schuler concluded that afatinib plus paclitaxel was superior to ICC and improved outcomes in patients who had an acquired resistance to erlotinib\/gefitinib and had disease progression on afatinib monotherapy after an initial benefit. It should, however, be noted that this study did not include a mutational analysis. Future studies should include a mutational status analysis (including \u003Cem\u003EEGFR\u003C\/em\u003E mutations) to evaluate how the efficacy of treatments differs based on mutational status.\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\/8\/13.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?nzl1bq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}