{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\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_at_symbol.js?nzpb9d\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_article_reference_popup.js?nzpb9d\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\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\\\/3\\\/29\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/3\\\/29\u0022}],\u0022ac\u0022:{\u0022spmdc;14\\\/3\\\/29\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;14\\\/3\\\/29\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\/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\u003EImmunotherapy for the treatment of non\u2014small cell lung cancer (NSCLC) is being actively investigated, with promising results being reported. This article provides an overview of the immune system in lung cancer, while discussing emerging therapies that target immune checkpoints and combination immunotherapies.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERespiratory Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECancer Genomics\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERespiratory Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EImmunotherapy for the treatment of non-small cell lung cancer (NSCLC) is being actively investigated, with promising results being reported. David P. Carbone, MD, PhD, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA, provided an overview of the immune system in lung cancer.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe immune system uses multiple methods to target foreign bodies, including natural killer cells, granulocytes, and macrophages; antibody-dependent cellular immunity; and cellular immunity. Cellular immunity detects neoantigens presented on class I major histocompatibility complex (MHC) and can specifically recognize oncoproteins with somatic mutations. Peptides derived from proteins degraded by proteasomes are then processed by the Golgi complex and transported to the cell surface bound to a MHC I, where the peptides are presented to cytotoxic T cells. This process is modulated by multiple costimulatory and inhibitory interactions mediated by various receptor-ligand pairs [Pardoll DM. \u003Cem\u003ENat Rev Cancer\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EMutations in genes that code for MHC I, TAP, and beta-2 microglobulin have been identified and can result in an inability of the cell to present antigens via MHC I. Although there is surveillance for tumor cells by the immune system, up to 10% of tumors are believed to have mutations that affect MHC I presentation, and 90% to 95% of tumors demonstrate a failure to induce an immune response or failure of T cells to kill the afflicted cell.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003ERoy S. Herbst, MD, PhD, Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven, Connecticut, USA, discussed emerging therapies that target immune checkpoints. Two recently popular targets are programmed death 1 (PD-1) and PD ligand 1 (PD-L1), which play a role in reducing the anti-tumor response.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ETheanti-PD-1 agent nivolumab was evaluated in a Phase 1 trial in 129 patients with refractory NSCLC. At the 3 mg\/kg dose, the result was a median overall survival (OS) of 14.9 months [Brahmer JR et al. ASCO 2013. Abstract 8030], the 1-year OS rate was 42%, and the 2-year OS rate was 24%. Adverse events affecting the skin and the gastrointestinal, pulmonary, endocrine, and hepatic systems occurred, with 8 patients developing drug-related pneumonitis that resulted in 2 deaths. Recently, two Phase 3 trials of nivolumab were completed, although results have not yet been reported.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EAnother anti-PD-1 antibody is MK-3475, which was evaluated in patients previously treated for NSCLC [Unpublished]. Dr. Herbst pointed out that the outcome of this trial is similar to what was observed in the trial that evaluated nivolumab. The overall response rate was 24%, and the median OS was 51 weeks. A Phase 3 trial is currently recruiting patients who will be randomly assigned to receive two different doses of MK-3475 or docetaxel.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EAn antibody targeting PD-L1, MPDL3280A, demonstrated a 23% overall response rate in a Phase 1 trial, with some patients responding early in treatment and others later [Gettinger SN et al. WCLC 2013; Spigel DR et al. ASCO 2013. Abstract 8008]. The vaccine was generally well tolerated, with no dose-limiting toxicities. Interestingly, a response was observed in patients who were smokers and in those with EGFR or KRAS mutations [Gettinger SN et al. WCLC 2013]. Frequent adverse events included fatigue (20%), nausea (14%), decreased appetite (12%), and dyspnea (9%) [Gettinger SN et al. WCLC 2013].\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EAnother anti-PD-L1 vaccine is MEDI4736, which was evaluated in a Phase 1 study and demonstrated a response resulting in stable disease or partial response in some patients [Khleif SN et al. ESMO 2013. Abstract 802]. The vaccine was well tolerated with no grade 3 or 4 adverse events or deaths reported. Common adverse events included diarrhea (18%), vomiting (18%), and dizziness (18%).\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EMartin Reck, MD, PhD, Lungen Clinic Grosshansdorf, Germany, discussed combination immunotherapies. Some reasons for combining immunotherapy with systemic treatment are that cell death can generate tumor antigens, alterations in tumor architecture can increase the penetration of immunotherapy, and combination with immunotherapy may help the systemic therapy to overcome resistance. The combination of immunotherapy with systemic therapy began in the treatment of melanoma with the blockade of CTLA-4 by ipilimumab, and it has now moved into experimental lung cancer treatments.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EA Phase 2 study evaluated ipilimumab plus paclitaxel and carboplatin in NSCLC and metastatic SCLC [Lynch TJ et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2012]. According to RECIST criteria, progression-free survival (PFS) was improved in the phased schedule, but not in the concurrent schedule. According to histologic type, patients with squamous cell lung cancer appeared to benefit the most from phased combination therapy [Lynch TJ. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2012]. The sequential schedule of ipilimumab plus chemotherapy is currently being further evaluated in Phase 3 trials.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003ECombination therapy with nivolumab and chemotherapy is currently being evaluated in a Phase 1 study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01454102\u0026amp;atom=%2Fspmdc%2F14%2F3%2F29.atom\u0022\u003ENCT01454102\u003C\/a\u003E]. Patients will be assigned to 1 of 13 treatment arms: (A) cisplatin plus gemcitabine and nivolumab, (B) cisplatin plus pemetrexed and nivolumab, (C) carboplatin plus paclitaxel and nivolumab, (D) maintenance therapy with bevacizumab plus nivolumab, (E) eribulin plus nivolumab in patients with EGFR mutations, (F) nivolumab monotherapy, (G-J) ipilimumab plus nivolumab, (K) maintenance therapy with nivolumab monotherapy after platinum-doublet chemotherapy without progressive disease, (L) maintenance therapy with nivolumab after platinum-doublet chemotherapy with or without bevacizumab without progressive disease, and (M) nivolumab monotherapy in patients with untreated, asymptomatic brain metastases. The first reported efficacy data were reported for arms A through C [Rizvi NA et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2013. Abstract 8072]. The overall tumor response rate was 33%, 47%, 47%, and 50%, for arms A, B, C at 10 mg\/kg nivolumab, and C at 5 mg\/kg nivolumab, respectively.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EImmunotherapy for the treatment of NSCLC has demonstrated promising results across different methodologies, including targeted antibodies and cancer vaccines. Many agents are currently being evaluated in Phase 2 or 3 clinical trials, with their results much anticipated.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/3\/29\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022The editors would like to thank the many members of the 2014 European Lung Cancer Conference presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1418488918\u0022 data-figure-caption=\u0022The editors would like to thank the many members of the 2014 European Lung Cancer Conference presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure1\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/3\/29\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/3\/29\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure1\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/3\/29\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15821\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\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\n            \u003Cp id=\u0022p-14\u0022 class=\u0022first-child\u0022\u003EThe editors would like to thank the many members of the 2014 European Lung Cancer Conference presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\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\/3\/29.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_figures.js?nzpb9d\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_openurl.js?nzpb9d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}