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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\u003EDuring the past 50 years, substantial progress has been made in the treatment of the most common type of lung cancer, non\u2014small cell lung cancer (NSCLC). This article discusses adjuvant therapy in NSCLC, the treatment of locally advanced stage III NSCLC, as well as progress in the treatment of advanced NSCLC.\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\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary Guidelines 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\u003EPulmonary Guidelines\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\u003EDuring the past 50 years, substantial progress has been made in the treatment of the most common type of lung cancer, non\u2013small cell lung cancer (NSCLC).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EHeather Wakelee, MD, Stanford University, Stanford, California, USA, reviewed adjuvant therapy in NSCLC. A meta-analysis of \u0026gt;1300 patients enrolled in 8 clinical trials published in 1995 generated enthusiasm for the use of cisplatin in the adjuvant setting, reporting a 5% survival benefit at 5 years that did not quite achieve significance (p=0.08) [Non\u2013small Cell Lung Cancer Collaborative Group \u003Cem\u003EBMJ\u003C\/em\u003E 1995]. After disappointing outcomes obtained with adjuvant cisplatin-based regimens from multiple randomized Phase 3 trials, the International Adjuvant Lung Cancer Trial [IALT] (n=1867) found a 4% 5-year survival benefit to adjuvant cisplatin (p\u0026lt;0.03) [Arriagada R et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2004]. The long-term follow-up of IALT in 2009 was disappointing in that the HR for overall survival (OS) was no longer significant (p=0.10), but the benefit on disease-free survival persisted (p=0.02) [Arriagada R et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2010]. Later adjuvant chemotherapy trials in which a doublet of cisplatin and vinorelbine was used maintained their survival benefits even with long-term follow-up. One such trial was the Adjuvant Navelbine International Trialist Association [ANITA], which reported an OS HR of 0.80 (p=0.017) [Douillard JY et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2006].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe Lung Adjuvant Cisplatin Evaluation [LACE] meta-analysis included 4584 patients from the 5 largest post-1995, randomized, adjuvant cisplatin\u2013based trials, and it found an absolute survival benefit of 5.4% at 5 years (HR, 0.89; p=0.005) in favor of chemotherapy [Pignon JP et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2008]. The survival benefit in LACE was stage dependent: a significant benefit was observed for stages II and III, with no benefit for stage IA and a borderline benefit for stage IB. The larger-updated NSCLC Collaborative Group meta-analysis produced results concordant with those of LACE [Arriagada R et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010]. Patients with stage IB NSCLC with tumor size \u22654 cm did appear likely to benefit from adjuvant chemotherapy, according to subanalyses of 2 trials.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe strongest evidence for adjuvant chemotherapy in NSCLC is with cisplatin and vinorelbine, but other cisplatin doublets have known efficacy [Kreuter M et al. \u003Cem\u003EAnn Oncol\u003C\/em\u003E 2013]. Carboplatin is also used as adjuvant therapy despite the lack of randomized Phase 3 data to support it.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EPredictive markers of chemotherapy sensitivity remain elusive. Prospective adjuvant trials are assessing the usefulness of ERCC1\u2013RRM1, ERCC1\u2013TS, ERCC1\u2013epidermal growth factor receptor (EGFR) mutation, and BRCA1\u2013RAP80 as biomarkers.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003ETargeted agents (ie, erlotinib and gefitinib) as adjuvant therapy for patients with EGFR-activating mutations or anaplastic lymphoma kinase translocations are under investigation, and they are awaiting a trial with positive outcomes.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EIn discussing the treatment of locally advanced stage III NSCLC throughout the past 50 years, combined-modality regimens for inoperable stage III NSCLC have almost tripled the median survival, said Karen Kelly, MD, University of California Davis, Sacramento, California, USA.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EStage III NSCLC patients are a heterogeneous population with distinct clinical subsets, making management challenging, she said. Radiation therapy has been the backbone for more than 50 years. Concurrent chemotherapy and radiation has been the standard of care for fit patients since the early 1990s, doubling the 2-year survival rate compared with thoracic radiotherapy alone [Dillman RO et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 1990]. Later, daily cisplatin with radiotherapy was associated with significantly improved survival over radiation alone, although at a cost of severe nausea and\/or vomiting in \u0026gt;25% of patients [Schaake-Koning C et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 1992]. Concurrent cyclic chemotherapy (mitomycin, vindensine, and cisplatin) was superior to sequential chemotherapy on 5-year OS (16% vs 9%: p=0.03998) in a study conducted by the West Japan Lung Cancer Group [Furuse K et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 1999]. In the United States, a similar trial by the Radiation Therapy Oncology Group also showed a survival advantage for the concurrent regimen compared to sequential therapy [Curran WJ et al. \u003Cem\u003EJ Natl Cancer Inst\u003C\/em\u003E 2011]. The survival advantage appears to be the result of local regional control, said Dr. Kelly, but is associated with more esophagitis [Auperin A et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EInduction or consolidation chemotherapy has failed to show survival benefits over standard chemoradiation, but the role of consolidation therapy may depend on the chemotherapy regimen used during concurrent chemoradiotherapy, she said.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EExploiting the immune system is a promising approach to therapy in NSCLC. Tecemotide is a mucin 1 antigen-specific vaccine that induces a T-cell response; it failed to improve OS in a Phase 3 randomized study, but in the large subset of patients who received concurrent chemoradiation, the vaccine was associated with a significant 22% improvement in OS (p=0.016) [Butts C et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2014; Butts C et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2005].\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EIntegration of novel cytotoxic and targeted agents into chemoradiotherapy, and the use of higher doses and alternative schedules of radiotherapy, has yet to be proven successful.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EMartin J. Edelman, MD, University of Mexico, Albuquerque, New Mexico, USA, spoke about progress in the treatment of advanced NSCLC, noting that the value of treatment for essentially all fit patients with advanced disease is now well established in terms of significant improvement in both the quantity and quality of life. By 1990, consensus had emerged that platinum-based therapy was superior to best supportive care for patients with good performance status. Newer agents with single activity in NSCLC (i.e., vinorelbine, paclitaxel, docetaxel, gemcitabine, and irinotecan) in combination with cisplatin later proved superior to cisplatin alone on OS.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EThe equivalence of platinum doublet regimens was established in randomized, cooperative group studies, and it offered physicians a choice of regimens based on toxicity, scheduling considerations, and cost. There has been no advantage demonstrated from combining new agents, with the goal of avoiding platinum agents.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EIn patients with activating mutations of the EGFR, an EGFR tyrosine kinase inhibitor (TKI) has demonstrated superior progression-free survival over chemotherapy, but it provides no OS advantage because of crossover effects [Wu YL et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2014; Mitsudomi T et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2012; Rosell R et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2012; Yang J C-H et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2012; Zhou C et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2012; Zhou C et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2011; Maemondo M et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010; Mitsudomi T et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2010]. By 1 year, about half of patients treated with an EGFR TKI will need to move on to other therapy because of resistance, said Dr. Edelman. New agents have been designed against the mutated receptor, and they have shown significant activity in this setting with less toxicity (\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\/14578\/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\/14578\/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\/14578\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-16\u0022 class=\u0022first-child\u0022\u003EFirst-Line Treatment with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors Versus Chemotherapy in EGFR-Mutated Patients\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-26\u0022\u003EThe advent of immunotherapy has been the most dramatic change in the treatment of advanced NSCLC in the past 2 years. Anti-PD-1 and anti-PD-L-1 antibodies have demonstrated activity, some with response rates that exceed 30%, in heavily pretreated patients [Brahmer JR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2012; Topalian SL et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2012].\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\/14\/27.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?nzp50d\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?nzp50d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}