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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\u003EFour to six cycles of platinum-based doublet chemotherapy remains the standard treatment protocol for most patients with advanced non-small cell lung cancer (NSCLC). Longer treatment does not appear to increase overall or progression-free survival and may lead to toxicity issues and reduced quality of life. This article discusses the current state of knowledge concerning treatment for NSCLC patients without a targetable (driver) mutation, the impact of oncogenic drivers on treatment of NSCLC, as well as the use of maintenance therapy for patients with cancer as a way to delay disease progression and improve survival.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERespiratory Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECancer\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERespiratory Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECancer\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EFour to six cycles of platinum-based doublet chemotherapy remains the standard treatment protocol for most patients with advanced non-small cell lung cancer (NSCLC). Longer treatment does not appear to increase overall (OS) or progression-free survival (PFS) and may lead to toxicity issues and reduced quality of life (QoL). Frances A. Shepherd, MD, FRCPC, University of Toronto, Princess Margaret Hospital, Toronto, Ontario, Canada, discussed the current state of knowledge concerning treatment for NSCLC patients without a targetable (driver) mutation.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAfter an initial diagnosis of NSCLC some of the issues in the selection of treatment of first-line therapy include the impact of histology on the selection of a regimen, treatment of the elderly, addition of a targeted agent, and whether to use chemotherapy or a targeted agent. Even with full immunohistochemistry testing, subtyping may not be possible in 10% to 15% of cases, but testing can be used to identify patients with squamous histology in whom bevacizumab is associated with increased toxicity (hemoptysis) and pemetrexed has inferior results [Scagliotti GV et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003ETraditionally, older patients (\u0026gt;70 years) have been treated with monotherapy, but recent studies have shown that platinum-based doublet chemotherapy is associated with significantly (p\u0026lt;0.0001) improved survival benefits (10.3 months) compared with vinorelbine or gemcitabine monotherapy (6.2 months) [Quoix E et al. \u003Cem\u003ELancet\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe addition of targeted agents, like bevacizumab and cetuximab, to first-line chemotherapy doublets can add survival benefits in selected (nonelderly fit patients) but comes with an increased risk of treatment-related deaths [Sandler AB et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2006]. Routine initial tissue-based assessment of epidermal growth factor receptor (EGFR) mutations in NSCLC patients followed by treatment of mutation-positive patients with EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib or gefitinib, improves PFS (p\u0026lt;0.0001) compared with chemotherapy (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Rosell R et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2012]. In patients with advanced pulmonary adenocarcinoma who are negative for the mutation, PFS is significantly longer (p\u0026lt;0.001) with chemotherapy versus gefitinib [Mok TS et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009].\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\/13\/6\/32\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022PFS in Intention to Treat Population\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1417721926\u0022 data-figure-caption=\u0022PFS in Intention to Treat Population\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/32\/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\/13\/6\/32\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\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\/13\/6\/32\/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\/13460\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 attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EPFS in Intention to Treat Population\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced from Rosell R et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. \u003Cem\u003ELancet Oncology\u003C\/em\u003E 2012;13(3):239\u2013246. With permission from Elsevier.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003ECrizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, has been approved for use in NSCLC patients with ALK mutations. In this patient group, it significantly improves (p\u0026lt;0.0001) PFS compared with chemotherapy [Shaw A et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2013]\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EA number of molecular tests have been put forward as prognosticators to select or exclude chemotherapy such as KRAS and ERCC1 in NSCLC patients, but the results of these tests remain inconclusive. Prof. Shepherd cautioned that to date \u201cthere is no molecular test to select or exclude chemotherapy for patients without a driver mutation.\u201d\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EPaul A. Bunn, Jr., MD, University of Colorado School of Medicine, Denver, Colorado, USA, discussed the impact of oncogenic drivers on treatment of NSCLC.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EIn 2004, two groups identified specific mutations in the EGFR gene, which correlate with clinical responsiveness to the TKIs gefitinb and erlotinib. These mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor. Screening for such mutations in lung cancers may identify patients who will have a response to gefitinib [Pao W et al. \u003Cem\u003EProc Natl Acad Sci\u003C\/em\u003E 2004; Lynch TJ et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2004; Paez JG et al. \u003Cem\u003EScience\u003C\/em\u003E 2004]. In the IPASS trial, gefitinib was shown to prolong PFS in patients with EGFR mutations but not in patients without EGFR mutations and to improve both QoL and symptoms [Thongprasert S et al. \u003Cem\u003EJ Thorac Oncol\u003C\/em\u003E 2011]. Several other trials have gone on to show that use of an oral TKI leads to superior response (but not OS) compared with platinum doublet chemotherapy as first-line treatment for EGFR mutant patients.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EBoth European and American oncology associations guidelines recommend that patients with advanced NSCLC be tested for active EGFR mutations before receiving first-line therapy and that the choice of an EGFR TKI or chemotherapy should be based on the presence or absence of EGFR mutations.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EPhase 3 trials have shown the advantages of using crizotinib to treat NSCLC in patients who are fluorescence \u003Cem\u003Ein situ\u003C\/em\u003E hybridization positive [Shaw A et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2013]. Guidelines recommend ALK testing for NSCLC patients with an adenocarcinoma component and the use of crizotinib in those patients testing positive [Lindeman NI et al. \u003Cem\u003EJ Thorac Oncol\u003C\/em\u003E 2013]. Dr. Bunn sees the use of more oncogenic drivers in the future as the cost of testing decreases and the reliability of the tests improve.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003ELuis Paz-Ares, MD, PhD, Hospital Universitario Virgen del Roc\u00edo, Instituto de Investigaciones Biom\u00e9dicas de Sevilla, Seville, Spain, advocated maintenance therapy for patients with cancer as a way to delay disease progression and improve survival.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EWhen treatment is withdrawn or interrupted in patients with advanced gastrointestinal stromal tumors (GIST) treated with imatinib, there is a high risk of rapid disease progression (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [Le Cesne A et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cdiv id=\u0022F2\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\/13\/6\/32\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effects of Imatinib Withdrawal in GIST Patients\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1417721926\u0022 data-figure-caption=\u0022Effects of Imatinib Withdrawal in GIST Patients\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/32\/F2.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\/13\/6\/32\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\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\/13\/6\/32\/F2.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\/13461\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 attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-15\u0022 class=\u0022first-child\u0022\u003EEffects of Imatinib Withdrawal in GIST Patients\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced from Le Cesne A et al. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. \u003Cem\u003ELancet Oncology\u003C\/em\u003E 2010;11(10):942\u2013949. With permission from Elsevier.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-16\u0022\u003EProf. Paz-Ares recommends using a continuation approach with platinum doublet chemotherapy or a nonplatinum agent or switching to a cytotoxic agent that has not been used previously [Stinchcombe TE et al. \u003Cem\u003EJ Thorac Oncol\u003C\/em\u003E 2009]. Outcomes with either protocol are similar, but maintenance therapy following induction therapy should be started before signs of disease progression. Shorter courses are associated with less toxicity than longer, but QoL advantages are similar for both approaches [Smith IE et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2001].\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EBoth pemetrexed and erlotinib are well tolerated and lead to improved PFS and OS when used as maintenance or switch therapy in patients with NSCLC [Ciuleanu T et al. \u003Cem\u003ELancet\u003C\/em\u003E 2009; Cappuzzo F et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2010]. Pemetrexed is effective as maintenance therapy even when previously used during induction therapy but toxicity is moderately elevated, particularly neutropenia and fatigue [Paz-Ares LG et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2012]. Prof. Paz-Ares noted that if there is a good response to an agent in the induction phase, there is usually no added benefit to switching to a new agent during the maintenance phase.\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EThere are drawbacks to maintenance. It usually does not improve QoL, there are toxicity issues to be considered, and it is not appropriate for patients with the ECOG PS of 2. Also, the expense-benefit cost ratio is yet to be studied. Maintenance therapy is also better for patients with nonsquamous histology. Prof. Paz-Ares said that he is not sure if it should be given to every patient but he does believe that it should be offered as an option for patients whose disease has not progressed after four to six cycles of first-line chemotherapy. As findings are inconclusive at this point, further research is warranted.\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\/32.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?nznwsq\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?nznwsq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}