Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers

Costa, Daniel B.; Kobayashi, Susumu; Tenen, Daniel G.; Huberman, Mark S.

doi:10.1016/j.lungcan.2007.05.017

Cited by 150 publications

(107 citation statements)

References 64 publications

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“…60 Somatic mutations in the tyrosine kinase domain of the EGFR gene in NSCLC are associated with clinical responses to EGFR inhibitors gefitinib and erlotinib. 61,62 The therapeutic potential of EGFR inhibition was demonstrated by the Iressa Pan-Asia Study that analyzed Asian nonsmoking patients with adenocarcinoma histology treated with first-line gefitinib. 63 It confirmed an improvement in progression-free survival compared with chemotherapy.…”

Section: Molecular Targetsmentioning

confidence: 99%

Epidemiology of Lung Cancer

McErlean¹,

Ginsberg

2011

Seminars in Roentgenology

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Section: Molecular Targetsmentioning

confidence: 99%

Epidemiology of Lung Cancer

McErlean¹,

Ginsberg

2011

Seminars in Roentgenology

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“…EGFR-TKIs show an impressive response rate in EGFR-mutated patients with 70% having an objective response to treatment (5)(6)(7)(8). Unfortunately, all patients acquire resistance over time.…”

mentioning

confidence: 99%

The role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer

Jakobsen

Demuth

Sørensen³

et al. 2016

Transl. Lung Cancer Res.

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Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and resistance to lung cancer therapy Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death worldwide. The 5-year survival remains at 10-15% despite advances in treatment options.Erlotinib, a TKI targeting EGFR, was initially explored as a second-line treatment in NSCLC patients progressing on standard chemotherapy. Survival was prolonged compared to placebo (1). However, erlotinib was soon discovered to be especially efficient in patients with a mutation in the tyrosine kinase domain of EGFR. These patients are nowThe role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer Correspondence to: Anders Lade Nielsen. Department of Biomedicine, Bartholin Building, Aarhus University, DK-8000, Aarhus C, Denmark.Email: aln@biomed.au.dk.Abstract: Inhibition of the epidermal growth factor receptor (EGFR) is an important strategy when treating non-small cell lung cancer (NSCLC) patients. However, intrinsic resistance or development of resistance during the course of treatment constitutes a major challenge. The knowledge on EGFRdirected tyrosine kinase inhibitors (TKIs) and their biological effect keeps increasing. Within the group of patients with EGFR mutations some benefit to a much higher degree than others, and for patients lacking EGFR mutations a subset experience an effect. Up to 70% of patients with EGFR mutations and 10-20% of patients without EGFR mutations initially respond to the EGFR-TKI erlotinib, but there is a severe absence of good prognostic markers. Despite initial effect, all patients acquire resistance to EGFR-TKIs.Multiple mechanisms have implications in resistance development, but much is still to be explored. Epithelial to mesenchymal transition (EMT) is a transcriptionally regulated phenotypic shift rendering cells more invasive and migratory. Within the EMT process lays a need for external or internal stimuli to give rise to changes in central signaling pathways. Expression of mesenchymal markers correlates to a bad prognosis and an inferior response to EGFR-TKIs in NSCLC due to the contribution to a resistant phenotype. A deeper understanding of the role of EMT in NSCLC and especially in EGFR-TKI resistance-development constitute one opportunity to improve the benefit of TKI treatment for the individual patient. Many scientific studies have linked the EMT process to EGFR-TKI resistance in NSCLC and our aim is to review the role of EMT in both intrinsic and acquired resistance to EGFR-TKIs.Keywords: Epidermal growth factor receptor (EGFR); epithelial to mesenchymal transition (EMT); non-small cell lung cancer (NSCLC); tyrosine kinase inhibitor (TKI)

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“…Indeed, even if EGFR-mutant NSCLC usually respond well to EGFR-TKI, every patient finally progresses, and median progressionfree survival does not exceed 10 to 18 months [19]. Acquired resistance is defined by systemic progression of the disease in accordance with RECIST (response evaluation criteria in solid tumors) or WHO (world health organization) criteria appearing while on continuous treatment with erlotinib or gefitinib for patients with EGFR-mutant NSCLC or after a previous clinical benefit for more than 12 weeks [20].…”

Section: Todaymentioning

confidence: 99%

Advanced non-squamous non-small-cell lung cancer: who and when should be biologically screened today? Tomorrow?

Tomasini

Greillier

2012

Curr Respir Care Rep

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There is a need for identification of prognostic and/or predictive biomarkers to improve the choice of therapeutic strategies for patients diagnosed with advanced nonsquamous NSCLC. Only two predictive biomarkers have been validated: EGFR mutations and EML4-ALK translocations. These markers can be used to predict the response to targeted therapy (erlotinib and gefitinib or crizotinib). Several emerging biomarkers are being studied in ongoing clinical trials to predict the response of new targeted therapy or resistance to EGFR-TKI or ALK inhibitors. Every patient diagnosed with advanced NSCLC should be screened for prognostic and predictive biomarkers. There is no longer any place for clinical screening of patients potentially eligible for biological analysis. The ASCO recommends analysis of biomarkers at the time of diagnosis. However, there is evidence supporting the need for serial analysis. The purpose of these data and recommendations is to individualize therapeutic strategies for patients with advanced NSCLC and to improve their survival.

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Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers

Cited by 150 publications

References 64 publications

Epidemiology of Lung Cancer

Epidemiology of Lung Cancer

The role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer

Advanced non-squamous non-small-cell lung cancer: who and when should be biologically screened today? Tomorrow?

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