First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer

Greenhalgh, J; Boland, Angela; Bates, Victoria; Vecchio, Fabio Maria; Dündar, Yenal; Richardson, Marty; Green, John A.

doi:10.1002/14651858.cd010383.pub3

Cited by 41 publications

(24 citation statements)

References 118 publications

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“…Non-small-cell lung cancer (NSCLC) is the first cause of cancer-related death worldwide [ 1 ]. Epidermal growth factor receptor (EGFR) activating mutations identify a subgroup of patients deriving survival benefit from tyrosine kinase inhibitors (TKIs) [ 2 ]. Therefore, clinical guidelines suggest testing all advanced non-squamous NSCLC, as well as selected squamous cell lung cancer patients, for EGFR mutations along with other oncogenic alterations in order to provide a targeted treatment.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Molecular Features of Epidermal Growth Factor Receptor (EGFR) Mutation Positive Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Tyrosine Kinase Inhibitors (TKIs): Predictive and Prognostic Role of Co-Mutations

Bironzo

Reale

Sperone

et al. 2021

Cancers

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Background: Tyrosine kinase inhibitors (TKIs) show variable efficacy in epidermal growth factor receptor mutation-positive (EGFR+) NSCLC patients, even in patients harbouring the same mutation. Co-alterations may predict different outcomes to TKIs. Methods: We retrospectively analysed all consecutive EGFR+ advanced NSCLC treated with first-line TKIs at our Institutions. NGS with a 22 genes clinical panel was performed on diagnostic specimens. PD-L1 expression was also evaluated. Results: Of the 106 analysed specimens, 59 showed concomitant pathogenic mutations. No differences in OS (mOS 22.8 vs. 29.5 months; p = 0.088), PFS (mPFS 10.9 vs. 11.2 months; p = 0.415) and ORR (55.9% vs. 68.1%; p = 0.202) were observed comparing patients without and with co-alterations. Subgroup analysis by EGFR mutation type and TKIs generation (1st/2nd vs. 3rd) did not show any difference too. No correlations of PD-L1 expression levels by co-mutational status were found. Significant associations with presence of co-alterations and younger age (p = 0.018) and baseline lymph nodes metastases (p = 0.032) were observed. Patients without concomitant alterations had a significant higher risk of bone progression (26.5% vs. 3.3%, p = 0.011). Conclusions: Pathogenic co-alterations does not seem to predict survival nor efficacy of EGFR TKIs in previously untreated advanced NSCLC.

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Section: Introductionmentioning

confidence: 99%

Clinical and Molecular Features of Epidermal Growth Factor Receptor (EGFR) Mutation Positive Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Tyrosine Kinase Inhibitors (TKIs): Predictive and Prognostic Role of Co-Mutations

Bironzo

Reale

Sperone

et al. 2021

Cancers

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“…The emergence of EGFR-TKIs at the beginning of the 21st century constituted a paradigm shift in the management of EGFR mutation-positive NSCLC, heralding an era of precision medicine. Compared with traditional cytotoxic therapies, EGFR-TKIs have improved clinical outcomes and health-related quality of life in patients with advanced disease [5]. However, acquired resistance to first-generation (e.g.…”

Section: Introductionmentioning

confidence: 99%

Osimertinib: A Review in Previously Untreated, EGFR Mutation-Positive, Advanced NSCLC

Lamb

2021

Targ Oncol

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Activating mutations in the epidermal growth factor receptor (EGFR) gene have been identified as key oncogenic drivers of non-small cell lung cancer (NSCLC). Osimertinib (Tagrisso ® ) is an orally administered, third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) that is widely approved for the first-line treatment of advanced NSCLC with activating EGFR mutations. In the pivotal phase III FLAURA trial, osimertinib significantly prolonged progression-free survival (PFS) and overall survival (OS) relative to first-generation EGFR-TKIs in patients with previously untreated, EGFR mutation-positive, advanced NSCLC. Osimertinib also significantly prolonged central nervous system (CNS) PFS in patients with CNS metastases at trial entry. Osimertinib had a generally manageable tolerability profile; the majority of adverse events considered to be possibly related to treatment were of mild to moderate severity. Osimertinib represents a valuable targeted therapeutic for use in adults with previously untreated, EGFR mutation-positive, advanced NSCLC.

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“…30,33 1631 In recent years, the clinical application of TKI to NSCLC as a heterogeneous disease with multiple genetic subsets has led to extended median survival of 3 years. 35 The EGFR protein is expressed in about 50-90% of cases of NSCLC. The two main approaches to EGFR inhibitors are the use of small-molecule inhibitors of the intracellular tyrosine kinase domain and monoclonal antibodies that block the extracellular domain of the receptor.…”

Section: Egfr Genementioning

confidence: 99%

“…Gefitinib and erlotinib are orally administered EGFR-TKIs that can compete with ATP for binding to the TK domain. 35 Uncommon EGFR mutation, such as G719X, L861Q, S768I and E709X are widely sensitive to EGFR-TKI, especially second and third generation agents. 36…”

Section: Egfr Genementioning

confidence: 99%

Correlation Epidermal Growth Factor Receptor Mutation with Non-small Cell Lung Cancer in Passive Smokers: A Review

Prameswari

Suryandari

2022

Bioscmed

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Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with an extracellular epidermal growth factor binding domain and an intracellular tyrosine kinase domain through signaling pathways to regulate cellular proliferation. Epidermal growth factor receptor binding to its ligand will result in autophosphorylation by intrinsic tyrosine kinase activity, thereby triggering multiple signal transduction cascades. Constant or sustained activation of these downstream target sequences is thought to result in a more aggressive tumor phenotype. Mutations in EGFR are associated with non-small cell lung cancer in passive smokers.

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First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer

Abstract: First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer.

Cited by 41 publications

References 118 publications

Clinical and Molecular Features of Epidermal Growth Factor Receptor (EGFR) Mutation Positive Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Tyrosine Kinase Inhibitors (TKIs): Predictive and Prognostic Role of Co-Mutations

Clinical and Molecular Features of Epidermal Growth Factor Receptor (EGFR) Mutation Positive Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Tyrosine Kinase Inhibitors (TKIs): Predictive and Prognostic Role of Co-Mutations

Osimertinib: A Review in Previously Untreated, EGFR Mutation-Positive, Advanced NSCLC

Correlation Epidermal Growth Factor Receptor Mutation with Non-small Cell Lung Cancer in Passive Smokers: A Review

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