scholarly journals Frequency of epidermal growth factor receptor (EGFR) mutations in stage IB–IIIA EGFR mutation positive non-small cell lung cancer (NSCLC) after complete tumour resection

2019 ◽  
Vol 30 ◽  
pp. v589
Author(s):  
M. Tsuboi ◽  
R.S. Herbst ◽  
T. John ◽  
C. Grohe ◽  
M. Majem ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Tumour Resection ◽  
Small Cell Lung ◽  
Complete Tumour Resection ◽  
Complete Tumour ◽  
Epidermal Growth

Epidermal Growth Factor Receptor Mutations in Plasma DNA Samples Predict Tumor Response in Chinese Patients With Stages IIIB to IV Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (16) ◽  
pp. 2653-2659 ◽  
Author(s):  
Hua Bai ◽  
Li Mao ◽  
hang Shu Wang ◽  
Jun Zhao ◽  
Lu Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Tumor Response ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
Plasma Dna ◽  
Small Cell Lung ◽  
Epidermal Growth

Purpose Mutations in the epidermal growth factor receptor (EGFR) kinase domain can predict tumor response to tyrosine kinase inhibitors (TKIs) in non–small-cell lung cancer (NSCLC). However, obtaining tumor tissues for mutation analysis is challenging. We hypothesized that plasma-based EGFR mutation analysis is feasible and has value in predicting tumor response in patients with NSCLC. Patients and Methods Plasma DNA samples and matched tumors from 230 patients with stages IIIB to IV NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using denaturing high-performance liquid chromatography. We compared the mutations in the plasma samples and the matched tumors and determined an association between EGFR mutation status and the patients' clinical outcomes prospectively. Results In 230 patients, we detected 81 EGFR mutations in 79 (34.3%) of the patients' plasma samples. We detected the same mutations in 63 (79.7%) of the matched tumors. Sixteen plasma (7.0%) and fourteen tumor (6.1%) samples showed unique mutations. The mutation frequencies were significantly higher in never-smokers and in patients with adenocarcinomas (P = .012 and P = .009, respectively). In the 102 patients who failed platinum-based treatment and who were treated with gefitinib, 22 (59.5%) of the 37 with EGFR mutations in the plasma samples, whereas only 15 (23.1%) of the 65 without EGFR mutations, achieved an objective response (P = .002). Patients with EGFR mutations had a significantly longer progression-free survival time than those without mutations (P = .044) in plasma. Conclusion EGFR mutations can be reliably detected in plasma DNA of patients with stages IIIB to IV NSCLC and can be used as a biomarker to predict tumor response to TKIs.

scholarly journals The Role of Mutation Status of the Epidermal Growth Factor Receptor Gene In Advanced Non–Small Cell Lung Cancer

Medicina ◽  
2012 ◽  
Vol 48 (4) ◽  
pp. 25 ◽  
Author(s):  
Neringa Vagulienė ◽  
Marius Žemaitis ◽  
Valdas Šarauskas ◽  
Astra Vitkauskienė ◽  
Skaidrius Miliauskas
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Positive Group ◽  
Epidermal Growth ◽  
Never Smokers

Objective. The aim of this study was to examine the prevalence of epidermal growth factor receptor (EGFR) gene mutations among patients with advanced nonsquamous non–small cell lung cancer (NSCLC) treated in our institution and to evaluate the associations between EGFR mutations and clinicopathological characteristics. Materials and Methods. A total of 103 patients with NSCLC were examined from April 2010 to September 2011. The patients were screened for EGFR mutations in exons 19 and 21 using sequence analysis. Results. EGFR mutations were detected in 10 patients (9.71%): 23.1% of women and 5.2% of men (P<0.05), 31.8% of never-smokers and 4.7% of smokers (P<0.05), and 12.3% of patients with adenocarcinomas and 6.25% of patients with large cell carcinomas (P>0.05). Eight mutations (80.0%) were found in exon 21: 7 patients had the L858R mutation and 1 patient had the L861G mutation. Two mutations (20.0%) were found in exon 19: 1 patient had the L747-A748 deletion and 1 patient had the L747-A750insE deletion. The overall response rate was significantly greater in the EGFR mutation-positive group than in the EGFR mutation-negative or control groups (P<0.05). The median progression-free survival in the EGFR mutation-negative group and the control group that received systemic standard chemotherapy was 5.6 months (95% CI, 4.3 to 7.0) and 5.3 months (95% CI, 4.9 to 5.7), respectively, but it was not achieved in the EGFR mutation-positive group that received EGFR tyrosine kinase inhibitors (P<0.05). Conclusions. The frequency of EGFR mutations in our patients with nonsquamous NSCLC was found to be similar to that reported in Europe. EGFR mutations were more frequent in women and never-smokers

Epidermal Growth Factor Receptor Mutations and Gene Amplification in Non–Small-Cell Lung Cancer: Molecular Analysis of the IDEAL/INTACT Gefitinib Trials

2005 ◽  
Vol 23 (31) ◽  
pp. 8081-8092 ◽  
Author(s):  
Daphne W. Bell ◽  
Thomas J. Lynch ◽  
Sara M. Haserlat ◽  
Patricia L. Harris ◽  
Ross A. Okimoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Molecular Markers ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
The Ideal

Purpose Most cases of non–small-cell lung cancer (NSCLC) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor (EGFR), but the predictive value of these mutations has not been defined in large clinical trials. The goal of this study was to determine the contribution of molecular alterations in EGFR to response and survival within the phase II (IDEAL) and phase III (INTACT) trials of gefitinib. Patients and Methods We analyzed the frequency of EGFR mutations in lung cancer specimens from both the IDEAL and INTACT trials and compared it with EGFR gene amplification, another genetic abnormality in NSCLC. Results EGFR mutations correlated with previously identified clinical features of gefitinib response, including adenocarcinoma histology, absence of smoking history, female sex, and Asian ethnicity. No such association was seen in patients whose tumors had EGFR amplification, suggesting that these molecular markers identify different biologic subsets of NSCLC. In the IDEAL trials, responses to gefitinib were seen in six of 13 tumors (46%) with an EGFR mutation, two of seven tumors (29%) with amplification, and five of 56 tumors (9%) with neither mutation nor amplification (P = .001 for either EGFR mutation or amplification v neither abnormality). Analysis of the INTACT trials did not show a statistically significant difference in response to gefitinib plus chemotherapy according to EGFR genotype. Conclusion EGFR mutations and, to a lesser extent, amplification appear to identify distinct subsets of NSCLC with an increased response to gefitinib. The combination of gefitinib with chemotherapy does not improve survival in patients with these molecular markers.

Prospective analysis of the epidermal growth factor receptor gene mutations in non-small cell lung cancer in Japan

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7077-7077 ◽  
Author(s):  
N. Morikawa ◽  
A. Inoue ◽  
T. Suzuki ◽  
T. Fukuhara ◽  
S. Suzuki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Egfr Mutation ◽  
Response Rate ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Nsclc Patients

7077 Background: Previous clinical trials have revealed that gefitinib is more likely to be effective in non-small cell lung cancer (NSCLC) with activating somatic mutations of epidermal growth factor receptor (EGFR). Most of those reports evaluated NSCLC patients who had post-operative recurrence and then received gefitinib retrospectively using their surgical specimens. However, many NSCLC patients are inoperable at diagnosis. Thus we conducted this study to examine EGFR mutation status by diagnostic tumor samples before gefitinib treatment and investigate the correlation between EGFR mutation and the efficacy of gefitinib. Methods: We prospectively evaluated various tumor samples obtained from NSCLC patients who had never received gefitinib for EGFR mutations in exon 18–23. For patients treated with gefitinib after the examination of EGFR mutations, the response to gefitinib was also evaluated. Results: From June 2004 to November 2005, 91 patients with advanced or post-operative recurrent NSCLC enrolled onto this study and 104 tumor samples were obtained from transbronchial biopsies, effusions, as well as surgical specimens. Thirty-two mutations including deletions in exon 19 in 23 patients and L858R in 9 patients were detected among those 91 patients; 30 in 81 adenocaricinoma, 1 in 2 adenosquamous cell carcinoma, and 1 in 5 large cell carcinoma. The mutations were found more frequently in female (51.9%) than male (12.8%), in never smoker (52.0%) than smoker (14.6%). Response rate of gefitinib in patients with EGFR mutations was 65.0% (13 of 20) compared to 37.5% (3 of 8) in patients without mutations. Among 7 patients with EGFR mutations who were examined multiple tumor samples, 3 had the discrepancy of EGFR gene status between different samples obtained at different time points, suggesting genetic heterogeneity of their tumors. The EGFR status of the most recent samples is likely to be correlated to the response to gefitinib. Conclusions: The EGFR mutation analysis was possible not only from surgical specimens but also from daily available diagnostic samples. For patients with EGFR mutations, gefitinib could achieve a promising high response rate. We propose to examine the most recent tumor samples to predict the sensitivity to gefitinib reliably. No significant financial relationships to disclose.

Detection of epidermal growth factor receptor gene mutations in cytology specimens from patients with non-small cell lung cancer utilising high-resolution melting amplicon analysis

2007 ◽  
Vol 61 (4) ◽  
pp. 487-493 ◽  
Author(s):  
G D Smith ◽  
B E Chadwick ◽  
C Willmore-Payne ◽  
J S Bentz
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Mutation Status ◽  
Epidermal Growth ◽  
Exon 19

Background:Activating epidermal growth factor receptor (EGFR) mutations have been implicated in non-small cell lung cancer (NSCLC), and have also been clinically correlated with patient sensitivity to targeted EGFR inhibitors.Aim:To describe a technique for determining EGFR mutation status on archival fine needle aspirate (FNA) specimens from advanced NSCLC patients.Methods:Eleven archival FNA slides from patients with advanced NSCLC were examined for diagnostic material to identify tumour cell-enriched regions. EGFR mutation status was determined using a slide-scrape DNA extraction protocol of selected tumour cell regions on the smear slides, followed by real time PCR and high resolution melt analysis (HRMAA) of EGFR exons 18, 19, 20, and 21, followed by sequence analysis.Results:All DNA samples were successfully amplified by PCR. Three adenocarcinoma patient samples contained EGFR mutations in exon 19 (L747-P753insS). One of the three had an additional exon 19 mutation (A755D).Conclusions:Archival cytology slides from patients with NSCLC can be used to determine EGFR mutation status by PCR, HRMAA, and sequencing. The ability to use archival cytology slides greatly increases the potential material available for molecular analysis in diagnosis and selection of patients for targeted therapeutic agents.

scholarly journals Outcomes of Afatinib in Non-small Cell Lung Cancer Patients Harboring Uncommon Epidermal Growth Factor Receptor Mutations

2020 ◽  
Author(s):  
Kewei Zhao ◽  
Shanliang Hu ◽  
Wei Dong ◽  
Wei Chen ◽  
Yipeng Song ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Treatment Response ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Pooled Analysis ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Epidermal Growth

Abstract Background: Uncommon epidermal growth factor receptor (EGFR) mutations are a heterogeneous population of molecular alterations, and clinical data on the outcomes of afatinib in patients with non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations are limited. The purpose of this pooled analysis was to investigate the clinicopathological features of uncommon EGFR mutations in patients and the treatment response and survival associated with afatinib treatment.Methods: We performed a literature search in the NCBI PubMed database to identify relevant articles and completed a pooled analysis based on 37 related published studies.The relationship between clinical characteristics, EGFR mutation type and treatment response were analyzed using univariate chi-square analysis, and survival analysis was performed using the Kaplan–Meier method.Results: A total of 57 patients were included in this pooled analysis. The objective response rate to treatment with afatinib was 46.4%, with a median PFS of 7.0 months.Patients with a single uncommon EGFR mutation are more likely than patients with multiple mutations to show a good tumor response after receiving afatinib (ORR: 57.9% vs 26.3%, HR: 0.260, 95% CI: 0.078-0.869, p=0.029). Similarly, patients with a single uncommon EGFR mutation had a longer PFS than patients with multiple mutations (mPFS: 10.0 months vs 3.6 months, HR: 2.906, 95% CI: 1.496-5.646, p=0.002). In addition, for patients with a good treatment response, the PFS was also longer (HR: 2.902, 95% CI: 1.522-5.533, p=0.001).Conclusions: For patients with uncommon mutations, the outcomes of afatinib is worse than that of patients with classic sensitive mutations but higher than that of EGFR wild-type patients. Uncommon EGFR mutations contain various subtypes, and different subtypes have different sensitivities to afatinib. Patients with a single rare mutation show better treatment responses to afatinib and better prognoses than patients with multiple mutations.

First-Line Gefitinib for Patients With Advanced Non–Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations Without Indication for Chemotherapy

2009 ◽  
Vol 27 (9) ◽  
pp. 1394-1400 ◽  
Author(s):  
Akira Inoue ◽  
Kunihiko Kobayashi ◽  
Kazuhiro Usui ◽  
Makoto Maemondo ◽  
Shoji Okinaga ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Nucleic Acid ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Epidermal Growth

Purpose This multicenter phase II study was undertaken to investigate the efficacy and feasibility of gefitinib for patients with advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations without indication for chemotherapy as a result of poor performance status (PS). Patients and Methods Chemotherapy-naïve patients with poor PS (patients 20 to 74 years of age with Eastern Cooperative Oncology Group PS 3 to 4, 75 to 79 years of age with PS 2 to 4, and ≥ 80 years of age with PS 1 to 4) who had EGFR mutations examined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method were enrolled and received gefitinib (250 mg/d) alone. Results Between February 2006 and May 2007, 30 patients with NSCLC and poor PS, including 22 patients with PS 3 to 4, were enrolled. The overall response rate was 66% (90% CI, 51% to 80%), and the disease control rate was 90%. PS improvement rate was 79% (P < .00005); in particular, 68% of the 22 patients improved from ≥ PS 3 at baseline to ≤ PS 1. The median progression-free survival, median survival time, and 1-year survival rate were 6.5 months, 17.8 months, and 63%, respectively. No treatment-related deaths were observed. Conclusion This is the first report indicating that EGFR mutation-positive patients with extremely poor PS benefit from first-line gefitinib. Because there previously has been no standard treatment for these patients with short life expectancy other than best supportive care, examination of EGFR mutations as a biomarker is recommended in this patient population.

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