9138 POSTER Frequency of EGFR Mutations in Greek Non-Small-Cell Lung Cancer (NSCLC) Patients

2011 ◽  
Vol 47 ◽  
pp. S635
Author(s):  
G. Nasioulas ◽  
C. Efstathiadou ◽  
S. Murray ◽  
I. Dahabreh
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Nsclc Patients

Coexistence of MET exon 14 mutations with EGFR mutations in non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20636-e20636
Author(s):  
Wen-Feng Li ◽  
Jin Kang ◽  
Xu-Chao Zhang ◽  
Su Jian ◽  
Huajun Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Point Mutations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Relative Resistance ◽  
L858r Mutation ◽  
Nsclc Patients

e20636 Background: Activation of MET oncogene as the result of amplification or activation MET exon 14 mutations represents an emerging molecular target for non-small cell lung cancer (NSCLC) treatment. MET exon 14 mutations account for 1.0% in Chinese NSCLC patients. However, few data have been reported on the coexisting of MET exon 14 mutations and EGFR mutations in NSCLC. Moreover, the clinicopathological characteristics and targeted therapy of these MET/ EGFR-coexisting patients remain elusive. Methods: Next-generation sequencing was performed on the DNA of 969 patients and Sanger sequencing was conducted on cDNA of 621 patients for MET exon 14 mutations in NSCLCs. EGFR mutations were determined by direct DNA sequencing. Results: Fifteen patients harbored positive MET exon 14 mutations. Frequency of concomitant EGFR and MET exon 14 mutations was 0.2%(3/1590). 3 patients with concomitant MET exon 14 mutation and EGFR activating mutation were all female, never smokers and adenocarcinoma. Their stagings were stageⅠB (n = 1) and stage Ⅳ(n = 2). The stage ⅠB patient harboring concomitant MET exon 14 skipping and EGFR L858R mutation did not relapse 2 years after operation. The other two stage Ⅳ patients received first-line gefitinib. Case one harbored concomitant MET exon 14 point mutations (IVS13-36G > A) and EGFR exon 19 deletion, and showed resistance to gefitinib with progression free survival(PFS) of 2 weeks and overall survival(OS) of 1 month. Case two had concomitant MET exon 14 point mutations (IVS13-36G > A) and EGFR L858R mutation. Meanwhile, she also had both METamplification and c-Met overexpression at the baseline. She showed partial response (PR) to gefitinib with 3.8 months PFS. Then she was enrolled in a clinical trial (NCT02374645) to receive volitinib plus gefitinib on December 20, 2016. Initial response was good PR on January 24, 2017. Only grade 1 rash was observed. Conclusions: Coexisting MET exon 14 /EGFR mutation is an uncommon molecular event in NSCLC patients. Such coexisted patients might show relative resistance to EGFR inhibitor. However, combination of MET and EGFR inhibitors will be potentially a good strategy to overcome such a relative resistance for MET exon 14 /EGFR co-mutant patients.

The Presence of EGFR Mutations Predicts the Response in Chinese Non-Small Cell Lung Cancer Patients Treated with Erlotinib

2014 ◽  
Vol 29 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Rui-chao Li ◽  
Li-jun Zheng ◽  
Ming-hao Fang ◽  
Shi-ying Yu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iiib ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Nsclc Patients ◽  
Line Chemotherapy

Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. The upregulation of the epidermal growth factor receptor (EGFR) due to mutations has been observed in a number of cancers, and tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, which specifically target EGFR signaling, have been used to treat NSCLC patients. The presence of EGFR mutations was previously shown to confer sensitivity to TKIs. In this study, we evaluated the correlation between EGFR mutations and response to erlotinib in Chinese NSCLC patients. We recruited 36 patients with stage IIIB/IV NSCLC who had failed first-line chemotherapy, and treated them with erlotinib. We used immunohistochemistry to determine EGFR expression, and we screened for mutations using PCR analysis. We used Cox regression analysis and Kaplan-Meier curves for survival analysis. We found that 8 patients had exon 19 mutations, while 3 patients had exon 21 mutations. An Eastern Cooperative Oncology Group (ECOG) grade of 2 was a significant negative predictor of overall survival (OS). Patients with EGFR mutations showed a significantly better OS compared to those without EGFR mutations. Additionally, multivariate analysis showed that erlotinib-treated stage IV patients had a significantly longer progression-free survival (PFS) compared to stage IIIB patients. Patients with EGFR mutations also had a significantly better PFS compared to those without EGFR mutations. The overall remission rate (22.2%) and disease control rate (75%) were significantly higher compared to the rates after second-line chemotherapy (<10%). In conclusion, the presence of EGFR mutations could be a marker to predict the therapeutic efficacy of erlotinib and the prognosis in Chinese NSCLC patients.

scholarly journals RET Inhibitors in Non-Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4415
Author(s):  
Priscilla Cascetta ◽  
Vincenzo Sforza ◽  
Anna Manzo ◽  
Guido Carillio ◽  
Giuliano Palumbo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Good Tolerability ◽  
Phase Ii Studies ◽  
Nsclc Patients

RET rearrangements are observed in 1–2% of non-small-cell lung cancer (NSCLC) patients and result in the constitutive activation of downstream pathways normally implied in cell proliferation, growth, differentiation and survival. In NSCLC patients, RET rearrangements have been associated with a history of non-smoking, a higher rate of brain metastasis at initial diagnosis and a low immune infiltrate. Traditionally, RET fusions are considered mutually exclusive with other oncogenic drivers, even though a co-occurrence with EGFR mutations and MET amplifications has been observed. Cabozantinib, vandetanib and lenvatinib are the first multi-kinase inhibitors tested in RET-rearranged NSCLC patients with contrasting results. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy rates and good tolerability and they were approved for the treatment of patients with metastatic RET fusion-positive NSCLC on the bases of the results of phase II studies. Two ongoing phase III clinical trials are currently comparing selpercatinib or pralsetinib to standard first line treatments and will definitively establish their efficacy in RET-positive NSCLC patients.

scholarly journals Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients

2019 ◽  
Vol 21 (1) ◽  
pp. 66
Author(s):  
Elisa Boldrin ◽  
Giorgia Nardo ◽  
Elisabetta Zulato ◽  
Laura Bonanno ◽  
Valentina Polo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Loss Of Heterozygosity ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Genetic Characteristics ◽  
Nsclc Patients ◽  
Egfr Mutated

Liquid biopsy is currently approved for management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. However, one unanswered question is whether the rate of cell-free DNA (cfDNA)-negative samples is due to technical limitations rather than to tumor genetic characteristics. Using four microsatellite markers that map specific chromosomal loci often lost in lung cancer, we conducted a pilot study to investigate whether other alterations, such as loss of heterozygosity (LOH), could be detected in EGFR-negative cfDNA. We analyzed EGFR-mutated NSCLC patients (n = 24) who were positive or negative for EGFR mutations in cfDNA and compared the results with a second cohort of 24 patients bearing KRAS-mutated cancer, which served as a representative control population not exposed to targeted therapy. The results showed that in EGFR-negative post-tyrosine-kinase-inhibitor (TKI) cfDNAs, LOH frequency was significantly higher than in both pre- and post-TKI EGFR-positive cfDNAs. By contrast, no association between KRAS status in cfDNA and number of LOH events was found. In conclusion, our study indicates the feasibility of detecting LOH events in cfDNA from advanced NSCLC and suggests LOH analysis as a new candidate molecular assay to integrate mutation-specific assays.

Assessment of EGFR mutations in patients diagnosed of squamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18106-e18106
Author(s):  
Francisco Lobo ◽  
Manuel Domine ◽  
Federico Rojo ◽  
Yann Izarzugaza ◽  
Ana Leon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20 ◽  
Nsclc Patients

e18106 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better outcome to EGFR tyrosine kinase inhibitors than platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies with Caucasian patients have shown a prevalence of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in squamous-cell NSCLC patients from an area of influence of 500,000 habitants. Methods: Prospective mutation testing in NSCLC patients included in our institution since October 2010 to January 2012 was performed on DNA obtained from available tumor tissue and cytologic samples, using ARMS-scorpion TheraScreen EGFR 29 Mutation Test Kit (Qiagen). Results: From 218 consecutive NSCLC diagnoses, 18 (8.25%) patients showed EGFR mutations: 6 (33.3%) exon 19 deletion, 9 (50%) exon 21 mutations (7 L858R and 2 L861Q) and 3 (16.6%) cases exon 20 insertion. In the EGFR mutated population, 16 (88.88%) patients were diagnosed as adenocarcinoma and 2 (11.11%) as squamous cell carcinoma. The characteristics of these squamous cell cancer patients were: 2 male; 1 non-smoker, 1 former-smoker; 1 stage IV and 1 stage IB at diagnosis; one case exon 20 insertion and one exon 21 mutation (L858R). Conclusions: The EGFR mutation rate in squamous-cell NSCLC patients in our referral area is superior (11.17%) than previously reported, reinforcing the importance of including EGFR mutation testing in squamous-cell NSCLC population for selecting optimal therapy for these patients.

scholarly journals P3-136: A Phase II study of XL647 in non-small cell lung cancer (NSCLC) patients enriched for presence of EGFR mutations

2007 ◽  
Vol 2 (8) ◽  
pp. S737 ◽  
Author(s):  
Naiyer Rizvi ◽  
Mark Kris ◽  
Vincent Miller ◽  
Christopher Azzoli ◽  
Lee Krug ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Study ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Nsclc Patients

scholarly journals STRA6 Polymorphisms Are Associated With EGFR Mutations in Locally-Advanced and Metastatic Non-Small Cell Lung Cancer Patients

2020 ◽  
Vol 10 ◽  
Author(s):  
Saé Muñiz-Hernández ◽  
Jesús Bernardino Velázquez-Fernández ◽  
José Díaz-Chávez ◽  
Omar Mondragón-Fonseca ◽  
Yerye Mayén-Lobo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Nuclear Receptors ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Small Cell ◽  
Smoking History ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Nsclc Patients

Retinol plays a significant role in several physiological processes through their nuclear receptors, whose expression depends on retinol cytoplasmic concentration. Loss of expression of nuclear receptors and low retinol levels have been correlated with lung cancer development. Stimulated by retinoic acid 6 (STRA6) is the only described cell membrane receptor for retinol uptake. Some chronic diseases have been linked with specific polymorphisms in STRA6. This study aimed to evaluate four STRA6 single nucleotide polymorphisms (SNPs) (rs4886578, rs736118, rs351224, and rs97445) among 196 patients with locally-advanced and metastatic non-small cell lung cancer (NSCLC) patients. Genotyping, through a validated SNP assay and determined using real time-PCR, was correlated with clinical features and outcomes. NSCLC patients with a TT SNP rs4886578 and rs736118 genotype were more likely to be &gt;60 years, non-smokers, and harboring EGFR mutations. Patients with a TT genotype compared with a CC/CT SNP rs974456 genotype had a median progression-free survival (PFS) of 3.2 vs. 4.8 months, p = 0.044, under a platinum-based regimen in the first-line. Furthermore, patients with a TT rs351224 genotype showed a prolonged overall survival (OS), 47.5 months vs. 32.0 months, p = 0.156. This study showed a correlation between clinical characteristics, such as age, non-smoking history, and EGFR mutational status and oncological outcomes depending on STRA6 SNPs. The STRA6 TT genotype SNP rs4886578 and rs736118 might be potential biomarkers in locally-advanced and metastatic NSCLC patients.

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