Prevalence of EGFR mutations in the Peruvian population: Study in a large cohort of patients with NSCLC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13076-e13076 ◽  
Author(s):  
Luis Mas ◽  
Christian Piscocha ◽  
Jose Landa ◽  
Carlos Roe ◽  
Eduardo Roe ◽  
...  
Keyword(s):  
Latin American ◽  
Small Sample ◽  
Large Cohort ◽  
Egfr Mutations ◽  
Reference Laboratory ◽  
Mutational Status ◽  
Exon 20 ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Exon 19

e13076 Background: The evaluation of EGFR mutational status of the EGFR in non-small cell lung cancer (NSCLC) is crucial to select the adequate targeted therapy and to know the outcome of patients. Previous studies in relative small sample sizes have described a higher prevalence of EGFR mutations in Peruvian population than other Latin American countries. Our aim in this study was to determine the prevalence of activating and resistance mutations of EGFR in a large cohort of Peruvian patients. Methods: We profiled metastatic tumor samples from 847 NSCLC patients for known EGFR mutations associated to sensitivity or resistance EGFR inhibitors, including exon 18 (G719X), exon 19 (deletions), exon 20 (T790M, S768I and insertions) and exon 21 (L858R). All samples were centrally tested in reference laboratory (Roe laboratory, Lima-Peru). Results: A total of 847 samples were profiled for EGFR mutational status. EGFR mutations were present in 32.9% of cases (n = 279). In regard to distribution of mutations in cases EGFR mutated, G719X (in exon 18) was present in 2.5% (n = 7); deletions in exon 19 had a frequency of 58.4% (n = 163). Mutations in exon 20 were present in 9.7% (n = 27). In patients with exon 20 mutated, 14 cases had insertions, 9 cases had the mutation T790M and 4 cases had the mutation S768I. Mutation L858R (exon 21) was present in 34.1% (n = 95) of cases. Coexistence of two mutations were present in exon 18/exon 20 (n = 1), exon 19/exon 20 (n = 7) and exon 20/ exon 21 (n = 5). In tumors with EGFR mutated. The sensible profile for EGFR tyrosine kinase inhibitors (TKI´s) was present in 96.8% of cases (n = 138). Conclusions: We have a high prevalence of EGFR mutations compared than Caucasian or other Hispanic cohorts. It has relevance in the Peruvian public health because more efforts should be done to screen NSCLC patients for EGFR mutations.

Prevalence of EGFR mutations in non-small cell lung cancer (NSCLC) smoker patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21015-e21015 ◽  
Author(s):  
Yann Izarzugaza ◽  
Manuel Domine ◽  
Federico Rojo ◽  
Victoria Casado ◽  
Ana Leon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20 ◽  
Egfr Mutated ◽  
Exon 19

e21015 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better response to tyrosine kinase inhibitors compared to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies in caucasian population have reported a frequency of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in caucasian smoker patients with NSCLC. 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 deletions, 9 (50%) exon 21 mutations (7 cases L858R and 2 cases L861Q) and 3 (16.6%) exon 20 insertions. In the EGFR-mutated patients, 13 (72.25%) were never-smoker and 5 (27.7%) were smoker (3 current-smoker and 2 former-smoker). The EGFR-mutated smoker population showed the following characteristics: 3 female, 2 male; 4 adenocarcinoma, one squamous cell carcinoma; 3 stage IV, 2 stage IA at diagnosis; 1 (20%) case EGFR deletion exon 19, 1 (20%) case insertion exon 20 and 3 patients (60%) mutation exon 21 (2, L858R and 1, L861Q). Conclusions: The EGFR mutation rate in NSCLC smoking patients in our referral area is superior (27.7%) than previously reported, reinforcing the importance of including EGFR mutation testing in NSCLC smoking population for the correct management of these patients.

Study of anlotinib combined with icotinib as the first-line treatment in non-small cell lung cancer (NSCLC) patients harboring activating EGFR mutations (ALTER-L004).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9573-9573
Author(s):  
Dingzhi Huang ◽  
Diansheng Zhong ◽  
Cuiying Zhang ◽  
Yan Zhang ◽  
Yanhong Shang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Locally Advanced ◽  
Egfr Mutations ◽  
Line Treatment ◽  
Coronary Syndrome ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Exon 19

9573 Background: Anti-angiogenic monoclonal antibodies plus EGFR TKIs have previously shown to prolong PFS in patients with EGFR-mutated NSCLC (JO25567 and NEJ026). Unlike bevacizumab, anlotinib is more convenient with orally administered and can inhibit more targets. Monotherapy using anlotinib has significantly prolonged median PFS and OS compared with the placebo values for third-line treatment or beyond in advanced NSCLC. We conducted a study to investigate the activity of anlotinb combined with icotinib, an oral EGFR TKI. Methods: This is a prospective, single-arm, multicenter clinical trial. Patients with locally advanced and/or metastatic IIIB, IIIC or IV non-squamous NSCLC are enrolled. Patients with EGFR exon 19 deletion and/or exon 21 L858R mutation who have not received prior therapies are eligible. The regimen consists of anlotinib (12 mg p.o, qd, day 1 to 14 every 21-day cycle) and icotinib (125mg p.o, tid). The primary endpoint is PFS. Secondary endpoints are OS, ORR, DCR and safety. Results: Between Jul 2018 and Dec 2019, 35 patients were enrolled in five centers and treated with anlotinb and icotinib. At data cutoff (Jan 7, 2020), patients were followed up for a median of 6.01 months.32 tumors were analyzed with 30 evaluable. Preliminary efficacy results: ORR was 59% (0 CR, 19 PR), DCR was 88% (0 CR, 19 PR, 9 SD). 26 patients are still receiving treatment and the longest exposure was 14 cycles. 10 (67%) of 15 patients with exon 19 deletions and 9 (53%) of 17 patients with L858R mutations achieved an objective response. 18 patients harbored aberrations in additional oncogenic drivers (PIK3CA or AKT1) and/or tumor suppressors (TP53, RB1, and PTEN) with an ORR of 72%. Upon analyses, AEs were observed in 97% (34/35) of patients. No Gr 5 AEs were reported. The most common Grade 3 AEs were hypertension (6 [ 17% ]), hypertriglyceridemia (2 [6% ]), diarrhea (1 [ 3% ]), hyperuricemia (1 [ 3% ]), hand and foot skin reaction (1 [3%]), asthenia (1 [3%]), and acute coronary syndrome (1 [ 3% ]). Hypertriglyceridemia was the only grade 4 AE (2 [ 6% ]). Three patients had to adjust treatment dosage. Conclusions: The strategy of anlotinib plus icotinib showed encouraging efficacy for previously untreated, EGFR-mutated advanced NSCLC patients. The combination was well tolerated and the AEs were manageable. The follow-up time is not sufficient and the PFS and OS outcomes need further evaluation. Clinical trial information: NCT03736837 .

Prevalence of uncommon epidermal growth factor receptor (EGFR) alterations detected in circulating tumor DNA (ctDNA) of non-small cell lung cancer (NSCLC) patients from East Asia.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21608-e21608
Author(s):  
Beung-Chul AHN ◽  
Herbert H. F. Loong ◽  
Oscar Siu-Hong Chan ◽  
Michelle Mei Lin Lee ◽  
Steven R. Olsen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
East Asia ◽  
East Asian ◽  
Small Cell ◽  
Braf V600e ◽  
Egfr Mutations ◽  
Synonymous Mutations ◽  
Exon 20 ◽  
Nsclc Patients ◽  
Exon 19

e21608 Background: EGFR is the most commonly altered biomarker in East Asian NSCLC patients. Common driver mutations (L858R or exon 19 deletions (del)) are the focus of conventional hotspot testing which may overlook less common activating alterations such as single nucleotide variants (SNVs) in the tyrosine kinase or extracellular domain as well as exon 20 insertions (ins). We investigated the prevalence of uncommon EGFR mutations in ctDNA from NSCLC patients in East Asia tested by a commercially available comprehensive next generation sequencing (NGS) assay (Guardant360). This assay identifies SNVs, ins and del, fusions, and amplifications (amp), with complete exon sequencing of EGFR. Methods: Guardant360 test results from Hong Kong, Korea, Japan, Taiwan, and Southeast Asia were reviewed (cut-off December 2019). We identified cases with a diagnosis of “lung cancer,” excluding pure squamous, small cell, neuroendocrine, carcinoid and sarcomatoid histology. Patients enrolled in certain prospective clinical trials were excluded at the investigators’ request. Clinically relevant biomarkers were mutations in EGFR, BRAF (V600E), ERBB2, or KRAS; MET amp or exon 14 skipping; and ALK, ROS1, or RET fusions. Uncommon EGFR mutations were defined as those other than L858R, exon 19 del, or resistance SNV in codons 790-797; synonymous mutations and amp were excluded. Results: Plasma from 820 non-squamous NSCLC patients was tested. Samples came from 436 women and 384 men, median age 61 years. ctDNA was identified in samples from 701 patients (85% detection rate). Alterations in at least one clinically relevant gene were detected in 75% of the ctDNA positive cases: EGFR (54%), KRAS (8%), ALK (5%), ERBB2 (5%), RET (2%), MET (2%), BRAF (1%), ROS1 ( < 1%). Uncommon EGFR alterations were found in 115 samples (16%), with 63 (9%) potentially actionable (exon 19 ins (1); exon 20 ins (22); activating SNV (40), some with multiple mutations, including L718Q (6), L718V (5), G719A (5), L861Q (5), S768I (4), and others) and 52 (7%) variants of unknown significance. Uncommon EGFR mutations were the only clinically relevant biomarker in 53 samples (8%). Conclusions: Uncommon, potentially actionable EGFR mutations were found in 9% of plasma samples from East Asian NSCLC patients. In this clinical practice dataset, uncommon EGFR mutations were more prevalent than actionable biomarkers in other genes. These data support the use of NGS testing methods to identify NSCLC patients for appropriate EGFR-targeted therapy.

SHP2 Inhibition Benefits Epidermal Growth Factor Receptor mutated Non-Small Cell Lung Cancer Therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Leiming Xia ◽  
Lu Wen ◽  
Siying Wang
Keyword(s):  
Stem Cells ◽  
Synergistic Effects ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Combination Strategies ◽  
Lung Cancer Therapy ◽  
Src Homology ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tkis

: EGFR-TKIs are facing a big challenge of everlasting activated EGFR mutations which lack of effective binding sites, this barrier confers the dark sides that largely limited the outcome of NSCLC patients in clinic. Combination strategies show impressive anti-tumor efficacy comparing with EGFR-TKI mono-treatment, especially targeting both stem cells and non-stem cells. SHP2 (Src homology 2-containing phosphotyrosine phosphatase 2) plays an important role in regulating various malignant biology through hyper-activating intracellular pathways due to either over expression or catalytical mutation. Some pathways that SHP2 involved in were overlaps with EGFR downstream, and others were not subject to EGFR. Interestingly, SHP2 suppression was reported that can destroy the stemness of cancer. Therefore, we hypothesize SHP2 inhibitor might be an promising drug that could synergistically enhance or sensitize the anti-tumor efficacy of EGFR-TKIs in EGFR mutated NSCLC patients. Here, we summarized the mechanisms of SHP2 in regulating EGFR mutated NSCLC patients, attempted to reveal the potential synergistic effects of SHP2 inhibitor combined with EGFR-TKIs.

scholarly journals Detection of EGFR Activating and Resistance Mutations by Droplet Digital PCR in Sputum of EGFR-Mutated NSCLC Patients

2021 ◽  
Vol 15 ◽  
pp. 117955492199307
Author(s):  
Klaus Hackner ◽  
Anna Buder ◽  
Maximilian J Hochmair ◽  
Matthaeus Strieder ◽  
Christina Grech ◽  
...  
Keyword(s):  
Stable Disease ◽  
Progressive Disease ◽  
Kinase Inhibitor ◽  
Diagnostic Yield ◽  
Resistance Mutation ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
Percent Agreement ◽  
Nsclc Patients ◽  
Egfr Mutated

Background: Proof of the T790M resistance mutation is mandatory if patients with EGFR-mutated non-small cell lung cancer (NSCLC) progress under first- or second-generation tyrosine kinase inhibitor therapy. In addition to rebiopsy, analysis of plasma circulating tumor DNA is used to detect T790M resistance mutation. We studied whether sputum is another feasible specimen for detection of EGFR mutations. Methods: Twenty-eight patients with advanced EGFR-mutated NSCLC were included during stable and/or progressive disease. The initial activating EGFR mutations (exon 19 deletions or L858R mutations) at stable disease and at progressive disease (together with T790M) were assessed in simultaneously collected plasma and sputum samples and detected by droplet digital polymerase chain reaction (ddPCR). Results: Activating EGFR mutations were detected in 47% of the plasma samples and 41% of sputum samples during stable disease, and in 57% of plasma samples and 64% of sputum samples during progressive disease. T790M was detected in 44% of the plasma samples and 66% of the sputum samples at progressive disease. In ddPCR T790M-negative results for both specimens (plasma and sputum), negativity was confirmed by rebiopsy in 5 samples. Concordance rate of plasma and sputum for T790M was 0.86, with a positive percent agreement of 1.0 and a negative percent agreement of 0.80. Conclusions: We demonstrated that EGFR mutation analysis with ddPCR is feasible in sputum samples. Combination of plasma and sputum analyses for detection of T790M in NSCLC patients with progressive disease increases the diagnostic yield compared with molecular plasma analysis alone.

EGFR mutations in African American NSCLC patients occurs at a similar frequency to Caucasians but demonstrates an extreme bias to exon 19 mutations

2010 ◽  
Author(s):  
Govindaraja Atikukke ◽  
Michele L. Cote ◽  
Ann G. Schwartz ◽  
Gadgeel Shirish ◽  
Ayman O. Soubani ◽  
...  
Keyword(s):  
African American ◽  
Egfr Mutations ◽  
Similar Frequency ◽  
Nsclc Patients ◽  
Exon 19

Novel mutations and mutation pattern of epidermal growth factor receptor (EGFR) gene in Chinese patients with primary lung adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7667-7667
Author(s):  
T. Mok ◽  
P. Lui ◽  
K. C. Lam ◽  
A. Yim ◽  
I. Wan ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Egfr Mutation ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Novel Mutations ◽  
Egfr Gene ◽  
Mutation Pattern ◽  
Exon 20 ◽  
Egfr Tki ◽  
Exon 19

7667 Background: EGFR mutation is a diverse and complex phenomenon. Shigematsu et al (JNCI 97:339,2005), analyzing NSCLC samples from multiple ethnicities and histologic cell types, reported 11 types of in-frame deletions in exon 19 (46%), 9 missense mutation in exons 18, 20, 21 (45%) and 8 in-frame insertion in exons 20 (9%). 3/130 tumors (2.3%) had multiple mutations. Here we report the incidence, mutation pattern and novel finding of EGFR mutation in a homogenous ethnic group with adenocarcinoma of lung. Methods: Between 2004 and 2006 we isolated genomic DNA from 194 (archival 53, prospective 141) primary lung adenocarinoma for PCR amplification of EGFR exon 18–21. We isolated tumor cell by micro-dissection. PCR products were purified and sequenced using the BigDye Terminator Cycly Sequencing Ready Reaction Kit (Applied Biosystem) and run on Applied Biosystem 3100 Genetic Analyzer. Results: We found 79 EGFR mutations in 73 tumors (37.6%). Six (8.2%) had double mutations. IN-FRAME DEL: 10 types in exon 19 (39 cases, 49.4%); 1 type in exon 18 (1 case). MISSENSE MUTATION: 2 types in exon 18 (2 cases); 4 types in exon 20 (5 cases) and 2 types in exon 21 (29 cases, 36.7%) IN-FRAME INSERTION: 3 types in exon 20 (3 cases). Typical exon 19 E746-A750del and exon 21 L858R mutations accounted for 31% and 34%, respectively. We found 11 types of mutations not previously described.( Table ) Four pts with novel mutations received EGFR TKI and 3 attained PR (all with exon 19 del). Two pts have T790M mutations without prior exposure to EGFR TKI and both with double mutations. Conclusion: Mutation pattern of EGFR gene in Chinese pts with adenocarcinoma is similar to the Shigematsu report. The overall incidence of EGFR mutation and multiple mutations are higher but in-frame insertion in exon 20 is less common. Majority of the novel mutations are rare mutations involving exon 18 and 20. No significant financial relationships to disclose. [Table: see text]

Molecular changes in epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) biopsies at time of progression compared to initial biopsy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22066-e22066
Author(s):  
G. Speranza ◽  
V. Cohen ◽  
J. S. Agulnik ◽  
G. Chong ◽  
F. Meilleur ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Kinase Inhibitors ◽  
Genetic Alterations ◽  
Egfr Mutations ◽  
Missense Mutations ◽  
Molecular Changes ◽  
Mutational Status ◽  
Exon 19 Deletion ◽  
Exon 19

e22066 Background: EGFR mutations predict sensitivity and clinical outcome to tyrosine kinase inhibitors (TKI) in NSCLC. The two most commonly described mutations are Exon 19 deletion and Exon 21 L858R missense mutations. Genetic alterations over time have been described in other tumour types, but studies assessing EGFR genotypic changes with lung cancer progression are lacking. We sought to compare EGFR mutational status from lung tumors at time of recurrence or progression with the primary tumor. Methods: Using the Jewish General Hospital lung cancer database, of all patients diagnosed with NSCLC since 1999, those with biopsies at two different points in time were identified. All tumour samples were genotyped for EGFR exons 19 and 21 mutations using denaturing high performance liquid chromatography (dHPLC). Results: 29 patients were identified. Data for 12 patients, whose time of recurrence or progression varied between 4 months and 6 years, are available at this time. Of 12 patients, one had EGFR exon 19 mutation at time of diagnosis. One patient who initially displayed no EGFR mutation was found to have an exon 19 deletion at time of recurrence. The one with exon 19 at time of initial diagnosis continued to express exon 19 in the second biopsy. Conclusions: To our knowledge, this is the only study assessing changes in molecular genotype using dHPLC between primary and recurrent or progressive lung cancer biopsy specimens. Although sample size is small, it is evident that changes in EGFR mutational status can occur. Further prospective studies are required to determine how commonly molecular changes occur. No significant financial relationships to disclose.

Epidemiology of PD-L1 and ALK expression and EGFR mutational status in Argentinian patients with lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20565-e20565 ◽  
Author(s):  
Ruben Salanova ◽  
Julio C Calderazzo Pereyra ◽  
Laura Leguina ◽  
Asuncion Bena ◽  
Mariana Barberis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Mutational Status ◽  
Alk Positive ◽  
Egfr Mutant ◽  
Exon 19

e20565 Background: Until now, the results of the correlation between PD-L1, ALK expression and EGFR mutations remain controversial. We prospectively evaluated patterns among EGFR mutant, ALK positive and PD-L1 positive lung cancer patients. Methods: PD-L1 and ALK expression was evaluated in 342 adenocarcinomas (AD) of the lung using inmunohistochemestry (anti-PD-L1 22C3, anti-ALK D5F3), and EGFR mutations using real time PCR (therascreen EGFR RGQ PCR Kit version 2). PD-L1 was also evaluated in 36 squamous (SQ) cell carcinomas. Results: 181 of 342 patients with AD were positive for PD-L1. 108 were positive with a TPS value between 1 and 49, and 73 were positive with a TPS value higher than 50 (p = 0.002). 25 of 36 patients with SQ were positive for PD-L1. 17 were positive with a TPS value between 1 and 49, and 8 were positive with a TPS value higher than 50. 133 samples with AD PD-L1 positive and 97 PD-L1 negative were tested for EGFR and ALK, 33 and 14 respectively were positive for EGFR mutations (p = 0.15), with 45% for exon 19 deletions (p = 0.003), 5 and 0 respectively were positive for ALK translocations (p = 0.053). 210 of 342 patients were men and 132 were women, 117 and 64 were positive for PD-L1 expression respectively (p > 0.1). Conclusions: NSCLC with EGFR mutation showed a trend for higher frequency of positive PD-L1 expression and NSCLC harboring ALK rearrangement was significantly associated with PD-L1 expression. These findings might contribute to the understanding of the regulation of PD-L1 expression in lung cancer and its relation to ALK expression and EGFR mutation.

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