EGFR mutations and the correlation with gefitinib therapy in Chinese NSCLC—A systematic review based on individual patient data from 5 medical centers in China

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7187-7187 ◽  
Author(s):  
Y. Wu ◽  
W. Zhong ◽  
L. Li ◽  
L. Zhang ◽  
C. Zhou ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Egfr Mutation ◽  
Meta Analysis ◽  
Univariate Analysis ◽  
Correlation Factor ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Medical Centers ◽  
Nsclc Patients ◽  
Wild Group

7187 Background: EGFR mutations were found to have a significant association with response to gefitinib. To date, information on status of EGFR mutation in Chinese remains scanty. Comprehensive review of existing information on EGFR mutations is essential for treatment selection in Chinese patients with advanced NSCLC. Methods: We published 4 abstracts on EGFR mutation in Chinese patients at the 41st ASCO. We performed an IPD-meta-analysis on the data from the above investigators plus another one. The original individual EGFR mutations (exon 18,19,21) data was collected. Gefitinib was given with 250 mg/d until disease progression. Results: Total 407 cases were into the IPD review. The patient characteristic was male: female = 258:149; adenocarcinoma: other = 259:148; smoker: nonsmoker =178:153. The EGFR mutation rate was 3.05% (124/407). For adeno subgroup the EGFR mutation rate was 42.5% (110/259), non- adeno was 9.5% (14/148). In female the EGFR mutation rate was 41.6% (62/149), male was 24.0% (62/258). Non-smoker was 39.2% (60/153), smoker was 18.5% (33/178). In univariate analysis adeno, smoking, gender was significant predictive factors for EGFR mutation but in logistic regression only adeno is independent correlation factor (p = 0.000, 95% CI 2.078—9.001). Conclusions: The EGFR mutation is more common in no-smoking female adeno patients with NSCLC. The EGFR mutation group has a tendency of response rate to gefitinib compare to the EGFR wild group in NSCLC patients. [Table: see text] No significant financial relationships to disclose.

Exploring the applicability of immunotherapy in different EGFR mutation subgroups based on data analysis of 9,659 Chinese patients with NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21020-e21020
Author(s):  
Hao Peng ◽  
Hushan Zhang ◽  
Libin Zhang ◽  
Yang Wang ◽  
Xudong Shen ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Egfr Mutation ◽  
Clinical Laboratory ◽  
Checkpoint Inhibitors ◽  
White Blood Cells ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Wild Type ◽  
Tissue Samples ◽  
Nsclc Patients

e21020 Background: Here we assessed TMB level, PD-L1 expression, and their correlation in 9649 Chinese NSCLC patients with or without EGFR mutation, and different subtypes of EGFR mutations, to find out the underlying mechanisms that different outcomes of ICI for EGFR wild type and EGFR mutation NSCLC patients, and the possibility of ICI therapy for NSCLC patients of different EGFR mutation subtypes. Methods: Tumor tissue samples of 9649 NSCLC patients were collected from Janary 2018, expression of PD-L1 were detected by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. Gene mutation was detected by means of next generation sequencing (NGS). Performed Whole-Exome Sequencing (WES) on 70 tissue samples and corresponding White Blood Cells (WBCs) as matched control. Other samples were detected with panel covering whole exon regions of 733 cancer related genes. All these detections were performed in a College of American Pathologists (CAP)-certified and Clinical Laboratory Improvement Amendments (CLIA)-accredited lab for gene mutation analysis (3D Medicines Inc.,Shanghai, China). Statistical analysis was performed using GraphPad Prism (version 7.01) and SPSS version 21.0 (SPSS,Inc.). Results: Results showed that the proportion of EGFR mutation in Chinese patients with NSCLC was 51.3%, and the proportion of EGFR mutation subtypes were 42.6% L858R, 39.5% exon 19del, 2.3% exon 20in, 4.3% T790M. These samples were divided into different groups according to EGFR mutation, both WES based and panel-based results showed that EGFR wild type group displayed higher TMB level than EGFR mutation group (P < 0.05). However, except for exon 19del, L858R, exon 20in, no significant differences were found between wild type and other EGFR mutation subtypes. Furthermore, results of IHC revealed that, higher proportion of strong positive PD-L1 expression (TPS≥50) were found in EGFR wild type than exon 19del, L858R and exon 20in, no significant correlation was found between TMB level and PD-L1 expression. Conclusions: EGFR mutations account for half of Chinese NSCLC patients. The biomarkers of immune checkpoint inhibitors (such as TMB and PD-L1) are different in various EGFR mutation subtypes, which may indicate that for some NSCLC patients with EGFR mutation subtypes, they may also respond to ICI treatment as wild-type.

HSR19-082: Epidemiological Findings and Outcomes in Non-Small Cell Lung Cancer Patients with Exon 20 Insertion Mutations: A Meta-Analysis

2019 ◽  
Vol 17 (3.5) ◽  
pp. HSR19-082
Author(s):  
Victoria Crossland ◽  
Aaron Galaznik ◽  
Huamao M. Lin ◽  
Dimitrios Tomaras ◽  
Shan Ashton Garib ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Meta Analysis ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20 ◽  
Meta Analyses ◽  
Nsclc Patients ◽  
Insertion Mutations

Background: Epidermal growth factor receptor (EGFR) mutations are frequently found in non-small cell lung cancer (NSCLC) patients. Various EGFR mutations respond differently to EGFR tyrosine kinase inhibitors (TKIs), and several TKIs have been approved for use on common mutations but none have been approved for EGFR exon 20 insertions, indicating a need for targeted therapy for this subpopulation. A systematic literature review (SLR) and meta-analysis were conducted to synthesize epidemiological and outcome data for the uncommon EGFR exon 20 insertion mutation. Methods: An SLR was performed on August 7, 2018 following the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using the Population, Intervention Comparators, Outcomes and Study Design (PICOS) criteria. Studies were identified based on a systematic search using key biomedical literature databases: EMBASE, MEDLINE, and Cochrane. Relevant congress abstracts published between 2015–2018 were also identified. Two independent reviewers screened all citations and full-text articles using PICOS-based criteria; any discrepancies were resolved by a third independent reviewer. Data were extracted into a predefined template for meta-analysis and summarized using the PRISMA flow diagram. Results: A total of 61 studies reporting the number of EGFR mutation−positive patients and/or NSCLC patients were identified. A meta-analysis found that 3.7% of EGFR mutation−positive patients and 0.8% of NSCLC patients harbored the EGFR exon 20 insertion, with geographic variations in epidemiology. There were 12, 10, and 12 studies, respectively, that reported overall survival, progression-free survival, and overall response rates in 2 cohorts, patients with EGFR exon 20 insertions and patients without EGFR exon 20 mutations. A Most patient populations in these studies included a mixture of treatment at various lines. A meta-analysis of outcomes across these studies showed that patients with EGFR exon 20 insertions experienced worse outcomes compared with those without the mutation (Table 1). Meta-analyses were weighted based on each study’s relevant population. No economic or quality of life studies were identified. Conclusions: Exon 20 insertion mutations represent an important subgroup of EGFR mutations in patients with NSCLC, and current therapies have limited efficacy. These relatively poor outcomes indicate a need for novel treatment strategies.

scholarly journals Tissue or blood: which is more suitable for detection of EGFR mutations in non-small cell lung cancer?

2018 ◽  
Vol 33 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Rong Biaoxue ◽  
Yang Shuanying
Keyword(s):  
Lung Cancer ◽  
Receiver Operating Characteristic Curve ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Egfr Mutation ◽  
Meta Analysis ◽  
Characteristic Curve ◽  
Egfr Mutations ◽  
Mutation Status ◽  
Operating Characteristic Curve

Background: Many studies have evaluated the accuracy of EGFR mutation status in blood against that in tumor tissues as the reference. We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations. Methods: Investigations that provided data on EGFR mutation status in blood were searched in the databases of Medline, Embase, Ovid Technologies and Web of Science. The detect efficiency of EGFR mutations in paired blood and tissues was compared using a random-effects model of meta-analysis. Pooled sensitivity and specificity and diagnostic accuracy were calculated by receiver operating characteristic curve. Results: A total of 19 studies with 2,922 individuals were involved in this meta-analysis. The pooled results showed the positive detection rate of EGFR mutations in lung cancer tissues was remarkably higher than that of paired blood samples (odds ratio [OR] = 1.47, p<0.001). The pooled sensitivity and specificity of blood were 0.65 and 0.91, respectively, and the area under the receiver operating characteristic curve was 0.89. Conclusions: Although blood had a better specificity for detecting EGFR mutations, the absence of blood positivity should not necessarily be construed as confirmed negativity. Patients with negative results for blood should decidedly undergo further biopsies to ascertain EGFR mutations.

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]

EGFR mutation analysis from REASON: A registry for the epidemiologic and scientific evaluation of EGFR mutation status in newly diagnosed NSCLC patients stage IIIB/IV.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18016-e18016 ◽  
Author(s):  
Wolfgang Schuette ◽  
Wilfried Ernst Erich Eberhardt ◽  
J.-Mathias Graf von der Schulenburg ◽  
Manfred Dietel ◽  
Peter Schirmacher ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Smoking Status ◽  
Epidemiological Data ◽  
Standard Test ◽  
Test Method ◽  
Stage Iiib ◽  
Egfr Mutations ◽  
Newly Diagnosed ◽  
Never Smokers ◽  
Nsclc Patients

e18016^ Background: Somatic mutations in the EGFR gene predict for sensitivity to EGFR TKI in patients with adv. NSCLC, yet limited data exists on EGFR mutation rates of all 4 exons in all NSCLC histologies. Methods: The REASON study (NCT00997230) aims to generate data on EGFR mutation (M) status, association of EGFR-M status with clinico-pathological parameters, treatment decisions and clinical outcomes for EGFR M+ patients from a large sample of stage IIIB/IV NSCLC patients in Germany. 4279 subjects for whom EGFR M testing was planned were enrolled at 151 sites (85% hospital based) in Germany. Standard test method was Sanger sequencing. While analysis of exons 19 and 21 was obligatory, exons 18 and 20 were not routinely done at all labs. Primary objectives are epidemiological data on EGFR M status and correlation with clinico-pathological features. Secondary aims are clinical outcome of all EGFR M+ patients (PFS, OS, DCR), clinical management and pharmaco-economic data associated with diagnosis and treatment of EGFR M+ patients. Results: A 2nd interim analysis provided baseline data on 3973 patients. 63% were male; 82% ever-smokers, 18% never-smokers. Adenocarcinoma is most frequent (69%), followed by squamous epithelial carcinoma (19%). 379 patients had EGFR mutations (9.9%) with 9.5% predicting TKI sensitivity and 0.4% resistance. Most common were exon 19 deletions (50%; with 35% DelE746-A750) followed by exon 21 mutations (36.8%; with 72% L858R). Multivariate analysis revealed association of gender, smoking status and histological subtype with EGFR M status (Table). 50% of M+ patients received 1st line TKI vs. 48% doublet CTX. Conclusions: REASON provides the largest data base yet on EGFR M status in Caucasian patients with newly diagnosed stage IIIB/IV NSCLC. Smoking followed by adeno-carcinoma was the strongest predictive factor for EGFR M. Only 50% of EGFR M+ patients received 1st line TKI. [Table: see text]

EGFR variant III expression in Chinese patients with non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18022-e18022
Author(s):  
Jie Wang ◽  
Jianchun Duan ◽  
Hua Bai ◽  
Lu Yang ◽  
Tongtong An ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Statistical Significance ◽  
Chinese Patients ◽  
Mrna Levels ◽  
Clinicopathologic Characteristics ◽  
Cell Lung Carcinoma ◽  
Post Surgery ◽  
Former Smokers ◽  
Nsclc Patients ◽  
Egfr Tki

e18022 Background: Patients with advanced squamous cell lung carcinoma (SCC), even though harboring the EGFR mutation, showed an inferior response to EGFR-TKI. The aim of this retrospective study was to determine the clinicopathologic characteristics and distribution profiles of EGFRv III in Chinese NSCLC patients, and to explore the likely relationship between EGFRv III mRNA levels and the response to EGFR-TKI. Methods: Frozen tissues were retrospectively obtained from 114 NSCLC patients who received surgery resection and 13 advanced NSCLC patients who received EGFR-TKI treatment in Peking Universuty Cancer Hospital. EGFRv III expression was detected by RT-PCR and EGFR mutation was detected by denaturing high-performance liquid chromatography (DHPLC). The association between EGFRv III and clinicopathologic features was investigated by statistical analysis. Results: frequency of EGFRv III in 114 post-surgery NSCLC patients was 7.02% (8/114), including 11.11% (6/54) in SCC and 3.64% (2/55) in adenocarcinomas (ADC). The frequency of EGFRv III expression was higher in SCC than in ADC, but the difference didn’t reach statistical significance (p = 0.269). In the subgroup of 8 EGFRv III-positive patients, 7 (87.5%) were male, 6 patients (75.0%) were smokers or former smokers,. No EGFR mutation was detected. In 13 advanced SCC patients who received treatment with EGFR-TKI, no patient harboring EGFRv III was found, and 3 patients (23.08%) were tested for EGFR mutation. Conclusions: The frequency of EGFRv III in Chinese NSCLC was low and squamous histology, smokers or former- smokers, and male gender might be related to EGFRv III and have effects exclusive of EGFR mutation.

A meta-analysis of comparing EGFR-TKI with chemotherapy as the second-line treatment of NSCLC patients with wild-type EGFR.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19166-e19166 ◽  
Author(s):  
Guanghui Gao ◽  
Shengxiang Ren ◽  
Aiwu Li ◽  
Yayi He ◽  
Xiaoxia Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Overall Response ◽  
Nsclc Patients ◽  
Egfr Tki

e19166 Background: The efficacy of comparing the EGFR-TKI with standard chemotherapy in the second-line treatment of advanced NSCLC with wide-type EGFR were still controversial. To derive a more precise estimation of the two regimens, a meta-analysis was performed. Methods: Medical databases and conference proceedings were searched for randomized controlled trials which compared EGFR-TKI (gefitinib or erlotinib) with standard second-line chemotherapy (docetaxel or pemetrexed) in patients with NSCLC. Endpoints were overall survival, progression-free survival and overall response. Results: Three eligible trials (INTEREST, TITAN and TAILOR) were identified. Lacking for data of overall survival of TAILOR trial, So we only make a preliminary meta-analysis for overall survival. The intention to treatment (ITT) analysis demonstrated that the patients receiving EGFR-TKI had a significantly shorter progression-free survival (PFS) than patients treated with chemotherapy (hazard ratio (HR) = 1.31; 95% confidence intervals (CI) = 1.10-1.56; P = 0.002). The overall survival (OS) and overall response rate (ORR) were coparable between this two groups (HR = 0.96; 95%CI = 0.77-1.19; P = 0.69; relative risk (RR) = 0.37; 95%CI = 0.09-1.54; P = 0.17). Conclusions: Although chemotherapy had a clear superiority in PFS as second-line treatment for patients without EGFR mutations compared with EGFR-TKI, OS and ORR were equal in this two regimens. The toxicity profiles might play an important role in the decision to choose EGFR-TKI or chemotherapy. These findings still need to be verified in larger confirmatory studies in future.

Assessment of EGFR mutation status in matched plasma and tumor tissue of NSCLC patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20032-e20032
Author(s):  
Qin Feng
Keyword(s):  
Tumor Tissue ◽  
Egfr Mutation ◽  
Circulating Tumor Dna ◽  
Egfr Mutations ◽  
Amplification Refractory Mutation System ◽  
Circulating Dna ◽  
Mutation Status ◽  
Nsclc Patients ◽  
Tumor Dna ◽  
Egfr Tkis

e20032 Background: Tumor tissue is currently used for EGFR testing non-small cell lung cancer (NSCLC) patients, but the detection of circulating tumor DNA (ctDNA) is being actively investigated as a new method for the detection and longitudinal monitoring of actionable mutations in plasma samples. Around 30% patients with EGFR mutation presented inconsistent status of EGFR mutation between in tissues and plasma. We compared EGFR mutation detection in circulating tumor DNA from blood to that in matched tissue. Methods: EGFR mutation status were assessed by the Human EGFR Gene Mutations Detection Kit (Beijing ACCB Biotech Ltd.) both in tissue and plasma. Retrospective analysis to evaluate the concordance of tissue and plasma EGFR determination for assessing eligibility for EGFR-TKIs therapy in NSCLC patients. 10 mL tubes of blood were collected from patients who never had been treated by EGFR TKI, and plasma circulating tumor DNA were extracted from plasma by Biomark Circulating DNA Kit. Qubit2.0 Fluorometer was used to make plasma circulating DNA tumor quantitation. The concentration of final DNA sample is ≦2ng/μl. Results: A total of 224 NSCLC patients were detected by Amplification Refractory Mutation System (ARMS), with 92 tissue positive and 49 blood positive. Results showed 53.3% sensitivity in overall samples, but 81.4% sensitivity in ⅢB~Ⅲ patients. The specificity is 100%. Conclusions: The high sensitivity and specificity between tissue and plasma EGFR determination supports the blood-based EGFR mutation testing to determinate the eligibility of NSCLC patients for EGFR-TKIs treatment, especialy in ⅢB~Ⅲ NSCLC patients. Blood, in particular plasma, is a good screening substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC. EGFR mutation positivity in blood could be used to recommend EGFR TKIs treatment, but the blood negativity should be confirmed with other sample, biopsy tissue, pleural effusion, etc..

Chemoimmunotherapy combination: Potential option for metastatic NSCLC patients with EGFR mutation resistant to osimertinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20618-e20618
Author(s):  
Bo Yang ◽  
Yaping Long ◽  
Yi Hu
Keyword(s):  
Egfr Mutation ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Combination Group ◽  
Metastatic Nsclc ◽  
Number Of Patients ◽  
Grade 3 ◽  
Egfr Mutant ◽  
Nsclc Patients

e20618 Background: Osimertinib has been emerged as the standard selection in EGFR T790M-positive NSCLC patients who failed prior treatment with EGFR TKIs. However, acquired resistance to osimertinib is a growing clinical challenge. Despite the significant antitumor activity of Chemoimmunotherapy (CIT) combinations in NSCLC, clinical benefit in patients with EGFR mutations has not been shown obviously. Our objective was to assess the effectiveness and tolerability of CIT for metastatic EGFR-mutant NSCLC patients with acquired resistance to Osimertinib. Methods: We conducted a retrospective study in patients with sensitizing EGFR-mutant NSCLC who were resistant to Osimertinib and received anti-PD1 immunotherapy combined with chemotherapy at Chinese PLA General Hospital. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and toxicities were examined. Results: Between Oct 2015 and Nov 2018, 11 patients were available for analysis, 45.5% male, 45.5% ECOG PS 0-1, median age 54 years, all pts who failed treatment with Osimertinib had received previously targeted therapies. In this CIT combination group, 6 [54.5%] of 11 pts received pembrolizumab and 5[54.5%] of 11 pts received Nivolumab anti-PD1 therapy, 8 [72.7%] of 11 pts received mono-chemotherapy and 3 [27.3%] of 11 pts received platinum-based doublet chemotherapy. The median PFS was 7.47 months (95% CI 3.04 to 11.89). Despite Median OS was not reached, the OS rate at one year was 6 [54.5%] of 11. The ORR was 5 [45.5%] of 11. Treatment-related adverse events (TRAE) of grade 3 or higher were reported in 6 [54.5%] of 11 patients. The most common grade 3 or worse TRAEs were fatigue (3 [27.3%] of 11) and anemia (3 [27.3%] of 11); The following ≥Grade 3 TRAEs occurred once: decreased neutrophil count, acute kidney injury, gastrointestinal bleeding. One patient discontinued treatment because of immune-associated gastroenteritis. Conclusions: In metastatic NSCLC patients with activating EGFR mutation resistant to Osimertinib, our single institution real-world experience in Chemoimmunotherapy combination shows promising activity and acceptable toxicity profile. Given the small number of patients studied, further clinical trials are warranted.

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