scholarly journals Podoplanin-Positive Cancer-Associated Fibroblasts in the Tumor Microenvironment Induce Primary Resistance to EGFR-TKIs in Lung Adenocarcinoma with EGFR Mutation

2014 ◽  
Vol 21 (3) ◽  
pp. 642-651 ◽  
Author(s):  
Tatsuya Yoshida ◽  
Genichiro Ishii ◽  
Koichi Goto ◽  
Shinya Neri ◽  
Hiroko Hashimoto ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Cancer Associated Fibroblasts ◽  
Primary Resistance ◽  
Egfr Tkis

High PD-L1 expression correlates with primary resistance to EGFR-TKIs in treatment naïve advanced EGFR-mutant lung adenocarcinoma patients

Lung Cancer ◽  
2019 ◽  
Vol 127 ◽  
pp. 37-43 ◽  
Author(s):  
Kuo-Hsuan Hsu ◽  
Yen-Hsiang Huang ◽  
Jeng-Sen Tseng ◽  
Kun-Chieh Chen ◽  
Wen-Hui Ku ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Primary Resistance ◽  
Treatment Naïve ◽  
Egfr Mutant ◽  
Egfr Tkis

Co-mutation features in treatment-naïve EGFR-mutant lung adenocarcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21616-e21616
Author(s):  
Jun Zhao ◽  
Zaiwen Fan ◽  
Donghong Chen ◽  
Minglei Zhuo ◽  
Zhen Liang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Chinese Patients ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Treatment Naïve ◽  
Exon 19 Deletion ◽  
Egfr Mutant ◽  
Egfr Tkis ◽  
Exon 19

e21616 Background: In Chinese patients with lung adenocarcinoma, the positive rate of EGFR mutation was 40% - 50%, EGFR-TKIs therapy for lung cancer was also aimed at this part of patients. However, different EGFR mutation types have different therapeutic effects, this study focuses on different EGFR mutation types to divide the population of lung adenocarcinoma. Methods: We retrospectively reviewed gene test results of two hundred and sixty-two treatment-naïve adenocarcinoma patients. Tumor tissues (199, 76%), plasma (46, 17.5%) and other samples (17, 6.5%) were subject to next-generation sequencing using a 59-gene panel, which enables simultaneously assess SNV, Indel, rearrangements and CNV variations. Results: There were 174 females. These patients were divided into four groups, which 139 were EGFR L858R, 99 were EGFR exon 19 deletion, 7 were EGFR 20 ins and 17 were uncommon EGFR mutations, the co-mutation proportions with EGFR were 84.9% (118/139), 76.8% (76/99), 71.4% (5/7) and 94.1% (16/17) respectively. The mean numbers of co-mutation genes in L858R and exon 19 deletion were 4.173 and 3.258 (p<0.05). TP53 mutation was detected in 14.3% (1/7) 20ins group, which had a significant difference to L858R (59.7%, 83/139) and uncommon mutation groups (70.6%, 12/17) (p<0.05). Meanwhile, EGFR amplification proportion in L858R (18%, 25/139) and exon 19 deletion (6.1%, 6/99) were significantly different (p<0.05). The actionable mutations associated with target therapy involved in multiple pathways, for example, the HRR pathway and cell cycle pathway, related genes had no significant difference among the four groups. In these lung adenocarcinoma patients, we also found 6 EGFR T790M (2.3%, 6/262). Three cases accompanied with exon 19 deletion, and another three were L858R, no distribution in 20ins and uncommon groups. Conclusions: The phenomenon of concurrent gene mutation in treatment-naïve EGFR-mutant lung adenocarcinoma is common. EGFR mutant subgroups have different co-mutation features, like gene number and mutated genes. It may be the factor leading to different therapeutic effects of EGFR-TKIs, and indicate the importance of multiplex molecular test and further researches of target therapies.

Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L

2016 ◽  
Vol 34 (27) ◽  
pp. 3248-3257 ◽  
Author(s):  
Yoshiko Urata ◽  
Nobuyuki Katakami ◽  
Satoshi Morita ◽  
Reiko Kaji ◽  
Hiroshige Yoshioka ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Performance Status ◽  
Phase Iii ◽  
Survival Times ◽  
Egfr Tyrosine Kinase ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Egfr Tkis

Purpose The epidermal growth factor receptor (EGFR) tyrosine kinase has been an important target for non–small-cell lung cancer. Several EGFR tyrosine kinase inhibitors (TKIs) are currently approved, and both gefitinib and erlotinib are the most well-known first-generation EGFR-TKIs. This randomized phase III study was conducted to investigate the difference between these two EGFR-TKIs. Patients and Methods Previously treated patients with lung adenocarcinoma were randomly assigned to receive gefitinib or erlotinib. This study aimed to investigate the noninferiority of gefitinib compared with erlotinib. The primary end point was progression-free survival (PFS). Results Five hundred sixty-one patients were randomly assigned, including 401 patients (71.7%) with EGFR mutation. All baseline factors (except performance status) were balanced between the arms. Median PFS and overall survival times for gefitinib and erlotinib were 6.5 and 7.5 months (hazard ratio [HR], 1.125; 95% CI, 0.940 to 1.347; P = .257) and 22.8 and 24.5 months (HR, 1.038; 95% CI, 0.833 to 1.294; P = .768), respectively. The response rates for gefitinib and erlotinib were 45.9% and 44.1%, respectively. Median PFS times in EGFR mutation–positive patients receiving gefitinib versus erlotinib were 8.3 and 10.0 months, respectively (HR, 1.093; 95% CI, 0.879 to 1.358; P = .424). The primary grade 3 or 4 toxicities were rash (2.2% for gefitinib v 18.1% for erlotinib) and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation (6.1%/13.0% for gefitinib v 2.2%/3.3% for erlotinib). Conclusion The study did not demonstrate noninferiority of gefitinib compared with erlotinib in terms of PFS in patients with lung adenocarcinoma according to the predefined criteria.

scholarly journals 1233P EGFR-TKIs compared with radiotherapy for patients of stage IV lung adenocarcinoma with EGFR mutation

2021 ◽  
Vol 32 ◽  
pp. S976
Author(s):  
Y. Wang ◽  
W. Yu ◽  
J. Shi ◽  
M. Qiu ◽  
N. Jiang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Stage Iv ◽  
Egfr Tkis

scholarly journals P48.10 Efficacy of EGFR-TKIs vs TKIs Plus Chemotherapy as First-Line Treatment in EGFR-Mutation Lung Adenocarcinoma With Liver Metastases

2021 ◽  
Vol 16 (10) ◽  
pp. S1110
Author(s):  
H. Wang ◽  
M. Li ◽  
R. Xing ◽  
C. Wei ◽  
Z. Ma
Keyword(s):  
Lung Adenocarcinoma ◽  
Liver Metastases ◽  
Egfr Mutation ◽  
Line Treatment ◽  
First Line ◽  
Egfr Tkis ◽  
First Line Treatment

scholarly journals A Case of Novel Inversion Mutation of EGFR Exon 19 Leading to Primary Resistance to EGFR TKIs in Lung Adenocarcinoma

2018 ◽  
Vol 13 (6) ◽  
pp. e97-e101
Author(s):  
Shaomei Li ◽  
Jiuzhou Zhao ◽  
Qiming Wang
Keyword(s):  
Lung Adenocarcinoma ◽  
Primary Resistance ◽  
Egfr Tkis ◽  
Exon 19

scholarly journals Combined treatment with metformin and gefitinib overcomes primary resistance to EGFR-TKIs with EGFR mutation via targeting IGF-1R signaling pathway

2018 ◽  
Vol Volume 12 ◽  
pp. 75-86 ◽  
Author(s):  
Yong-hong Pan ◽  
Lin Jiao ◽  
Cai-yu Lin ◽  
Cong-hua Lu ◽  
Li Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Egfr Mutation ◽  
Combined Treatment ◽  
Primary Resistance ◽  
Egfr Tkis

scholarly journals Cytoplasmic ERβ1 expression is associated with survival of patients with Stage IV lung adenocarcinoma and an EGFR mutation at exon�21 L858R subsequent to treatment with EGFR‑TKIs

2019 ◽  
Author(s):  
Cheng He ◽  
Yifu He ◽  
Huiqin Luo ◽  
Ming Zhang ◽  
Jing Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Stage Iv ◽  
Egfr Tkis

scholarly journals Predicting EGFR mutation status in lung adenocarcinoma presenting as ground-glass opacity: utilizing radiomics model in clinical translation

2021 ◽  
Author(s):  
Bo Cheng ◽  
Hongsheng Deng ◽  
Yi Zhao ◽  
Junfeng Xiong ◽  
Peng Liang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
External Validation ◽  
Discrimination Performance ◽  
Ground Glass Opacity ◽  
Gradient Boosting ◽  
Time Saving ◽  
Mutation Status ◽  
Clinical Model ◽  
Egfr Tkis

Objectives: This study aimed to establish a noninvasive radiomics model based on computed tomography (CT), with favorable sensitivity and specificity to predict EGFR mutation status in GGO-featured lung adenocarcinoma that subsequently guiding the administration of targeted therapy. Methods: Clinical-pathological information and preoperative CT-images of 636 lung adenocarcinoma patients (464, 100, and 72 in the training, internal, and external validation sets, respectively) that underwent GGO lesions resection were included. A total of 1476 radiomic features were extracted with gradient boosting decision tree (GBDT). Results: The established radiomics model containing 252 selected features showed an encouraging discrimination performance of EGFR mutation status (mutant or wild-type), and the predictive ability was superior to that of the clinical model (AUC: 0.901 vs. 0.674, 0.813 vs. 0.730, and 0.801 vs. 0.746 the training, internal, and external validation sets, respectively). The combined radiomics plus clinical model showed no additional benefit over the radiomics model in predicting EGFR status (AUC: 0.909 vs. 0.901, 0.803 vs. 0.813, 0.808 vs. 0.801, respectively, in three cohorts). Uniquely, this model was validated in a cohort of lung adenocarcinoma patients who undertaken adjuvant EGFR-TKIs and harbored unresected GGOs, leading to a significantly improved potency of EGFR-TKIs (response rate: 33.9% vs. 62.5%, P =0.04; before- and after-prediction, respectively). Conclusion: This presented radiomics model can be served as a noninvasive and time-saving approach for predicting the EGFR mutation status in lung adenocarcinoma presenting as GGO.

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