scholarly journals Effect of β-Blocker in Treatment-Naïve Patients With Advanced Lung Adenocarcinoma Receiving First-Generation EGFR-TKIs

2020 ◽  
Vol 10 ◽  
Author(s):  
Chia-Hao Chang ◽  
Chih-Hsin Lee ◽  
Jen-Chung Ko ◽  
Lih-Yu Chang ◽  
Ming-Chia Lee ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
First Generation ◽  
Treatment Naïve ◽  
Β Blocker ◽  
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

Mutation and treatment profiles of patients with concurrent EGFR and ALK actionable mutations (muts).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3138-3138
Author(s):  
Jun Zhao ◽  
Caixia Liu ◽  
Hui Liu ◽  
Yong He ◽  
Liqiang Rao ◽  
...  
Keyword(s):  
First Generation ◽  
Low Frequency ◽  
Resistance Mechanisms ◽  
The Other ◽  
Kaplan Meier ◽  
Tki Resistance ◽  
Treatment Naïve ◽  
Alk Positive ◽  
Egfr Tki ◽  
Egfr Tkis

3138 Background: Actionable muts in EGFR and ALK define two molecular subtypes sensitive to EGFR-TKIs and ALK-TKIs, respectively. Although generally mutually exclusive, they did co-exist in some cases. However, when and how do they co-exist are not well understood. Methods: Pts with concurrent actionable muts in ALK and EGFR were selected from our database. Their mutation profiles and treatment histories were analyzed. PFS was estimated using Kaplan-Meier method. Results: Among 341 ALK-positive ( ALK-pos) and 3804 EGFR-positive ( EGFR-pos) pts, 9 (2.6% of ALK-pos, 0.2% of EGFR-pos) had concurrent EGFR and ALK actionable muts, including 3 EX19Indel + EML4-ALK, 2 EX19Indel + STRN-ALK, 2 L858R + L1152R, 1 L858R + EML4-ALK, and 1 G719C + S768I + STRN-ALK. All 9 pts had lung cancer. One pt with EX19Indel + EML4-ALK was treatment naïve. The other 8 pts have taken ≥ 1 EGFR-TKIs. The mPFS of these pts on first-generation EGFR-TKIs was 22 mo (95% CI: 11 - NR). Except for 1 pt who progressed on Gefitinib and subsequently on Osimertinib had a T790M+C797G, the other 7 EGFR-TKI resistance pts had no common known resistance muts. 3 pts ordered NGS tests before taking EGFR-TKIs. None of them had ALK muts at that time. Later, 1 pt (19Indel) gained an STRN-ALK after 15 mo on Osimertinib, 1 pt (L858R) gained an EML4-ALK after 5 mo on Gefitinib, and 1 pt (L858R) gained an L1152R after 10 mo on Afatinib. Therefore, ALK muts were likely developed as resistance mechanisms during EGFR-TKIs therapies in these 3 pts. Unfortunately, with no information on ALK status before EGFR-TKI therapies, we can not tell if the ALK muts were also developed during and conferred resistance to EGFR-TKI therapies in the other 5 pts. Both STRN-ALK and ALK L1152R were recorded 4 times in our database, and they concurred with EGFR actionable muts in 3 and 2 of the 4 records, respectively. Conclusions: ALK and EGFR actionable muts concurred at a relatively low frequency in our pts. In some cases, ALK muts were developed during EGFR-TKI therapies. Developed either together or sequentially, some combinations of EGFR and ALK muts, such as L858R with L1152R and EX19Indel with ALK fusion, may form more easily or may be preferable than other combinations for the development or evoluation of tumors.

scholarly journals Efficacy of EGFR-TKI Plus Chemotherapy or Monotherapy as First-Line Treatment for Advanced EGFR-Mutant Lung Adenocarcinoma Patients With Co-Mutations

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhengyu Yang ◽  
Ya Chen ◽  
Yanan Wang ◽  
Shuyuan Wang ◽  
Minjuan Hu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
First Generation ◽  
Progression Free Survival ◽  
Poor Response ◽  
Time To Progression ◽  
Free Survival ◽  
Egfr Mutant ◽  
Egfr Tki ◽  
Generation Sequencing ◽  
Egfr Tkis

BackgroundCo-mutations was associated with poor response to EGFR-TKIs. First-generation EGFR-TKIs combined with chemotherapy was reported to be more effective than TKIs alone in advanced lung adenocarcinoma patients.ObjectiveThis retrospective study aimed to explore whether EGFR-mutant patients with co-mutations can benefit from EGFR-TKIs plus chemotherapy.Patients and MethodsWe retrospectively collected data of 137 EGFR-mutant patients with advanced lung adenocarcinoma who underwent next-generation sequencing in our hospital in 2018. Among them, 96 were treated with EGFR–TKIs alone and 41 received EGFR–TKIs plus chemotherapy. We analyzed the progression-free survival (PFS) of patients with co-mutations using different treatments.ResultsConcurrent TP53 mutations, especially exon 4 and 6, were associated with a markedly shorter time to progression on EGFR-TKI monotherapy (11.4 months vs. 16.6 months, P=0.003), while EGFR–TKIs plus chemotherapy would benefit those patients more (with TP53: 11.4 months vs. 19.1 months, P=0.001, HR=0.407; without TP53: 16.6 months vs. 18.9 months, P=0.379, HR=0.706). The incidence of T790M after resistance was equal in patients treated with different treatments (53% vs. 53%, P=0.985).ConclusionsIn our study, concurrent TP53 mutations were found to be risk factors for EGFR-TKI monotherapy, but TKI combined with chemotherapy could eliminate this heterogeneity.

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.

scholarly journals P1.15-30 Survival of Patients with Advanced NSCLC Treated with First-Generation EGFR-TKIs at a Cancer Hospital in Thailand, 2011-2016

2018 ◽  
Vol 13 (10) ◽  
pp. S624-S625
Author(s):  
S. Sukauichai ◽  
C. Tovanabutra ◽  
S. Wanlikitkul ◽  
K. Chomprasert
Keyword(s):  
First Generation ◽  
Advanced Nsclc ◽  
Cancer Hospital ◽  
Egfr Tkis

scholarly journals High expression of hypoxia inducible factor 1α related with acquired resistant to EGFR tyrosine kinase inhibitors in NSCLC

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qian Jin ◽  
Feihua Huang ◽  
Xianrong Xu ◽  
Haidong He ◽  
Yingqing Zhang
Keyword(s):  
First Generation ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Hypoxia Inducible Factor ◽  
High Expression ◽  
Normal Lung ◽  
Nsclc Tissue ◽  
T790m Mutation ◽  
Level Group ◽  
Egfr Tkis

AbstractThe acquired resistance of the first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a main factor leading to poor prognosis of non-small cell lung cancer (NSCLC), so we researched whether the high expression of hypoxia-inducible factor-1α (HIF-1α) in EGFR-TKIs sensitive NSCLC tissue tends to induce the acquired resistance. We detected the HIF-1α in normal lung tissue, EGFR-TKIs sensitive NSCLC tissue, the first generation EGFR-TKIs acquired resistant NSCLC tissue and acquired EGFR T790M mutation NSCLC tissue with the method of immunohistochemistry. Then, we compared the expression of HIF-1α in these tissues, and evaluate the effect of HIF-1α expression to the occurrence of acquired resistance. The expression of HIF-1α was much higher in the EGFR-TKIs sensitive NSCLC tissue than that in normal lung tissue. HIF-1α level became higher after the occurrence acquired resistance. There was negative correlation between HIF-1α level before receiving treatment and the time of acquired resistance occurring as well as the acquired EGFR T790M mutation occurring. As the treatment going on, EGFR-TKIs sensitivity rate of low HIF-1α level group was much higher than that of high level group. The high expression of HIF-1α related with the acquired resistance of the first generation EGFR-TKIs, and HIF-1α can be a biomarker to predict the early occurrence of acquired resistance.

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