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Egfr-tki treatment for lung cancer

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https://www.readbyqxmd.com/read/28734822/icotinib-versus-whole-brain-irradiation-in-patients-with-egfr-mutant-non-small-cell-lung-cancer-and-multiple-brain-metastases-brain-a-multicentre-phase-3-open-label-parallel-randomised-controlled-trial
#1
Jin-Ji Yang, Caicun Zhou, Yisheng Huang, Jifeng Feng, Sun Lu, Yong Song, Cheng Huang, Gang Wu, Li Zhang, Ying Cheng, Chengping Hu, Gongyan Chen, Li Zhang, Xiaoqing Liu, Hong Hong Yan, Fen Lai Tan, Wenzhao Zhong, Yi-Long Wu
BACKGROUND: For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. METHODS: We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China...
July 19, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28730963/increased-expression-of-ire1%C3%AE-associates-with-the-resistant-mechanism-of-osimertinib-azd9291-resistant-non-small-cell-lung-cancer-hcc827-osir-cells
#2
Zheng-Hai Tang, Min-Xia Su, Xia Guo, Xiao-Ming Jiang, Lin Jia, Xiuping Chen, Jin-Jian Lu
BACKGROUND: Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients. OBJECTIVE: Establishment of the OSI-resistant HCC827/OSIR cell line and study of its resistant mechanism. METHOD: The anti-proliferative effect was studied through MTT and colony formation assays. The protein expression was detected by Western blot assay...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28719349/identification-of-g2607a-mutation-in-egfr-gene-with-a-significative-rate-in-moroccan-patients-with-bladder-cancer
#3
W El Hamdani, K Hadami, M Bensaid, H El Ahanidi, A Ameur, A Filali Maltouf, M Abbar, M Attaleb, A Albouzidi, M El Mzibri
The epidermal growth factor receptor (EGFR) is involved in the regulation of several cellular processes and in the development of many human cancers. Somatic mutations of EGFR at tyrosine kinase domain have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. In this study, we evaluated the frequency of point mutations in EGFR for future use of TKI in clinical treatment of bladder cancer. A total, 50 Moroccan patient specimens with bladder cancer and 48 healthy controls were analysed for EGFR mutations in the region delimiting exons 18-21 by PCR amplification and direct sequencing...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28718011/case-series-on-the-association-between-blood-levels-and-side-effects-of-afatinib-maleate
#4
Junya Sato, Naoto Morikawa, Ryosuke Chiba, Satoru Nihei, Satoshi Moriguchi, Heisuke Saito, Kohei Yamauchi, Kenzo Kudo
PURPOSE: Afatinib maleate (AFA) is a second-generation, tyrosine kinase inhibitor (TKI) treatment for specific variants of non-small cell lung cancer exhibiting epidermal growth factor receptor (EGFR) mutations. In this study, we measured the blood AFA levels in six patients with lung cancer and investigated the association between blood levels and side effects of this drug. METHODS: The study subjects were patients who were administered AFA for non-small cell lung cancer...
July 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28712979/clinical-implications-of-the-t790m-mutation-in-disease-characteristics-and-treatment-response-in-patients-with-epidermal-growth-factor-receptor-egfr-mutated-non-small-cell-lung-cancer%C3%A2-nsclc
#5
Daria Gaut, Myung Shin Sim, Yuguang Yue, Brian R Wolf, Phillip A Abarca, James M Carroll, Jonathan W Goldman, Edward B Garon
BACKGROUND: The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown. MATERIALS AND METHODS: Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation-specific TKI...
June 20, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28710746/osimertinib-a-review-in-t790m-positive-advanced-non-small-cell-lung-cancer
#6
REVIEW
Yvette N Lamb, Lesley J Scott
Osimertinib (Tagrisso™) is an oral, CNS-active, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets EGFR TKI-sensitizing mutations and, crucially, the T790M mutation that often underlies acquired resistance to EGFR TKI therapy. Osimertinib has been approved in numerous countries for use in patients with T790M-positive advanced NSCLC. In the pivotal, international AURA3 trial in patients with T790M-positive advanced NSCLC who had disease progression after EGFR TKI therapy, osimertinib treatment significantly prolonged progression-free survival (PFS; primary endpoint) compared with platinum-pemetrexed therapy at the time of the primary analysis...
July 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28708233/treatment-in-egfr-mutated-non-small-cell-lung-cancer-how-to-block-the-receptor-and-overcome-resistance-mechanisms
#7
Claudia Proto, Giuseppe Lo Russo, Giulia Corrao, Monica Ganzinelli, Francesco Facchinetti, Roberta Minari, Marcello Tiseo, Marina Chiara Garassino
In non-small cell lung cancer (NSCLC), the identification of epidermal growth factor receptor (EGFR) mutations and the parallel development of EGFR tyrosine kinase inhibitors (TKIs) have radically changed the therapeutic management strategies. Currently, erlotinib, gefitinib, and afatinib are all approved as standard first-line treatment in EGFR-mutated NSCLC. However, despite the proven efficacy, some EGFR-mutated NSCLCs do not respond to EGFR TKIs, while some patients, after a favorable and prolonged response to EGFR TKIs, inevitably progress within about 10-14 months...
July 1, 2017: Tumori
https://www.readbyqxmd.com/read/28704781/impacts-of-egfr-mutation-and-egfr-tkis-on-incidence-of-brain-metastases-in-advanced-non-squamous-nsclc
#8
Bao-Xiao Wang, Wei Ou, Xiao-Yong Mao, Zui Liu, Hui-Qi Wu, Si-Yu Wang
OBJECTIVE: Brain metastases remain lethal in lung cancer patients. The impacts of epidermal growth factor receptor (EGFR) mutations and EGFR tyrosine kinase inhibitors (TKIs) on the incidence of brain metastases in patients with advanced non-squamous non-small cell lung cancer (NSCLC) are still uncertain. PATIENTS AND METHODS: A total of 1672 patients with advanced non-squamous NSCLC with a definitive report on EGFR mutation status between January 2005 and June 2013 were retrospectively analyzed...
June 29, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28701107/overcoming-resistance-to-egfr-tyrosine-kinase-inhibitors-in-lung-cancer-focusing-on-non-t790m-mechanisms
#9
Kenichi Suda, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
Despite initial dramatic efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer patients, emergence of acquired resistance is almost inevitable. The EGFR T790M secondary mutation that accounts for ~50% of resistance is now treatable with osimertinib. However, for the remaining 50% of patients who develop resistance mechanisms other than T790M mutation, cytotoxic chemotherapies are still the standard of care and novel treatment strategies are urgently needed. Areas covered: In this review, we discuss current experimental and clinical evidence to develop better treatment strategies to overcome or prevent acquired resistance to EGFR-TKIs in lung cancers, focusing on non-T790M mechanisms...
July 13, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28699260/australian-recommendations-for-egfr-t790m-testing-in-advanced-non-small-cell-lung-cancer
#10
REVIEW
Thomas John, Jeffrey J Bowden, Stephen Clarke, Stephen B Fox, Kerryn Garrett, Keith Horwood, Christos S Karapetis
First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as first-line therapy in patients with non-small cell lung cancer (NSCLC) harboring a sensitizing mutation in the EGFR gene. Unfortunately, resistance to these therapies often occurs within 10 months of commencing treatment and is mostly commonly due to the development of the EGFR T790M mutation. Treatment with the third-generation EGFR TKI, osimertinib can prolong progression free survival in patients with the T790M mutation, so it is important to determine the resistance mechanism in order to plan ongoing therapeutic strategies...
July 12, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28693210/resistance-to-epithelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-a-patient-with-transformation-from-lung-adenocarcinoma-to-small-cell-lung-cancer-a-case-report
#11
Liying Fang, Jian He, Jingwen Xia, Liang Dong, Xiujuan Zhang, Yaqin Chai, Ying Li, Mengjie Niu, Tianxing Hang, Shengqing Li
First-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the treatment of non-small cell lung cancer (non-SCLC) with EGFR-sensitive mutations. However, acquired resistance to these drugs was inevitable. The transformation of lung adenocarcinoma to SCLC following treatment with EGFR-TKIs is a rare phenomenon that contributes to resistance to EGFR-TKIs. The present case concerns a 74-year-old man previously diagnosed with and treated for pneumonia; however, this was later pathologically confirmed as lung adenocarcinoma by transbronchial lung biopsy...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28685062/the-level-of-serum-carcinoembryonic-antigen-is-a-surrogate-marker-for-the-efficacy-of-egfr-tkis-but-is-not-an-indication-of-acquired-resistance-to-egfr-tkis-in-nsclc-patients-with-egfr-mutationsm
#12
Jingquan Han, Yuzhang Li, Shouqiang Cao, Qing Dong, Guibin Zhao, Xiangyu Zhang, Jian Cui
The aim of the present study was to define the relationship between carcinoembryonic antigen (CEA) and survival in non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and to investigate whether the level of serum CEA is related to the mechanism for acquisition of resistance to EGFR-TKIs. A total of 100 patients with advanced NSCLC (stage IIIB or stage IV) and harboring EGFR mutations were included. All patients received erlotinib or gefitinib treatment...
July 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28684311/hippo-effector-yap-directly-regulates-the-expression-of-pd-l1-transcripts-in-egfr-tki-resistant-lung-adenocarcinoma
#13
Byung Soo Lee, Dong Il Park, Da Hye Lee, Jeong Eun Lee, Min-Kyung Yeo, Yeon Hee Park, Dae Sik Lim, Wonyoung Choi, Da Hye Lee, Geon Yoo, Han-Byul Kim, Dahyun Kang, Jae Young Moon, Sung Soo Jung, Ju Ock Kim, Hee Sun Park, Chaeuk Chung
Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways...
July 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28683123/reverse-epithelial-mesenchymal-transition-contributes-to-the-regain-of-drug-sensitivity-in-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer-cells
#14
An-Fu Lee, Man-Chin Chen, Chao-Ju Chen, Chih-Jen Yang, Ming-Shyang Huang, Yu-Peng Liu
Tyrosine kinase inhibitors (TKIs) are currently the first-line treatment for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. These patients receive platinum-based chemotherapy as the second-line treatment after they develop resistance to TKIs. Many patients regain sensitivity to the TKIs used in the first-line treatment after the failure of chemotherapy. However, the molecular mechanism for the regain of TKI sensitivity is largely unknown. In this study, we established gefitinib-resistant PC9 and HCC827 cell lines, which did not harbor the EGFR T790M mutation and MET amplification but exhibited the epithelial-mesenchymal transition (EMT) phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28678431/epithelial-to-mesenchymal-transition-and-its-role-in-egfr-mutant-lung-adenocarcinoma-and-idiopathic-pulmonary-fibrosis
#15
REVIEW
Yuji Sakuma
Lung adenocarcinoma cells with activating epidermal growth factor receptor (EGFR) mutations are highly dependent upon EGFR signaling for survival and undergo apoptosis when EGFR signaling is inhibited by tyrosine kinase inhibitor (TKI) treatment. Paradoxically, EGFR-mutant lung adenocarcinomas have subpopulations of cells that can survive independently of activated EGFR. Such EGFR-independent EGFR-mutant cancer cells include cells that have undergone epithelial-to-mesenchymal transition (EMT) or transformed to small cell lung cancer, which almost completely lack EGFR dependency...
July 5, 2017: Pathology International
https://www.readbyqxmd.com/read/28676644/blocking-autophagy-improves-the-anti-tumor-activity-of-afatinib-in-lung-adenocarcinoma-with-activating-egfr-mutations-in-vitro-and-in-vivo
#16
Xiangxiang Hu, Si Shi, Huan Wang, Xiaochen Yu, Qian Wang, Shanshan Jiang, Dianwen Ju, Li Ye, Meiqing Feng
Afatinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, afatinib's clinical application is still hampered by acquired resistance. Recently, autophagy is considered as an important mechanism of resistance to TKI. Herein, we investigated the autophagy induction as well as its influence on anti-lung adenocarcinoma activity of afatinib in two activating EGFR-mutants H1975 and H1650 cells. First, Growth inhibition and caspase-dependent apoptosis were observed in afatinib-treated H1975 and H1650 cells...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28676222/optimal-management-of-egfr-mutant-non-small-cell-lung-cancer-with-disease-progression-on-first-line-tyrosine-kinase-inhibitor-therapy
#17
REVIEW
Bin-Chi Liao, Chia-Chi Lin, Jih-Hsiang Lee, James Chih-Hsin Yang
The first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, and the second-generation EGFR-TKI, afatinib, have all been approved as standard first-line treatments for advanced EGFR-mutant non-small cell lung cancer (NSCLC) based on superior progression-free survival results compared to platinum doublet chemotherapy regimens. Acquired resistance to an EGFR-TKI inevitably develops after a period of effective drug treatment. After tumor progression, many combination therapy regimens that include an EGFR-TKI, or EGFR-TKI monotherapy, have been tested in prospective trials with the aim of extending survival...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28676213/urine-circulating-tumor-dna-ctdna-detection-of-acquired-egfr-t790m-mutation-in-non-small-cell-lung-cancer-an-outcomes-and-total-cost-of-care-analysis
#18
Jacob Sands, Qianyi Li, John Hornberger
OBJECTIVES: Third-generation tyrosine kinase inhibitors (TKIs) have proven effective in patients with the acquired EGFR T790M resistance mutation who progress on prior EGFR TKI therapy. Median progression-free survival (PFS) on a 3rd-gen TKI was 9-10 months for T790M+ patients compared to 2.8 months for T790M- patients. PFS is similar regardless of the specimen used to assess T790M, such as tissue, plasma, or urine ctDNA. This study aimed to assess the total cost of care of a urine-testing strategy (UTS) versus a tissue-testing strategy (TTS) for T790M detection, in patients with EGFR-mutation positive lung adenocarcinoma and progression on prior TKI therapy...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28660482/efficacy-of-tyrosine-kinase-inhibitors-in-egfr-mutant-lung-cancer-women-in-a-real-world-setting-the-world07-database
#19
J Remon, D Isla, P Garrido, J de Castro, M Majem, N Viñolas, A Artal, E Carcereny, M R García-Campelo, P Lianes, M Provencio, O Juan, P Diz, R Blanco, R Lopez-Castro, I Maestu, C Vadell, E Felip
BACKGROUND: The WORLD07 project is a female specific database to assess the characteristics of women with lung cancer. METHODS: WORLD07 database sets up in 2007, and prospectively stores clinical characteristics, treatment, outcome, and follow-up of lung cancer women. All women with epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer (NSCLC) were selected for this analysis. RESULTS: From October 2007 to December 2012, a total of 1775 NSCLC women were recruited...
June 28, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28652772/epidermal-growth-factor-receptor-exon-20-mutation-in-lung-cancer-types-incidence-clinical-features-and-impact-on-treatment
#20
Vanita Noronha, Anuradha Choughule, Vijay M Patil, Amit Joshi, Rajiv Kumar, Deepa Susan Joy Philip, Shripad Banavali, Amit Dutt, Kumar Prabhash
BACKGROUND: There are limited data available on the treatment and outcome of epidermal growth factor receptor (EGFR) exon 20-mutated lung cancer patients. Hence, we planned an analysis of the demographic details, clinical profile and survival of lung cancer patients with exon 20 mutations. We compared our results to patients with EGFR tyrosine kinase inhibitor (TKI)-sensitizing activating and EGFR/anaplastic lymphoma kinase (ALK)-negative mutations. METHODS: This was a retrospective analysis of lung cancer patients who were treated at our center between January 2010 and August 2014...
2017: OncoTargets and Therapy
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