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https://read.qxmd.com/read/30888598/clinical-management-of-non-small-cell-lung-cancer-with-concomitant-egfr-mutations-and-alk-rearrangements-efficacy-of-egfr-tyrosine-kinase-inhibitors-and-crizotinib
#1
Yiming Zhao, Shuyuan Wang, Bo Zhang, Rong Qiao, Jianlin Xu, Lele Zhang, Yanwei Zhang, Baohui Han
BACKGROUND: Patients harboring concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) arrangements constitute a small subgroup of non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR tyrosine kinase inhibitors (TKIs) and the ALK-specific TKI crizotinib in these patients has not been well-established. OBJECTIVE: This study investigated the efficacy of targeted therapies in these patients compared with patients with EGFR or ALK alterations alone...
March 19, 2019: Targeted Oncology
https://read.qxmd.com/read/30887673/re-biopsy-and-liquid-biopsy-for-patients-with-non-small-cell-lung-cancer-after-egfr-tyrosine-kinase-inhibitor-failure
#2
Juan Zhou, Chao Zhao, Jing Zhao, Qi Wang, Xiangling Chu, Jiayu Li, Fei Zhou, Shengxiang Ren, Xuefei Li, Chunxia Su, Caicun Zhou
BACKGROUND: Re-biopsy is important for exploring resistance mechanisms, especially for non-small cell lung cancer (NSCLC) patients who develop resistance to EGFR-tyrosine kinase inhibitors (TKIs). Liquid biopsy using circulating tumor DNA has come into use for this purpose. This retrospective study investigated the status of re-biopsy and liquid biopsy in NSCLC patients with EGFR mutations and evaluated their effect on clinical strategies and prognosis. METHODS: Five hundred fifty-five NSCLC patients with resistance to EGFR-TKIs were included and divided into three groups: re-biopsy, liquid biopsy, and no re-biopsy...
March 18, 2019: Thoracic Cancer
https://read.qxmd.com/read/30885357/repeat-biopsy-procedures-and-t790m-rates-after-afatinib-gefitinib-or-erlotinib-therapy-in-patients-with-lung-cancer
#3
Kangkook Lee, Youjin Kim, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Yoon-La Choi, Jong-Mu Sun
OBJECTIVES: Afatinib, a second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is used for EGFR-mutant non-small cell lung cancer (NSCLC). However, there are few reports about its resistance mechanisms. The aims of this study are to evaluate resistance mechanisms of afatinib compared with other TKIs and analyze the performance of repeat biopsy which is critical for subsequent treatment. MATERIALS AND METHODS: We screened EGFR-mutant NSCLC patients who started first-line afatinib, gefitinib, or erlotinib from 2014 to 2016, and included patients who acquired resistance...
April 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://read.qxmd.com/read/30885350/efficacy-and-long-term-survival-of-advanced-lung-adenocarcinoma-patients-with-uncommon-egfr-mutations-treated-with-1st-generation-egfr-tkis-compared-with-chemotherapy-as-first-line-therapy
#4
Haixia Li, Chenyu Wang, Ziqi Wang, Yabo Hu, Guowei Zhang, Mina Zhang, Xuanxuan Zheng, Xiaojuan Zhang, Jinbo Yang, Zhiyong Ma, Huijuan Wang
PURPOSE: This study aims to understand the effects and long-term survival of 1st generation epithelial growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)or platinum-based chemotherapy as first-line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations. PATIENTS AND METHODS: Specimens from 4276 advanced (IIIB/IV) patients were diagnosed with lung adenocarcinoma and underwent EGFR gene detection at the Affiliated Cancer Hospital of Zhengzhou University...
April 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://read.qxmd.com/read/30885342/erlotinib-versus-gemcitabine-cisplatin-in-chinese-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-crossover-extension-and-post-hoc-analysis-of-the-ensure-study
#5
Yi-Long Wu, Caicun Zhou, Shun Lu, Shukui Qin, Hongming Pan, Gang Wu, Ying Cheng, Xiaoqing Liu, Baohui Han, Yunzhong Zhu, Zhaoyang Zhong, Cheng Huang, Lei Chen, Houjie Liang, Enxiao Li, Guoliang Jiang
OBJECTIVES: Sequential combination of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and chemotherapy has shown greater benefits than either treatment alone in non-small-cell lung cancer (NSCLC). In this follow-up of the ENSURE study, we evaluated progression-free survival (PFS) with first-line erlotinib followed by chemotherapy at progression versus the inverse treatment sequence in 175 Chinese patients with EGFR mutation-positive NSCLC. MATERIALS AND METHODS: Forty-five of the 175 patients included in the follow-up analysis experienced progressive disease (PD)...
April 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://read.qxmd.com/read/30878600/concurrent-driver-gene-mutations-as-negative-predictive-factors-in-epidermal-growth-factor-receptor-positive-non-small-cell-lung-cancer
#6
Minjiang Chen, Yan Xu, Jing Zhao, Wei Zhong, Li Zhang, Yalan Bi, Mengzhao Wang
BACKGROUND: Tyrosine kinase inhibitors (TKIs) are clinically effective in non-small cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) oncogene mutations. Genetic factors, other than EGFR sensitive mutations, that allow prognosis of TKI treatment remain undefined. METHODS: We retrospectively screened 423 consecutive patients with advanced NSCLC and EGFR 19del or 21L858R mutations. A total of 71 patients whose progression-free survivals (PFS) were shorter than 6 months or longer than 24 months were included and stratified into separate groups...
March 14, 2019: EBioMedicine
https://read.qxmd.com/read/30876460/co-administration-of-20-s-protopanaxatriol-g-ppt-and-egfr-tki-overcomes-egfr-tki-resistance-by-decreasing-scd1-induced-lipid-accumulation-in-non-small-cell-lung-cancer
#7
Quanfu Huang, Qiuguo Wang, Dong Li, Xiao Wei, Yijuan Jia, Zheng Zhang, Bo Ai, Xiaonian Cao, Tao Guo, Yongde Liao
BACKGROUND: Non-small cell lung cancer (NSCLC) patients with sensitive epidermal growth factor receptor (EGFR) mutations are successfully treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs); however, resistance to treatment inevitably occurs. Given lipid metabolic reprogramming is widely known as a hallmark of cancer and intimately linked with EGFR-stimulated cancer growth. Activation of EGFR signal pathway increased monounsaturated fatty acids (MUFA) and lipid metabolism key enzyme Stearoyl-CoA Desaturase 1 (SCD1) expression...
March 15, 2019: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/30875928/newer-generation-egfr-inhibitors-in-lung-cancer-how-are-they-best-used
#8
REVIEW
Tri Le, David E Gerber
The FLAURA trial established osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), as a viable first-line therapy in non-small cell lung cancer (NSCLC) with sensitizing EGFR mutations, namely exon 19 deletion and L858R. In this phase 3 randomized, controlled, double-blind trial of treatment-naïve patients with EGFR mutant NSCLC, osimertinib was compared to standard-of-care EGFR TKIs (i.e., erlotinib or gefinitib) in the first-line setting. Osimertinib demonstrated improvement in median progression-free survival (18...
March 15, 2019: Cancers
https://read.qxmd.com/read/30875919/clinical-characteristics-of-osimertinib-responder-in-non-small-cell-lung-cancer-patients-with-egfr-t790m-mutation
#9
Akihiro Yoshimura, Tadaaki Yamada, Naoko Okura, Takayuki Takeda, Kazuki Hirose, Yutaka Kubota, Shinsuke Shiotsu, Osamu Hiranuma, Yusuke Chihara, Nobuyo Tamiya, Yoshiko Kaneko, Junji Uchino, Koichi Takayama
Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) in patients with the EGFR -T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown. In this retrospective study, 27 NSCLC patients with the EGFR -T790M mutation were enrolled at five institutions in Japan. Among several parameters tested, the progression-free survival (PFS) associated with the initial EGFR-TKIs was positively correlated with the PFS after osimertinib treatment ( p = 0...
March 15, 2019: Cancers
https://read.qxmd.com/read/30872465/mutation-profile-of-resected-egfr-mutated-lung-adenocarcinoma-by-next-generation-sequencing
#10
Ze-Rui Zhao, Yao-Bin Lin, Calvin S H Ng, Rong Zhang, Xue Wu, Qiuxiang Ou, Wendan Chen, Wen-Jie Zhou, Yong-Bin Lin, Xiao-Dong Su, Yang W Shao, Hao Long
BACKGROUND: The efficacy of adjuvant targeted therapy for operable lung cancer is still under debate. Comprehensive genetic profiling is needed for detecting co-mutations in resected epidermal growth factor receptor ( EGFR )-mutated lung adenocarcinoma (ADC), which may interfere the efficacy of adjuvant tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: Mutation profiling of 416 cancer-relevant genes was conducted for 139 resected stage I-IIIa lung ADCs with EGFR mutations using targeted next-generation sequencing...
March 14, 2019: Oncologist
https://read.qxmd.com/read/30872380/tas-121-a-selective-mutant-egfr-inhibitor-shows-activity-against-tumors-expressing-various-egfr-mutations-including-t790m-and-uncommon-mutations-g719x
#11
Kimihiro Ito, Makoto Nishio, Masanori Kato, Haruyasu Murakami, Yoshimi Aoyagi, Yuichiro Ohe, Takashige Okayama, Akihiro Hashimoto, Hirokazu Ohsawa, Gotaro Tanaka, Katsumasa Nonoshita, Satoru Ito, Kenichi Matsuo, Kazutaka Miyadera
TAS-121 is a novel orally active selective covalent inhibitor of the mutant epidermal growth factor receptor (EGFR). We performed preclinical characterization of TAS-121 and compared its efficacy and selectivity for common EGFR mutations (Ex19del and L858R), first- and second- generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance mutation (T790M), and uncommon mutations (G719X and L861Q) with those of other EGFR-TKIs. We also commenced investigation of the clinical benefits of TAS-121. The 50% inhibitory concentration (IC50) for intracellular EGFR phosphorylation was determined by using Jump-In GripTite HEK293 cells transiently transfected with EGFR expression vectors...
March 14, 2019: Molecular Cancer Therapeutics
https://read.qxmd.com/read/30864291/different-incidence-of-interstitial-lung-disease-according-to-different-kinds-of-egfr-tyrosine-kinase-inhibitors-administered-immediately-before-and-or-after-anti-pd-1-antibodies-in-lung-cancer
#12
Takahiro Uchida, Kyoichi Kaira, Ou Yamaguchi, Atsuto Mouri, Ayako Shiono, Yu Miura, Kosuke Hashimoto, Fuyumi Nishihara, Yoshitake Murayama, Kunihiko Kobayashi, Hiroshi Kagamu
BACKGROUND: The aim of our study was to retrospectively assess the incidence of interstitial lung disease (ILD) related to EGFR-tyrosine kinase inhibitor (TKI) treatment immediately before and/or after the administration of a PD-1 antibody. METHODS: We analyzed the data of 26 patients who underwent treatment with EGFR-TKIs immediately before and/or after the administration of an anti-PD-1 antibody. RESULTS: Four out of the 26 patients developed ILD during EGFR-TKI treatment: three patients during the administration of osimertinib immediately after, and one during afatinib immediately before treatment with an anti-PD-1 antibody...
March 12, 2019: Thoracic Cancer
https://read.qxmd.com/read/30864019/data-from-real-world-to-evaluate-the-efficacy-of-osimertinib-in-non-small-cell-lung-cancer-patients-with-central-nervous-system-metastasis
#13
P Xing, Y Mu, X Hao, Y Wang, J Li
OBJECTIVES: Central nervous system (CNS) metastases are very common in patients with non-small-cell lung cancer (NSCLC). We aimed to explore the clinical impact of osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), on CNS metastases in patients with advanced NSCLC in real-world setting. METHODS: Patients with advanced NSCLC who received osimertinib after progression of early-generation EGFR-TKIs and CNS metastases on baseline brain scan were retrospectively collected...
March 12, 2019: Clinical & Translational Oncology
https://read.qxmd.com/read/30863108/first-line-tyrosine-kinase-inhibitors-in-egfr-mutation-positive-non-small-cell-lung-cancer-a-network-meta-analysis
#14
REVIEW
Marscha S Holleman, Harm van Tinteren, Harry Jm Groen, Maiwenn J Al, Carin A Uyl-de Groot
Background: EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib have proven efficacy in terms of progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, an overall view for comparing efficacy and toxicity on a meta-level is lacking. This study compared efficacy and toxicity of first-line treatment with five different EGFR-TKIs by conducting a network meta-analysis (NMA)...
2019: OncoTargets and Therapy
https://read.qxmd.com/read/30857358/the-presence-of-concomitant-mutations-affects-the-activity-of-egfr-tyrosine-kinase-inhibitors-in-egfr-mutant-non-small-cell-lung-cancer-nsclc-patients
#15
Anna Maria Rachiglio, Francesca Fenizia, Maria Carmela Piccirillo, Domenico Galetta, Lucio Crinò, Bruno Vincenzi, Emiddio Barletta, Carmine Pinto, Francesco Ferraù, Matilde Lambiase, Agnese Montanino, Cristin Roma, Vienna Ludovini, Elisabetta Sara Montagna, Antonella De Luca, Gaetano Rocco, Gerardo Botti, Francesco Perrone, Alessandro Morabito, Nicola Normanno
Recent findings suggest that a fraction of EGFR-mutant non-small-cell lung cancers (NSCLC) carry additional driver mutations that could potentially affect the activity of EGFR tyrosine kinase inhibitors (TKIs). We investigated the role of concomitant KRAS, NRAS, BRAF, PIK3CA, MET and ERBB2 mutations (other mutations) on the outcome of 133 EGFR mutant patients, who received first-line therapy with EGFR TKIs between June 2008 and December 2014. Analysis of genomic DNA by Next Generation Sequencing (NGS) revealed the presence of hotspot mutations in genes other than the EGFR, including KRAS, NRAS, BRAF, ERBB2, PIK3CA, or MET, in 29/133 cases (21...
March 10, 2019: Cancers
https://read.qxmd.com/read/30855441/bim-deletion-polymorphism-predicts-poor-response-to-egfr-tkis-in-nonsmall-cell-lung-cancer-an-updated-meta-analysis
#16
Wenxia Su, Xiaoyun Zhang, Xin Cai, Meiyu Peng, Fengbin Wang, Yuliang Wang
BACKGROUND: A germline deletion in BIM (B cell lymphoma-2-like 11) gene has been shown to impair the apoptotic response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in vitro but its impact on response to EGFR-TKIs in patients of nonsmall cell lung cancer (NSCLC) remains controversial. METHODS: Eligible literature were searched and screened. Objective response rate (ORR) and disease control rate (DCR) were extracted and aggregated with odds ratio (OR)...
March 2019: Medicine (Baltimore)
https://read.qxmd.com/read/30847464/severe-immune-related-adverse-events-are-common-with-sequential-pd-l-1-blockade-and-osimertinib
#17
A J Schoenfeld, K C Arbour, H Rizvi, A N Iqbal, S M Gadgeel, J Girshman, M G Kris, G J Riely, H A Yu, M D Hellmann
BACKGROUND: Concurrent PD-(L)1 plus osimertinib is associated with severe immune related adverse events (irAE) in EGFR mutant NSCLC. Now that PD-(L)1 inhibitors are routinely used as adjuvant and first-line treatments, sequential PD-(L)1 inhibition followed by osimertinib use may become more frequent and have unforeseen serious toxicity. METHODS: We identified patients with EGFR-mutant NSCLC who were treated with PD-(L)1 blockade and EGFR-TKIs, irrespective of drug or sequence of administration (total n = 126)...
March 7, 2019: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://read.qxmd.com/read/30825234/spock1-contributes-to-the-third-generation-egfr-tyrosine-kinase-inhibitors-resistance-in-lung-cancer
#18
Yujuan Gao, Min Yu, Miao Ma, Yi Zhuang, Xiaohua Qiu, Qi Zhao, Jinghong Dai, Hourong Cai, Xin Yan
INTRODUCTION: Explanation of the mechanism of resistance to third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and the development of a novel strategy for drug resistance are imperative in third-generation EGFR-TKIs-resistant non-small cell lung cancer (NSCLC). SPOCK1 was found to be abnormally expressed in various tumors including lung cancer, however, there was no study focused on the role of SPOCK1 in third-generation EGFR-TKIs resistant lung cancer cells...
March 1, 2019: Journal of Cellular Biochemistry
https://read.qxmd.com/read/30823937/identification-of-genetic-alterations-associated-with-primary-resistance-to-egfr-tkis-in-advanced-non-small-cell-lung-cancer-patients-with-egfr-sensitive-mutations
#19
Fang Wang, Xia-Yao Diao, Xiao Zhang, Qiong Shao, Yan-Fen Feng, Xin An, Hai-Yun Wang
BACKGROUND: Identification of activated epidermal growth factor receptor (EGFR) mutations and application of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have greatly changed the therapeutic strategies of non-small-cell lung cancer (NSCLC). However, the long-term efficacy of EGFR-TKI therapy is limited due to the development of drug resistance. The aim of this study was to investigate the correlation between the aberrant alterations of 8 driver genes and the primary resistance to EGFR-TKIs in advanced NSCLC patients with activated EGFR mutations...
March 2, 2019: Cancer Communications
https://read.qxmd.com/read/30821083/evaluation-of-osimertinib-efficacy-according-to-body-surface-area-and-body-mass-index-in-patients-with-non-small-cell-lung-cancer-harboring-an-egfr-mutation-a-prospective-observational-study
#20
Taihei Ono, Satoshi Igawa, Takahiro Ozawa, Masashi Kasajima, Mikiko Ishihara, Yasuhiro Hiyoshi, Seiichiro Kusuhara, Noriko Nishinarita, Tomoya Fukui, Masaru Kubota, Jiichiro Sasaki, Mitsufuji Hisashi, Masato Katagiri, Katsuhiko Naoki
BACKGROUND: Osimertinib is recommended for non-small cell lung cancer (NSCLC) patients with EGFR mutation; however, it is unclear whether body size variables affect the efficacy of osimertinib in such patients. This study assessed the potential effect of body surface area (BSA) and body mass index (BMI) on osimertinib chemotherapy in patients with T790M-positive advanced NSCLC who progress on prior EGFR-tyrosine kinase inhibitors (TKIs). METHODS: We conducted a prospective observational cohort study...
February 28, 2019: Thoracic Cancer
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