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Egfr-tki treatment for lung cancer

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https://www.readbyqxmd.com/read/28798090/egfr-tyrosine-kinase-inhibitors-versus-chemotherapy-in-egfr-wild-type-pre-treated-advanced-nonsmall-cell-lung-cancer-in%C3%A2-daily-practice
#1
Pascale Tomasini, Solenn Brosseau, Julien Mazières, Jean-Philippe Merlio, Michèle Beau-Faller, Jean Mosser, Marie Wislez, L'Houcine Ouafik, Benjamin Besse, Isabelle Rouquette, Didier Debieuvre, Fabienne Escande, Virginie Westeel, Clarisse Audigier-Valette, Pascale Missy, Alexandra Langlais, Frank Morin, Denis Moro-Sibilot, Gérard Zalcman, Fabrice Barlesi
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are approved for second-line treatment of EGFR wild-type (EGFR-wt) nonsmall cell lung cancer (NSCLC). However, results from randomised trials performed to compare EGFR-TKIs with chemotherapy in this population did not show any survival benefit. In the era of immunotherapy, many drugs are approved for second-line treatment of EGFR-wt NSCLC and there is a need to reassess the role of EGFR-TKIs in this setting.The Biomarkers France study is a large nationwide cohort of NSCLC patients tested for EGFR mutations...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28794650/treating-egfr-mutation-resistance-in-non-small-cell-lung-cancer-role-of-osimertinib
#2
REVIEW
Valentina Mazza, Federico Cappuzzo
The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR-mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR-wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28781781/responses-to-crizotinib-and-chemotherapy-in-patients-with-lung-adenocarcinoma-harboring-a-concomitant-egfr-mutation-and-alk-gene-rearrangement-a-case-report-and-review-of-the-literature
#3
Yuping Li, Shanshan Su, Guoping Cai, Quan Lin, Ying Zhou, Jinsheng Ouyang, Bicheng Chen, Junru Ye, Xiuling Wu, Chengshui Chen
Previous studies have indicated that, in lung cancers, the gene rearrangement of ALK is mutually exclusive with mutations in the epidermal growth factor receptor (EGFR) gene. However, the coexistence of EML4-ALK fusions and EGFR mutations (double positive) has been occasionally reported, with frequencies ranging from 0-8%. Currently, no consensus standard therapy exists for tumors with double positive mutations. In the present case report, the case is described of a 53-year-old woman with stage IV lung adenocarcinoma, harboring a concomitant EGFR mutation and ALK gene rearrangement, who was refractory to gefitinib administration but demonstrated a good response to crizotinib and pemetrexed chemotherapy...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28777825/beyond-disease-progression-clinical-outcomes-after-egfr-tkis-in-a-cohort-of-egfr-mutated-nsclc-patients
#4
Roxana Alina Tudor, Adrijana D'Silva, Alain Tremblay, Paul MacEachern, Don Morris, Darren Brenner, Karen Kopciuk, Dafydd Gwyn Bebb
PURPOSE: Treatment and clinical-outcomes were described in a sub-cohort of non-small-cell lung cancer (NSCLC) patients with disease-progression (PD) after epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment. PATIENTS AND METHODS: We retrospectively analyzed a single-institutional EGFR mutation positive (EGFRmut+) NSCLC cohort for post-TKI-PD management, and assessed overall survival (OS) and post-progression survival (PPS). All de-novo (first lung-cancer occurrence) stage IIIA-IV patients, as well as de-novo stage IV subset was analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28776311/continued-egfr-tki-with-concurrent-radiotherapy-to-improve-time-to-progression-ttp-in-patients-with-locally-progressive-non-small-cell-lung-cancer-nsclc-after-front-line-egfr-tki-treatment
#5
Y Wang, Y Li, L Xia, K Niu, X Chen, D Lu, R Kong, Z Chen, J Sun
BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment. METHODS: Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression...
August 3, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28758857/brain-metastases-in-non-small-cell-lung-cancer-patients-on-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-symptom-and-economic-burden
#6
Ancilla W Fernandes, Bingcao Wu, Ralph M Turner
OBJECTIVE: This study describes the symptom and economic burden associated with brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) receiving epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs). METHODS: This retrospective study included adults with ≥2 medical claims, within 90 days, for lung cancer and ≥1 administration of EGFR-TKIs. Based on ICD-9 codes, patients were stratified into cohorts by type of metastases (BM, other metastases [OM], or no metastases [NM]), and by when the metastasis diagnosis occurred (synchronous or asynchronous)...
July 31, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28757172/polyphyllin-vii-increases-sensitivity-to-gefitinib-by-modulating-the-elevation-of-p21-in-acquired-gefitinib-resistant-non-small-cell-lung-cancer
#7
Honggang Wang, Zhenghua Fei, Hao Jiang
Blockade of EGFR with reversible EGFR tyrosine kinase inhibitors (TKIs) is considered the frontline strategy for advanced NSCLC with EGFR mutations. However, acquired resistance to EGFR-TKI has been observed, resulting in disease progression and limited clinical benefit. Polyphyllin VII is the main member of polyphyllin family, which has been demonstrated to show strong anticancer activity against carcinomas. The sensitizing effect and underlying mechanism of Polyphyllin VII against acquired EGFR-TKI resistant NSCLC are still unexplored...
June 30, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28756224/treatment-with-a-programmed-cell-death-1-specific-antibody-has-little-effect-on-afatinib-and-naphthalene-induced-acute-pneumonitis-in-mice
#8
Naoki Hamada, Toyoshi Yanagihara, Kunihiro Suzuki, Saiko Ogata-Suetsugu, Eiji Harada, Hironori Mikumo, Masako Arimura-Omori, Yoichi Nakanishi
Although several antibodies developed to target programmed cell death-1 (PD-1) and its ligand (PD-L1) have demonstrated great promise for the treatment of non-small cell lung cancer (NSCLC), and other malignancies, these therapeutic antibodies can cause pneumonitis. Furthermore, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-induced pneumonitis was reported after treatment with anti PD-1 antibodies. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis through a neutrophil-dependent mechanism...
July 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28749535/inhibition-of-histone-deacetylases-sensitizes-egfr-tki-resistant-non-small-cell-lung-cancer-cells-to-erlotinib-in-vitro-and-in-vivo
#9
Weiwei Yu, Weiqiang Lu, Guoliang Chen, Feixiong Cheng, Hui Su, Yihua Chen, Mingyao Liu, Xiufeng Pang
BACKGROUND AND PURPOSE: Intrinsic and/or acquired resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly occurs in patients with non-small-cell lung cancer (NSCLC). Here, we develop a combined therapy of histone deacetylase inhibition by a novel HDAC inhibitor, YF454A, with erlotinib to overcome EGFR-TKI resistance in NSCLC. EXPERIMENTAL APPROACH: The sensitization of erlotinib by YF454A was examined in a panel of EGFR-TKI-resistant NSCLC cell lines in vitro and two different erlotinib-resistant NSCLC xenograft mouse models in vivo...
July 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28747569/acquisition-of-the-t790m-resistance-mutation-during-afatinib-treatment-in-egfr-tyrosine-kinase-inhibitor-na%C3%A3-ve-patients-with-non-small-cell-lung-cancer-harboring-egfr-mutations
#10
Kentaro Tanaka, Kaname Nosaki, Kohei Otsubo, Koichi Azuma, Shinya Sakata, Hiroshi Ouchi, Ryotaro Morinaga, Hiroshi Wataya, Akiko Fujii, Noriaki Nakagaki, Nobuko Tsuruta, Masafumi Takeshita, Eiji Iwama, Taishi Harada, Yoichi Nakanishi, Isamu Okamoto
The T790M secondary mutation of the epidermal growth factor receptor (EGFR) gene accounts for 50% to 60% of cases of resistance to the first-generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. The prevalence of T790M in EGFR mutation-positive patients who acquire resistance to the irreversible, second-generation EGFR-TKI afatinib has remained unclear, however. We here determined the frequency of T790M acquisition at diagnosis of progressive disease in patients with EGFR-mutated non-small cell lung cancer (NSCLC) treated with afatinib as first-line EGFR-TKI...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28743421/a-review-of-regimens-combining-pemetrexed-with-an-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-in-the-treatment-of-advanced-nonsquamous-non-small-cell-lung-cancer
#11
REVIEW
James Chih-Hsin Yang, Tony Mok, Baohui Han, Mauro Orlando, Tarun Puri, Keunchil Park
Pemetrexed is a standard first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC), and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a standard first-line treatment for advanced nonsquamous NSCLC with activating EGFR mutations. Pemetrexed and EGFR TKIs have different mechanisms of action and minimally overlapping toxicity profiles; therefore, it is hypothesized that their combination might result in acceptable toxicity, provided that the synergistic antitumor activity observed in preclinical studies is achieved...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28742791/correlation-between-circulating-tumor-dna-levels-and-response-to-tyrosine-kinase-inhibitors-tki-treatment-in-non-small-cell-lung-cancer
#12
Zhangjing Wei, Wenyue Wang, Zitan Shu, Xue Zhou, Yanfang Zhang
BACKGROUND Clinical monitoring of EGFR-positive NSCLC patients is important to gauge treatment response. The current study addresses the usage of circulating tumor DNA (ctDNA) as a prognostic marker during treatment of first-generation TKIs. MATERIAL AND METHODS Serial samplings of peripheral blood from 200 EGFR-positive NSCLC patients were taken. Baseline ctDNA quantification was conducted by digital droplet PCR before TKI treatment was administered and compared to primary biopsies. Thereafter blood sampling at different treatment cycles were measured and assessed for its prognostic and predictive value...
July 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
August 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
#19
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 31, 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
#20
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...
September 2017: Clinical Neurology and Neurosurgery
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