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Brain metastases lung cancer tki

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https://www.readbyqxmd.com/read/29340055/concurrent-brain-radiotherapy-and-egfr-tki-may-improve-intracranial-metastases-control-in-non-small-cell-lung-cancer-and-have-survival-benefit-in-patients-with-low-ds-gpa-score
#1
Yongmei Liu, Lei Deng, Xiaojuan Zhou, Youling Gong, Yong Xu, Lin Zhou, Jin Wan, Bingwen Zou, Yongsheng Wang, Jiang Zhu, Zhenyu Ding, Feng Peng, Meijuan Huang, Li Ren, Tim Lautenschlaeger, Feng-Ming Spring Kong, You Lu
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has intracranial activity in EGFR-mutant Non-Small Cell Lung Cancer (NSCLC). The optimal timing of brain radiotherapy (RT) and appropriate patients who need early brain RT remains undetermined. This is a retrospective study of EGFR-mutant NSCLC patients with newly diagnosed brain metastases (BMs) before EGFR-TKI initiation. Intra-cranial progression free survival (IC-PFS) and overall survival (OS) were measured from the date of EGFR-TKI treatment...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29336166/optimizing-outcomes-in-egfr-mutation-positive-nsclc-which-tyrosine-kinase-inhibitor-and-when
#2
Nicolas Girard
Despite the efficacy of standard-of-care EGFR tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib and afatinib, in EGFR mutation-positive non-small-cell lung cancer, resistance develops, most commonly due to the T790M mutation. Osimertinib showed clinical activity in the treatment of T790M-positive disease following progression on a first-line TKI, and is approved in this setting. Recently, osimertinib improved efficacy versus first-generation TKIs (erlotinib and gefitinib) in the first-line setting. Multiple factors can influence first-line treatment decisions, including subsequent therapy options, presence of brain metastases and tolerability, all of which should be considered in the long-term treatment plan...
January 16, 2018: Future Oncology
https://www.readbyqxmd.com/read/29290255/egfr-rad51-fusion-variant-in-lung-adenocarcinoma-and-response-to-erlotinib-a-case-report
#3
You-Cai Zhu, Wen-Xian Wang, Chun-Wei Xu, Zheng-Bo Song, Kai-Qi Du, Gang Chen, Tang-Feng Lv, Yong Song
The most frequent epidermal growth factor receptor (EGFR) mutations of lung cancer include exon 19 in deletion and the exon 21 L858R mutation. And EGFR-tyrosine kinase inhibitor (TKI) as the standard first line treatment show good response to classical/sensitizing EGFR mutations. With the development of detection methods, some uncommon genomic mutation events such as exon 18-25 kinase domain duplications (KDD) and EGFR rearrangements (EGFR-RAD51 or EGFR-PURB) are found. We reported a case of EGFR-RAD51 fusion in non-small-cell lung cancer(NSCLC) and the efficacy of erlotinib to this type fusion of NSCLC patients...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29172778/response-to-afatinib-in-treatment-na%C3%A3-ve-patients-with-advanced-mutant-epidermal-growth-factor-receptor-lung-adenocarcinoma-with-brain-metastases
#4
COMPARATIVE STUDY
Shih-Hong Li, Chien-Ying Liu, Ping-Chih Hsu, Yueh-Fu Fang, Chun-Chieh Wang, Kuo-Chin Kao, Li-Chuan Tseng, Cheng-Ta Yang
BACKGROUND: Brain metastases are observable in 20-40% of non-small cell lung cancer patients, but standard treatments for such metastases may be intolerable to some. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were found to be effective against mutant-EGFR lung adenocarcinomas, but data regarding their effectiveness, especially for the second-generation EGFR-TKI afatinib, is limited. This study compared key outcomes for afatanib monotherapy versus afatinib combined with whole-brain radiotherapy (WBRT) in treatment-naïve lung adenocarcinoma patients harboring EGFR mutations...
January 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29151955/continuation-of-tyrosine-kinase-inhibitor-is-associated-with-survival-benefit-in-nsclc-patients-with-exon-19-deletion-after-solitary-progression
#5
Feifei Na, Jie Zhang, Lei Deng, Xiaojuan Zhou, Lin Zhou, Bingwen Zou, Min Yu, Yanying Li, Jianxin Xue, Yongmei Liu
INTRODUCTION: The benefit and selection criteria of continuing tyrosine kinase inhibitor (TKI) after secondary resistance in non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutation remain largely unknown. This study was designed to investigate the role and predictive factors of TKI continuation in patients with solitary progression. METHODS: We retrospectively analyzed NSCLCs treated with first generation of TKI from June 2009 to October 2014 in our cancer center...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29111173/epidermal-growth-factor-receptor-mutation-predicts-favorable-outcomes-in-non-small-cell-lung-cancer-patients-with-brain-metastases-treated-with-stereotactic-radiosurgery
#6
Wen-Chi Yang, Furen Xiao, Jin-Yuan Shih, Chao-Chi Ho, Ya-Fang Chen, Ham-Min Tseng, Kuan-Yu Chen, Wei-Yu Liao, Chong-Jen Yu, James Chih-Hsin Yang, Sung-Hsin Kuo, Jason Chia-Hsien Cheng, Pan-Chyr Yang, Feng-Ming Hsu
PURPOSE: The impact of epidermal growth factor receptor (EGFR) mutations on radiotherapy for brain metastases (BM) is undetermined. We evaluated the effects of EGFR mutation status on responses and outcomes in non-small cell lung cancer (NSCLC) patients with BM, treated with upfront or salvage stereotactic radiosurgery (SRS). METHODS AND MATERIALS: From 2008 to 2015, 147 eligible NSCLC patients with 300 lesions were retrospectively analyzed. Patterns of tyrosine kinase inhibitor (TKI) therapy were recorded...
October 27, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29074098/lorlatinib-in-non-small-cell-lung-cancer-with-alk-or-ros1-rearrangement-an-international-multicentre-open-label-single-arm-first-in-man-phase-1-trial
#7
MULTICENTER STUDY
Alice T Shaw, Enriqueta Felip, Todd M Bauer, Benjamin Besse, Alejandro Navarro, Sophie Postel-Vinay, Justin F Gainor, Melissa Johnson, Jorg Dietrich, Leonard P James, Jill S Clancy, Joseph Chen, Jean-François Martini, Antonello Abbattista, Benjamin J Solomon
BACKGROUND: Most patients with anaplastic lymphoma kinase (ALK)-rearranged or ROS proto-oncogene 1 (ROS1)-rearranged non-small-cell lung cancer (NSCLC) are sensitive to tyrosine kinase inhibitor (TKI) therapy, but resistance invariably develops, commonly within the CNS. This study aimed to analyse the safety, efficacy, and pharmacokinetic properties of lorlatinib, a novel, highly potent, selective, and brain-penetrant ALK and ROS1 TKI with preclinical activity against most known resistance mutations, in patients with advanced ALK-positive or ROS1-positive NSCLC...
December 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29041833/healthcare-costs-in-patients-with-advanced-non-small-cell-lung-cancer-and-disease-progression-during-targeted-therapy-a-real-world-observational-study
#8
Karen E Skinner, Ancilla W Fernandes, Mark S Walker, Melissa Pavilack, Ari VanderWalde
AIMS: To assess healthcare costs during treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and following disease progression in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis of medical records of US community oncology practices was conducted. Eligible patients had advanced NSCLC (stage IIIB/IV) diagnosed between January 1, 2008 and January 1, 2015, initiated treatment with erlotinib or afatinib (first-line or second-line), and had disease progression...
October 18, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28979145/anaplastic-lymphoma-kinase-inhibition-in-metastatic-non-small-cell-lung-cancer-clinical-impact-of-alectinib
#9
REVIEW
Ittai B Muller, Adrianus J de Langen, Elisa Giovannetti, Godefridus J Peters
A subset of non-small cell lung cancer (NSCLC) tumors (5%) harbors an anaplastic lymphoma kinase (ALK) translocation that drives tumorigenesis. The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS) in treated and untreated patients by 4 months compared to standard chemotherapy. While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28961841/dual-met-and-erbb-inhibition-overcomes-intratumor-plasticity-in-osimertinib-resistant-advanced-non-small-cell-lung-cancer-nsclc
#10
A Martinez-Marti, E Felip, J Matito, E Mereu, A Navarro, S Cedrés, N Pardo, A Martinez de Castro, J Remon, J M Miquel, A Guillaumet-Adkins, E Nadal, G Rodriguez-Esteban, O Arqués, R Fasani, P Nuciforo, H Heyn, A Villanueva, H G Palmer, A Vivancos
Background: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib are the last line of targeted treatment of metastatic non-small-cell lung cancer (NSCLC) EGFR-mutant harboring T790M. Different mechanisms of acquired resistance to third-generation EGFR-TKIs have been proposed. It is therefore crucial to identify new and effective strategies to overcome successive acquired mechanisms of resistance. Methods: For Amplicon-seq analysis, samples from the index patient (primary and metastasis lesions at different timepoints) as well as the patient-derived orthotopic xenograft tumors corresponding to the different treatment arms were used...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical 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
#11
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)...
November 2017: Journal of Medical Economics
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
#12
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...
September 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28704781/impacts-of-egfr-mutation-and-egfr-tkis-on-incidence-of-brain-metastases-in-advanced-non-squamous-nsclc
#13
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
https://www.readbyqxmd.com/read/28667686/pulsatile-crizotinib-treatment-for-brain-metastasis-in-a-patient-with-non-small-cell-lung-cancer
#14
S Wang, J Chen, Z Xie, L Xia, W Luo, J Li, Q Li, Z Yang
WHAT IS KNOWN AND OBJECTIVE: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is a distinct subtype with patients showing peculiar clinicopathological features and dramatic responses to the ALK tyrosine kinase inhibitor crizotinib. Patients with this cancer variant have a dismal prognosis and limited treatment options when it has progressed to intracranial metastasis because of inadequate drug penetration into the central nervous system (CNS). Factors associated with response to TKI therapy have been reported to include pharmacokinetic and biodynamic resistance phenomena...
June 30, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28565936/osimertinib-a-third-generation-tyrosine-kinase-inhibitor-for-treatment-of-epidermal-growth-factor-receptor-mutated-non-small-cell-lung-cancer-with-the-acquired-thr790met-mutation
#15
Meredith K Bollinger, Amanda S Agnew, Gerard P Mascara
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for the treatment of metastatic EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) in patients failing previous TKI therapy. The T790M mutation is an acquired resistance mechanism found in over half of patients with NSCLC progressing on first-generation TKIs. First- and second-generation TKIs do not inhibit the T790M mutation at clinically relevant concentrations. Osimertinib is selective for mutated forms of EGFR, including the TKI-sensitizing mutations L858R and exon 19 deletions, as well as the acquired T790M resistance mutation...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28555261/paradigm-shift-of-therapeutic-management-of-brain-metastases-in-egfr-mutant-non-small-cell-lung-cancer-in-the-era-of-targeted-therapy
#16
REVIEW
Akimasa Sekine, Hiroaki Satoh
Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations commonly present brain metastases (BM) at the time of NSCLC diagnosis or during the clinical course. Conventionally, the prognosis of BM has been extremely poor, but the advent of EGFR-tyrosine kinase inhibitors (TKIs) has drastically improved the prognosis in these patients. Despite the presence of the blood-brain barrier, EGFR-TKIs have dramatic therapeutic effects on both BM and extracranial disease. In addition, recent systemic chemotherapies reportedly play a role in controlling BM...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28540256/concurrent-afatinib-and-whole-brain-radiotherapy-in-exon-19-del-egfr-mutant-lung-adenocarcinoma-a-case-report-and-mini-review-of-the-literature
#17
Chukwuka Eze, Nina-Sophie Hegemann, Olarn Roengvoraphoj, Maurice Dantes, Farkhad Manapov
Leptomeningeal metastases (LM) are found in approximately 3.8% of non-small cell lung cancer cases with an increased incidence in adenocarcinoma, and approximately one-third of patients will present with concomitant brain metastases. We report the case of a 50-year-old male patient with stage IV exon 19-del-EGFR mutant lung adenocarcinoma who progressed on second-generation TKI therapy with manifestation of symptomatic simultaneous diffuse brain and LM. Whole-brain radiotherapy with concurrent afatinib resulted in an almost complete regression of neurological symptoms as well as good, durable radiological response...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28454365/downregulation-of-egfr-in-a-metastatic-brain-lesion-of-egfr-mutated-non-small-cell-lung-cancer-using-a-tyrosine-kinase-inhibitor-a-case-report
#18
Masatoshi Takagaki, Manabu Kinoshita, Kazumi Nishino, Masakazu Nakano, Hiroko Adachi, Morio Ueno, Masanori Kitamura, Yasunori Fujimoto, Kei Tashiro, Yasuhiko Tomita, Fumio Imamura, Toshiki Yoshimine
Brain metastasis is a common complication in patients with cancer, with lung cancer being the most frequent origin of brain metastases. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have begun to serve a pivotal role in lung cancer treatment and have been reported to demonstrate anticancer activity against brain metastases by penetrating the blood-brain barrier. The present study reports, to the best of our knowledge, the first case of EGFR-mutated non-small cell lung cancer (NSCLC) brain metastasis that was surgically resected while the lesion was responding to the EGFR-TKI erlotinib...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28412028/-effectiveness-of-erlotinib-in-critical-care-unit-in-patients-with-non-small-cell-lung-cancer-with-egfr-mutation
#19
M Dewolf, C Dayen, C Garoute, W Khamis, M Fourrier, F Rousselle, M Sadki, F Le Meunier, R Suguenot, E Lecuyer, H Bentayeb, Y Douadi, P Berna
INTRODUCTION: The search for mutations epidermal growth factor receptor (EGFR) has changed the therapeutic approach and prognosis of non-small cell lung cancer (NSCLC). The effectiveness of tyrosine kinase inhibitors (TKI) has been demonstrated orally in patients with EGFR mutation. We report the case of a patient for whom treatment with TKI was started effectively in a Critical Care Unit. OBSERVATION: A patient of 59 years is followed for a stage IV lung adenocarcinoma with metastases in liver, brain, adrenal, lung and pleura...
June 2017: Revue de Pneumologie Clinique
https://www.readbyqxmd.com/read/28391420/a-neuro-oncologist-s-perspective-on-management-of-brain-metastases-in-patients-with-egfr-mutant-non-small-cell-lung-cancer
#20
REVIEW
Tresa McGranahan, Seema Nagpal
Management of non-small cell lung cancer (NSCLC) with brain metastasis (BrM) has been revolutionized by identification of molecular subsets that have targetable oncogenes. Historically, survival for NSCLC with symptomatic BrM was weeks to months. Now, many patients are surviving years with limited data to guide treatment decisions. Tumors with activating mutations in epidermal growth factor receptor (EGFRact+) have a higher incidence of BrM, but a longer overall survival. The high response rate of both systemic and BrM EGFRact+ NSCLC to tyrosine kinase inhibitors (TKIs) has led to the rapid incorporation of new therapies but is outpacing evidence-based decisions for BrM in NSCLC...
April 2017: Current Treatment Options in Oncology
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