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Brain metastases lung cancer tki

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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
#1
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
#2
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...
October 23, 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
#3
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
#4
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
#5
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
#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)...
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
#7
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
#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...
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28391386/assessment-of-prognostic-scores-of-brain-metastases-from-lung-adenocarcinoma-with-egfr-mutations
#16
Hongwei Li, Jianhong Lian, Hongxing Jin, Weili Wang, Jianzhong Cao, Xiaqin Zhang, Xin Song, Sufang Jia, Haixia Jia, Jiwei Ren, Songyan Han, Weihua Yang, Yanfeng Xi, Shengmin Lan
The aim of this study was to analyze prognostic factors and evaluate the value of four prognostic scores including RPA, DS-GPA BS-BM, GGS for the EGFR mutant BM patients from lung adenocarcinoma treated with EGFR-TKI. Data of NSCLC were retrospectively reviewed from August 2010 to June 2015 using the medical database of Shanxi Provincial Cancer Hospital. Patients with BM from lung adenocarcinoma with mutant EGFR treated by EGFR-TKI or a combination of EGFR-TKI and WBRT were included. Potential prognostic factors were statistically examined...
May 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28376735/central-nervous-system-progression-in-advanced-non-small-cell-lung-cancer-patients-with-egfr-mutations-in-response-to-first-line-treatment-with-two-egfr-tkis-gefitinib-and-erlotinib-a-comparative-study
#17
Meng-Xia Li, Hao He, Zhi-Hua Ruan, Yu-Xi Zhu, Rong-Qing Li, Xiao He, Bao-Hua Lan, Zhi-Min Zhang, Guo-Dong Liu, Hua-Liang Xiao, Yan Wu, Bo Zhu, Ge Wang, Zhen-Zhou Yang
BACKGROUND: Central nervous system (CNS) brain metastasis of advanced non-small cell lung cancer (NSCLC) patients confers a worse quality of life and prognosis. The efficacy comparison of two first-generation epidermal growth factor receptor (EGFR) inhibitors erlotinib or gefitinib as first-line treatment for CNS metastasis NSCLC patients with EGFR-sensitizing mutations is yet to be elucidated. METHODS: A retrospective analysis was done on cerebral metastasis rate after erlotinib or gefitinib as first-line treatment for advanced NSCLC patients with EGFR-sensitizing mutations...
April 4, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28363487/treatment-options-for-patients-with-brain-metastases-from-egfr-alk-driven-lung-cancer
#18
Mark K Doherty, Grzegorz J Korpanty, Pascale Tomasini, Moein Alizadeh, Kevin Jao, Catherine Labbé, Celine M Mascaux, Petra Martin, Suzanne Kamel-Reid, Ming-Sound Tsao, Melania Pintilie, Geoffrey Liu, Penelope A Bradbury, Ronald Feld, Natasha B Leighl, Caroline Chung, Frances A Shepherd
INTRODUCTION: Brain metastases in EGFR/ALK-driven NSCLC frequently pose treatment dilemmas. Tyrosine kinase inhibitors (TKIs) can control extracranial disease, but radiotherapy is often required for intracranial control. We aimed to evaluate the impact of first-line whole brain radiotherapy (WBRT), stereotactic radiotherapy (SRS) or TKI alone on outcomes of patients with brain metastases from EGFR/ALK-driven NSCLC. METHODS: This single center retrospective review included 184 patients with brain metastases from EGFR/ALK-driven NSCLC, and analyzed effect of treatment choice on time to intracranial progression (TTIP) and overall survival (OS)...
May 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28341106/the-apple-trial-feasibility-and-activity-of-azd9291-osimertinib-treatment-on-positive-plasma-t790m-in-egfr-mutant-nsclc-patients-eortc-1613
#19
Jordi Remon, Jessica Menis, Baktiar Hasan, Aleksandra Peric, Eleonora De Maio, Silvia Novello, Martin Reck, Thierry Berghmans, Bartosz Wasag, Benjamin Besse, Rafal Dziadziuszko
The AZD9291 (Osimertinib) Treatment on Positive PLasma T790M in EGFR-mutant NSCLC Patients (APPLE) trial is a randomized, open-label, multicenter, 3-arm, phase II study in advanced, epidermal growth factor receptor (EGFR)-mutant and EGFR tyrosine kinase inhibitor (TKI)-naive non-small-cell lung cancer (NSCLC) patients, to evaluate the best strategy for sequencing gefitinib and osimertinib treatment. Advanced EGFR-mutant NSCLC patients, with World Health Organization performance status 0-2 who are EGFR TKI treatment-naive and eligible to receive first-line treatment with EGFR TKI will be randomized to: In all arms, a plasmatic ctDNA T790M test will be performed by a central laboratory at the Medical University of Gdansk (Poland) but will be applied as a predictive marker for making treatment decisions only in arm B...
March 1, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28216278/outcomes-of-patients-with-metastatic-renal-cell-carcinoma-and-bone-metastases-in-the-targeted-therapy-era
#20
Sarathi Kalra, Jonathan Verma, Bradley J Atkinson, Surena F Matin, Christopher G Wood, Jose A Karam, Sue-Hwa Lin, Robert L Satcher, Pheroze Tamboli, Kanishka Sircar, Priya Rao, Paul G Corn, Nizar M Tannir, Eric Jonasch
BACKGROUND: Bone metastases (BMs) occur commonly in patients with metastatic renal cell carcinoma (mRCC). Tyrosine kinase inhibitors (TKIs) have improved the outcomes for patients with mRCC. However, data on the outcomes of mRCC patients with BMs treated with TKIs are limited. We describe the outcomes of patients with BMs treated with TKI therapy and compare them with the outcomes from a pre-TKI group. PATIENTS AND METHODS: Using an institutional tumor registry, a retrospective review of patients with mRCC from 2002 to 2003 and 2006 to 2007 was performed...
January 18, 2017: Clinical Genitourinary Cancer
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