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Brain metastases lung cancer tki

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https://www.readbyqxmd.com/read/29722340/role-of-recursive-partitioning-analysis-and-graded-prognostic-assessment-on-identifying-non-small-cell-lung-cancer-patients-with-brain-metastases-who-may-benefit-from-postradiation-systemic-therapy
#1
Shuai Liu, Peng Chen, Yan-Wei Liu, Xue-Nan Gu, Xiao-Guang Qiu, Bo Li
Background: The role of postradiation systemic therapy in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) was controversial. Thus, we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) and graded prognostic assessment (GPA) in identifying population who may benefit from postradiation systemic therapy. Methods: The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively...
May 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29713183/multiple-treatment-modalities-for-brain-metastasis-in-patients-with-egfr-mutant-non-small-cell-lung-cancer
#2
Haiyang Wang, Xiaoqing Yu, Yun Fan, Youhua Jiang
Background: There are many controversies concerning the best management of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients with brain metastases (BMs). The use of upfront EGFR tyrosine kinase inhibitors (TKIs) and the withholding of local therapies or upfront radiation therapies (RTs) remain controversial. Available treatment options include local therapies such as whole-brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) and surgery, EGFR-TKIs, and chemotherapy...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29696132/brain-metastases-in-oncogene-addicted-non-small-cell-lung-cancer-patients-incidence-and-treatment
#3
REVIEW
J Remon, Benjamin Besse
Brain metastases (BM) are common in non-small cell lung cancer patients including in molecularly selected populations, such as EGFR -mutant and ALK -rearranged tumors. They are associated with a reduced quality of life, and are commonly the first site of progression for patients receiving tyrosine kinase inhibitors (TKIs). In this review, we summarize incidence of BM and intracranial efficacy with TKI agents according to oncogene driver mutations, focusing on important clinical issues, notably optimal first-line treatment in oncogene-addicted lung tumors with upfront BM (local therapies followed by TKI vs...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29656746/impacts-of-egfr-mutation-status-and-egfr-tki-on-the-efficacy-of-stereotactic-radiosurgery-for-brain-metastases-from-non-small-cell-lung-adenocarcinoma-a-retrospective-analysis-of-133-consecutive-patients
#4
Shoji Yomo, Kyota Oda
OBJECTIVES: Recent advances in target therapies have prolonged overall survival (OS) for patients with epidermal growth factor receptor (EGFR)-mutant lung cancer. The impact of EGFR mutations on stereotactic radiosurgery (SRS) for brain metastases (BM) has yet to be determined. The present study sought to evaluate the efficacy and limitations of SRS, administered with EGFR-tyrosine kinase inhibitors (TKI), for BM from EGFR-mutant lung adenocarcinoma. MATERIALS AND METHODS: This retrospective observational study analyzed data from patients with BM arising from EGFR-mutant lung adenocarcinoma who received upfront Gamma Knife SRS between December 2010 and April 2016...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29650684/epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-for-central-nervous-system-metastases-from-non-small-cell-lung-cancer
#5
REVIEW
Manmeet S Ahluwalia, Kevin Becker, Benjamin P Levy
Central nervous system (CNS) metastases are a common complication in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), resulting in a poor prognosis and limited treatment options. Treatment of CNS metastases requires a multidisciplinary approach, and the optimal treatment options and sequence of therapies are yet to be established. Many systemic therapies have poor efficacy in the CNS due to the challenges of crossing the blood-brain barrier (BBB), creating a major unmet need for the development of agents with good BBB-penetrating biopharmaceutical properties...
April 12, 2018: Oncologist
https://www.readbyqxmd.com/read/29644484/intracranial-control-and-survival-outcome-of-tyrosine-kinase-inhibitor-tki-alone-versus-tki-plus-radiotherapy-for-brain-metastasis-of-epidermal-growth-factor-receptor-mutant-non-small-cell-lung-cancer
#6
SooYoon Sung, Sea-Won Lee, Yoo-Kang Kwak, Jin Hyung Kang, Sook Hee Hong, Yeon-Sil Kim
INTRODUCTION: The efficacy of tyrosine kinase inhibitors (TKIs) with and without radiotherapy (RT) has not been determined in patients with brain metastases from epidermal growth factor receptor-mutant TKI naïve non-small cell lung cancer (NSCLC). METHODS: Between 2008 and 2016, 586 patients were diagnosed with NSCLC and treated with TKIs at a hospital in Seoul, South Korea; 81 of these patients met the eligibility criteria for our study. Outcomes analyzed included intracranial progression (ICP), neurological death, and overall survival (OS)...
April 11, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29563138/ensartinib-x-396-in-alk-positive-non-small-cell-lung-cancer-results-from-a-first-in-human-phase-i-ii-multicenter-study
#7
Leora Horn, Jeffrey R Infante, Karen L Reckamp, George R Blumenshein, Ticiana A Leal, Saiama N Waqar, Barbara J Gitlitz, Rachel E Sanborn, Jennifer G Whisenant, Liping Du, Joel W Neal, Jon P Gockerman, Gary Dukart, Kimberly Harrow, Chris Liang, James J Gibbons, Allison Holzhausen, Christine M Lovly, Heather A Wakelee
PURPOSE: Evaluate safety and determine the recommended phase II dose (RP2D) of ensartinib (X-396), a potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), and evaluate preliminary pharmacokinetics and antitumor activity in a first-in-human, phase I/II clinical trial primarily in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: In dose escalation, ensartinib was administered at doses of 25-250 mg once daily in patients with advanced solid tumors; in dose expansion, patients with advanced ALK-positive NSCLC were administered 225 mg once daily...
March 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29507851/non-small-cell-lung-cancer-with-multiple-brain-metastases-treated-with-radiosurgery-and-erlotinib-a-case-report
#8
Bilgehan Sahin, Teuta Mustafayev, Gokhan Aydin, Gorkem Gungor, Bulend Yapici, Banu Atalar, Enis Ozyar
Brain metastases are commonly seen complications in non-small cell lung cancer (NSCLC) patients. The incidence of brain metastases is increasing as a result of more effective systemic targeted therapies with prolonged survival. The prognosis is usually poor, and up to six months of median survivals were reported with different therapeutic options. Here, we present an NSCLC case with multiple brain metastases treated with radiosurgery and systemic erlotinib therapy with prolonged survival. The use of tyrosine kinase inhibitors (TKI) in conjunction with either stereotactic radiosurgery or whole brain radiotherapy is not well established in terms of efficiency and toxicity...
December 29, 2017: Curēus
https://www.readbyqxmd.com/read/29354805/current-progress-and-outcomes-of-clinical-trials-on-using-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-therapy-in-non-small-cell-lung-cancer-patients-with-brain-metastases
#9
Ling-Ling Kong, Lin-Lin Wang, Li-Gang Xing, Jin-Ming Yu
Non-small cell lung cancer (NSCLC) continues to be one of the major causes of cancer-related deaths worldwide, and brain metastases are the major cause of death in NSCLC patients. With recent advances in understanding the underlying molecular mechanism of NSCLC development and progression, mutations in epidermal growth factor receptor ( EGFR ) have been recognized as a key predictor of therapeutic sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Using EGFR-TKI alone or in combination with standard treatments such as whole-brain radiotherapy and surgery has been an effective strategy for the management of brain metastasis...
December 2017: Chronic diseases and translational medicine
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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...
February 2018: 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
#16
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
#17
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...
February 2018: 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
#18
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
#19
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
#20
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
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