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New era of epidermal growth factor receptor-tyrosine kinase inhibitors for lung cancer
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作者 Joana Espiga Macedo 《World Journal of Respirology》 2016年第2期57-62,共6页
Lung cancer is the leading cause of death globally, besides recent advances in its management; it maintains a low 5-year survival rate of 15%. The discovery of epidermal growth factor receptor(EGFR) activating mutatio... Lung cancer is the leading cause of death globally, besides recent advances in its management; it maintains a low 5-year survival rate of 15%. The discovery of epidermal growth factor receptor(EGFR) activating mutations and the introduction of its tyrosine kinase inhibitors(TKIs) have expanded the treatment options for patients with non-small cell lung cancer. Nowadays, EGFR mutation testing is now a common routine for newly diagnosed lung cancer. First generation TKIs developed, erlotinib and gefitinib, were reversible ones. After a median of 14 mo, eventually all EGFR mutated patients develop resistance to reversible TKIs. Afatinib, dacomitinib and neratinib, second generation inhibitors, are selective and irreversible TKIs. Finally, third generation phase Ⅰclinical trials were performed, with lower toxicity profiles, and targeting with more precision the driving clone of this heterogeneous disease. 展开更多
关键词 EPIDERMAL growth factor receptor-tyrosine kinase inhibitors CLONAL evolution NON-SMALL cell lung cancer ACQUIRED resistance
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Clinical Benefit of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors Plus Radiotherapy for Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer: A Retrospective Analysis on Real World Data 被引量:2
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作者 Wang Ranlin Li Tao +2 位作者 Lv Jiahua Sun Chang Shi Qiuling 《肿瘤预防与治疗》 2019年第5期385-394,共10页
Objective: To investigate the benefit of epidermal growth factor receptor( EGFR) tyrosine kinase inhibitors( TKIs)with radiotherapy in patients with EGFR mutation-positive metastatic non-small cell lung cancer( NSCLC)... Objective: To investigate the benefit of epidermal growth factor receptor( EGFR) tyrosine kinase inhibitors( TKIs)with radiotherapy in patients with EGFR mutation-positive metastatic non-small cell lung cancer( NSCLC),compared with TKIs alone.Methods: A total of 103 patients with stage Ⅳ EGFR-mutated NSCLC treated from February 2015 to May 2017 at Sichuan Cancer Hospital were analyzed retrospectively. Fifty patients were treated with EGFR-TKIs( gefitinib or erlotinib) plus radiotherapy( the TKI +RT group) and 53 patients received EGFR-TKIs alone( the TKI group). Tumor response,survival and toxicities were compared between the two groups. Results: Median follow-up time was 11. 7 months( 2. 8-36. 3 months). The overall response rate( ORR) and disease control rate( DCR) in the TKI + RT group vs the TKI group were 62% vs 37. 7%( P = 0. 014) and 88% vs 75. 5%( P =0. 101),respectively. The median progression-free survival( PFS) and median overall survival( OS) in the TKI + RT group were superior to those of the TKI group( 18. 87 months vs 12. 80 months,P = 0. 035 and 23. 10 months vs 18. 30 months,P = 0. 011). OS rates in the TKI + RT group and the TKI group were 56. 0% vs 35. 8% at year 1( P = 0. 04) and 16. 0% vs 3. 8% at year 2( P =0. 036). Multivariate Cox model found that TKI + RT related to significantly better OS( hazard ratio = 0. 209;95% CI,0. 066 to0. 661;P = 0. 008) than TKI alone. Adverse events did not differ significantly between the two groups( P > 0. 050). Conclusion:Compared with EGFR-TKIs alone,EGFR-TKIs combined with radiotherapy was well tolerated and showed benefit in tumor response and survival for EGFR mutation-positive metastatic NSCLC patients. 展开更多
关键词 RADIOTHERAPY NON-SMALL cell lung cancer EPIDERMAL growth factor receptor-tyrosine kinase inhibitor Effectiveness
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Plasma relative abundance of epidermal growth factor receptor mutations predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced lung adenocarcinoma
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作者 徐含烟 《China Medical Abstracts(Internal Medicine)》 2019年第2期103-104,共2页
Objective To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in... Objective To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced lung adenocarcinoma. Methods In this prospective study,adult patients with advanced lung adenocarcinoma were enrolled in our hospital from 1 April 2016 to 1 January 2017. EGFR mutations in tumortissues were detected by ADx-amplification refractory mutationsystem (ADx-ARMS). EGFR mutations of plasmafree tumor DNA were detected by ADx-ARMS and ADxsuperamplification refractory mutation system (ADx-SuperARMS)at the same time. Patients with EGFR-mutantin tumor tissues and receiving EGFR-TKIs were finallyenrolled. Plasma mutation-positive patients with bothmethods were high abundance group. Patients with positivemutations by ADx-SuperARMS but negative of ADx-ARMS were medium abundance group. 展开更多
关键词 PFS PLASMA relative abundance of EPIDERMAL growth factor RECEPTOR mutations predicts clinical response to EPIDERMAL growth factor receptor-tyrosine kinase inhibitors in PATIENTS with advanced lung adenocarcinoma
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HER3-targeted therapeutic antibodies and antibody-drug conjugates in non-small cell lung cancer refractory to EGFR-tyrosine kinase inhibitors
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作者 Margaret E.Larsen Hui Lyu Bolin Liu 《Chinese Medical Journal Pulmonary and Critical Care Medicine》 2023年第1期11-17,共7页
Human epidermal growth factor receptor 3(HER3)is a unique member of the human epidermal growth factor receptor(HER/EGFR)family,since it has negligible kinase activity.Therefore,HER3 must interact with a kinase-profici... Human epidermal growth factor receptor 3(HER3)is a unique member of the human epidermal growth factor receptor(HER/EGFR)family,since it has negligible kinase activity.Therefore,HER3 must interact with a kinase-proficient receptor to form a heterodimer,leading to the activation of signaling cascades.Overexpression of HER3 is observed in various human cancers,including non-small cell lung cancer(NSCLC),and correlates with poor clinical outcomes in patients.Studies on the underlying mechanism demonstrate that HER3-initiated signaling promotes tumor metastasis and causes treatment failure in human cancers.Upregulation of HER3 is frequently observed in EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors(TKIs).Increased expression of HER3 triggers the so-called EGFR-independent mechanism via interactions with other receptors to activate“by-pass signaling pathways”,thereby resulting in resistance to EGFR-TKIs.To date,no HER3-targeted therapy has been approved for cancer treatment.In both preclinical and clinical studies,targeting HER3 with a blocking an-tibody(Ab)is the only strategy being examined.Recent evaluations of an anti-HER3 Ab-drug conjugate(ADC)show promising results in patients with EGFR-TKI-resistant NSCLC.Herein,we summarize our understanding of the unique biology of HER3 in NSCLC refractory to EGFR-TKIs,with a focus on its dimerization partners and subsequent activation of signaling pathways.We also discuss the latest development of the therapeutic Abs and ADCs targeting HER3 to abrogate EGFR-TKI resistance in NSCLC. 展开更多
关键词 Human epidermal growth factor receptor 3(HER3) Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKI) Resistance ANTIBODY Antibody-drug conjugate(ADC) Non-small cell lung cancer(NSCLC)
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盐酸埃克替尼的药理学及临床研究进展 被引量:10
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作者 王雷 于佩瑶 刘基巍 《临床肿瘤学杂志》 CAS 2014年第3期274-279,共6页
非小细胞肺癌( NSCLC)约占肺癌的80%~85%。晚期NSCLC主要以内科治疗为主,既往主要应用化疗,但疗效差。近年来,表皮生长因子受体酪氨酸激酶抑制剂( EGFR-TKI)的应用为NSCLC的治疗提出了新的突破。盐酸埃克替尼作为一种国产的EG... 非小细胞肺癌( NSCLC)约占肺癌的80%~85%。晚期NSCLC主要以内科治疗为主,既往主要应用化疗,但疗效差。近年来,表皮生长因子受体酪氨酸激酶抑制剂( EGFR-TKI)的应用为NSCLC的治疗提出了新的突破。盐酸埃克替尼作为一种国产的EGFR-TKI,其临床前期研究及其临床研究均显示其较好的安全性、耐受性和疗效,为晚期NSCLC治疗的新选择。 展开更多
关键词 表皮生长因子受体酪氨酸激酶抑制剂 盐酸埃克替尼 药代动力学 临床试验 EPIDERMAL growth factor receptor-tyrosine kinase inhibitor( EGFR-TKI)
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非小细胞肺癌脑转移药物治疗的研究进展 被引量:5
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作者 蔡忠福 欧阳学农 余宗阳 《临床肿瘤学杂志》 CAS 2014年第4期379-382,共4页
非小细胞肺癌( NSCLC)是最常见的恶性肿瘤之一,也是导致癌症死亡的主要原因,其疗效欠佳、预后差,尤其是伴有脑转移患者。 NSCLC伴脑转移患者生活质量差,预后不良,自然中位生存期仅为1~2个月,全脑放射治疗虽然在一定程度上改善... 非小细胞肺癌( NSCLC)是最常见的恶性肿瘤之一,也是导致癌症死亡的主要原因,其疗效欠佳、预后差,尤其是伴有脑转移患者。 NSCLC伴脑转移患者生活质量差,预后不良,自然中位生存期仅为1~2个月,全脑放射治疗虽然在一定程度上改善了患者的生活质量,延长了患者的生存期,但疗效仍不理想。近年来围绕培美曲塞、替莫唑胺以及表皮生长因子受体酪氨酸激酶抑制剂( EGFR-TKIs)开展了一些研究,并取得了一定的成果。本文就针对培美曲塞、替莫唑胺及EGFR-TKIs等抗肿瘤药物在NSCLC伴脑转移中的研究进展进行综述。 展开更多
关键词 非小细胞肺癌 脑转移 细胞毒药物 表皮生长因子受体酪氨酸激酶抑制剂 NON-SMALL cell lung cancer (NSCLC) EPIDERMAL growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)
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槐定碱对神经胶质瘤U87细胞增殖、侵袭及相关信号通路的影响 被引量:10
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作者 赵树鹏 靳彩玲 +3 位作者 高国军 赵新利 金保哲 周文科 《中国肿瘤生物治疗杂志》 CAS CSCD 北大核心 2016年第3期360-365,共6页
目的:探讨槐定碱对神经胶质瘤U87细胞增殖和侵袭的抑制作用以及U87细胞DNA拓扑异构酶I(DNA TOP I)、EGFR-酪氨酸激酶(EGFR-TK)、基质金属蛋白酶2(MMP2)和氨肽酶N(APN)活性的影响。方法:将不同浓度槐定碱加入到神经胶质瘤U87细胞株中,利... 目的:探讨槐定碱对神经胶质瘤U87细胞增殖和侵袭的抑制作用以及U87细胞DNA拓扑异构酶I(DNA TOP I)、EGFR-酪氨酸激酶(EGFR-TK)、基质金属蛋白酶2(MMP2)和氨肽酶N(APN)活性的影响。方法:将不同浓度槐定碱加入到神经胶质瘤U87细胞株中,利用MTT法测定槐定碱对U87细胞和人脑正常星型胶质HEB细胞生长的抑制作用,酶标仪法检测槐定碱对细胞凋亡蛋白caspase-3活性,采用Transwell小室法分析U87细胞的侵袭能力;采用非放射性NF-κB EMSA试剂盒测定U87细胞中NF-κB表达。结果:随着槐定碱浓度的增加(5、10、25、50、100μmol/L),神经胶质瘤U87细胞生长抑制率不断的增加,但HEB细胞的生长并未受到明显的抑制[(11.23±1.18)%vs(2.43±0.29)%、(22.48±3.21)%vs(3.65±0.42)%、(43.21±4.09)%vs(4.03±0.55)%、(57.31±5.09)%vs(5.21±0.43)%、(77.98±6.98)%vs(7.22±0.78)%,均P<0.05];与空白组比较,槐定碱存在下的U87细胞侵袭能力明显降低[(87.43±7.33)%、(65.12±6.16)%、(50.63±4.56)%、(35.32±4.04)%、(23.46±2.32)%vs(120.32±9.32),均P<0.05]。槐定碱对DNA TOP I、EGFR-TK、APN和MMP-2的半抑制率IC_(50)分别为(22.43±2.21)、(31.25±3.09)、(6.32±0.32)和(8.23±0.63)μmol/L,但U87细胞中凋亡蛋白caspase-3活性呈增强趋势;槐定碱能够下调NF-κB信号的表达。结论:低毒性的槐定碱可能通过降低DNA TOP I、EGFR-TK、APN和MMP-2活性,并下调NF-κB信号通路和激活凋亡caspase-3酶联反应的方式,对神经胶质瘤U87细胞的侵袭、增殖和信号通路产生抑制作用。 展开更多
关键词 槐定碱 神经胶质瘤U87细胞 DNA拓扑异构酶I 表皮生长因子受体-酪氨酸激酶 基质金属蛋白酶2 氨肽酶N
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贝伐珠单抗联合埃克替尼克服一例非小细胞肺癌患者奥希替尼耐药(英文) 被引量:1
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作者 张玲 孙雷 +1 位作者 穆晓燕 季有信 《Chinese Medical Sciences Journal》 CAS CSCD 2019年第4期292-296,共5页
A 61-year-old Chinese woman was diagnosed as primary pulmonary adenocarcinoma of left superior lobe with epidermal growth factor receptor(EGFR)19 del mutation positive.Treatment with icotinib was given,but her disease... A 61-year-old Chinese woman was diagnosed as primary pulmonary adenocarcinoma of left superior lobe with epidermal growth factor receptor(EGFR)19 del mutation positive.Treatment with icotinib was given,but her disease progressed after 6 months remission.CT-guide needle biopsy for the new lesion in inferior lobe of left lung demonstrated intrapulmonary metastasis,and EGFR gene panel by Amplification Refractory Mutation System Polymerase Chain Reaction(ARMS-PCR)confirmed EGFR T790M mutation.Treatment with osimertinib was initiated.After 2 months remission,the disease progressed.Re-biopsy was performed for the tumor in the inferior lobe of left lung,and ARMS-PCR demonstrated no other gene mutation except EGFR 19 del.Icotinib was re-challenged,but disease progressed continuously.Bevacizumab was added,and partial response was achieved after 2-cycle of combination therapy.The non-small cell lung cancer(NSCLC)in this case maintained EGFR activating mutation and lost EGFR T790M mutation was a genetic change after osimertinib treatment.This case suggests the re-challenge of the first-generation EGFR-TKIs combined with bevacizumab may overcome the tumor resistance and prolong survival of NSCLC patient. 展开更多
关键词 Epidermal growth factor receptor-tyrosine kinase inhibitor resistant mutation nonsmall cell lung cancer BEVACIZUMAB
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非小细胞肺癌对EGFR-TKIs获得性耐药的中西医策略研究进展 被引量:1
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作者 郭会 潘方舒 +1 位作者 吴志强 舒琦瑾 《山西中医学院学报》 2016年第2期76-78,F0003,共4页
对于非小细胞肺癌EGFR基因突变阳性患者,EGFR-TKIs是治疗的基石。然而,在取得疗效卓越的同时,获得性耐药问题也相继出现。针对这些TKIs获得性耐药患者,后续如何治疗尚未有标准治疗方案,如何有效克服获得性耐药成为大家关注的焦点。目前... 对于非小细胞肺癌EGFR基因突变阳性患者,EGFR-TKIs是治疗的基石。然而,在取得疗效卓越的同时,获得性耐药问题也相继出现。针对这些TKIs获得性耐药患者,后续如何治疗尚未有标准治疗方案,如何有效克服获得性耐药成为大家关注的焦点。目前,针对TKIs获得性耐药的中药研究越来越多,部分取得较好疗效。通过研究非小细胞肺癌EGFR基因突变阳性患者产生EGFR-TKIs获得性耐药的机制以及耐药后采取的中西医治疗策略,希望能为临床治疗提供一定参考。 展开更多
关键词 非小细胞肺癌 表皮生长因子受体酪氨酸激酶抑制剂 获得性耐药 中西医结合
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吉非替尼可能通过EGFR启动子甲基化诱导肺腺癌细胞继发性耐药 被引量:8
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作者 王起龙 李敏 胡成平 《中国肺癌杂志》 CAS CSCD 北大核心 2015年第4期193-198,共6页
背景与目的在肺腺癌靶向治疗中的吉非替尼继发性耐药是临床遇到的重要问题。本研究旨在探讨吉非替尼是否可诱导肺腺癌PC9细胞发生继发性耐药,以及表皮生长因子受体(epidermal growth factor receptor,EGFR)启动子甲基化在耐药过程中的作... 背景与目的在肺腺癌靶向治疗中的吉非替尼继发性耐药是临床遇到的重要问题。本研究旨在探讨吉非替尼是否可诱导肺腺癌PC9细胞发生继发性耐药,以及表皮生长因子受体(epidermal growth factor receptor,EGFR)启动子甲基化在耐药过程中的作用,拟为肺腺癌耐药提供新的治疗靶点。方法体外培养肺腺癌吉非替尼敏感细胞株PC9,应用不同浓度吉非替尼进行干预。MTT法检测PC9细胞株对吉非替尼的敏感性。亚硫酸氢盐处理后测序法(bisulfite sequencing polymerase chain reaction,BSP)检测肺腺癌PC9细胞株EGFR启动子甲基化水平。使用5-氮杂-2’-脱氧胞苷(5-Aza-dc)对吉非替尼耐药细胞株PC9/GR细胞株进行干预。MTT法检测耐药株PC9/GR对吉非替尼敏感性的变化。结果经过从0.01μmol/L逐渐提升吉非替尼诱导浓度至3μmol/L之后,MTT显示耐药细胞株PC9/GR细胞株半抑制浓度(half maximal inhibitory concentration,IC50)[(3.95±0.23)μmol/L]较之前敏感株PC9[(0.01±0.002)μmol/L]明显升高(P<0.05),BSP显示发生异常甲基化的位点结果比较:PC9/GR甲基化水平明显升高(74%vs59%,P<0.05)。RT-PCR显示PC9/GR细胞株较PC9细胞株EGFR m RNA表达量升高(P<0.05)。使用5-Aza-dc处理PC9/GR细胞后,PC9/GR细胞株IC50较对照组降低[(2.55±0.14)μmol/L vs(3.87±0.034)μmol/L,P<0.05)]。结论吉非替尼体外浓度递增诱导法可诱导PC9细胞株产生吉非替尼继发性耐药,成功构建PC9/GR耐药细胞株。PC9细胞EGFR启动子甲基化异常可能参与了吉非替尼继发性耐药机制。 展开更多
关键词 肺肿瘤 酪氨酸激酶抑制剂 继发性耐药 表皮生长因子受体 甲基化
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FDG-PET/CT response evaluation during EGFR-TKI treatment in patients with NSCLC 被引量:8
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作者 Matthijs H van Gool Tjeerd S Aukema +3 位作者 Koen J Hartemink Renato A Valdés Olmos Houke M Klomp Harm van Tinteren 《World Journal of Radiology》 CAS 2014年第7期392-398,共7页
Over recent years,[18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography(FDG-PET/CT)has proven its role as a staging modality in patients with non-small cell lung can... Over recent years,[18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography(FDG-PET/CT)has proven its role as a staging modality in patients with non-small cell lung cancer(NSCLC).The purpose of this review was to present the evidence to use FDG-PET/CT for response evaluation in patients with NSCLC,treated with epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKI).All published articles from 1November 2003 to 1 November 2013 reporting on 18FFDG-PET response evaluation during EGFR-TKI treatment in patients with NSCLC were collected.In total 7studies,including data of 210 patients were eligible for analyses.Our report shows that FDG-PET/CT responseduring EGFR-TKI therapy has potential in targeted treatment for NSCLC.FDG-PET/CT response is associated with clinical and radiologic response and with survival.Furthermore FDG-PET/CT response monitoring can be performed as early as 1-2 wk after initiation of EGFR-TKI treatment.Patients with substantial decrease of metabolic activity during EGFR-TKI treatment will probably benefit from continued treatment.If metabolic response does not occur within the first weeks of EGFR-TKI treatment,patients may be spared(further)unnecessary toxicity of ineffective treatment.Refining FDG-PET response criteria may help the clinician to decide on continuation or discontinuation of targeted treatment. 展开更多
关键词 NON-SMALL cell lung cancer EPIDERMAL growth factor receptor-tyrosine kinase inhibitors therapy Positron emission tomography-computed TOMOGRAPHY COMPUTED TOMOGRAPHY Response monitoring
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Successful treatment after toxic epidermal necrolysis induced by AZD-9291 in a patient with non-small cell lung cancer:A case report 被引量:2
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作者 Wen Li Xiang He +2 位作者 Hui Liu Jiong Zhu Hui-Min Zhang 《World Journal of Clinical Cases》 SCIE 2021年第29期8846-8851,共6页
BACKGROUND Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute lifethreatening skin reactions.AZD9291 has been developed as a third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase inhib... BACKGROUND Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute lifethreatening skin reactions.AZD9291 has been developed as a third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI)with activity against T790M mutation.CASE SUMMARY Herein we report a 68-year-old woman who developed a large area of skin necrosis and was diagnosed with toxic epidermal necrolysis after AZD-9291 ingestion.To the best of our knowledge,this is the first case reported in patients with EGFR T790M mutation in non-small cell lung cancer(NSCLC).Cabozantinib combined with erlotinib had clinically meaningful effectiveness,with additional toxicity that was generally manageable.CONCLUSION Treatment with AZD-9261 is effective in regressing the growth of the NSCLC and can bring some hope to despairing patients.We hope that more research will be carried out on the association between severe rashes and EGFR-TKIs,and more safe and effective drugs can be developed. 展开更多
关键词 Toxic epidermal necrolysis AZD-9291 Osimertinib Epidermal growth factor receptor-tyrosine kinase inhibitors Non-small cell lung cancer Case report
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Sequential occurrence of T790M mutation and small cell lung cancer transformation in EGFR-positive lung adenocarcinoma:A case report
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作者 Er Hong Xi-Er Chen +4 位作者 Jia Mao Jing-Jing Zhou Ling Chen Jia-Yi Xu Wei Tao 《World Journal of Clinical Cases》 SCIE 2022年第9期2836-2843,共8页
BACKGROUND The emergence of secondary drug resistance when treating epidermal growth factor receptor(EGFR)mutated non-small cell lung cancer(NSCLC)using EGFRtyrosine kinase inhibitors(EGFR-TKIs),seriously affects the ... BACKGROUND The emergence of secondary drug resistance when treating epidermal growth factor receptor(EGFR)mutated non-small cell lung cancer(NSCLC)using EGFRtyrosine kinase inhibitors(EGFR-TKIs),seriously affects the therapeutic efficacy and survival of patients.Here,we report a case of advanced NSCLC focusing on the application of multiple biopsy modalities to reveal the development of multiple resistance mechanisms during targeted therapies.CASE SUMMARY A 54-year-old male patient presented with EGFR 19Del-mutated advanced lung adenocarcinoma,and exhibited the development of a T790M mutation during initial TKI treatment.Following 3 mo of Osimertinib treatment,a mixed response was observed.Tissue biopsy of the progressive lesion showed transformation to small cell lung cancer(SCLC)harboring RB1 and TP53 mutations,with loss of the original T790M mutation.A standard chemotherapy regimen with Anlotinib for SCLC was administered.Repeat biopsy revealed adenocarcinoma combined with SCLC after tumor progression.The patient’s overall survival was 24 mo.CONCLUSION Multiple biopsy modalities can reveal the development of multiple resistance mechanisms which help with treatment decision-making.Comprehensive treatment regimens according to the drug resistance mechanism significantly improved the prognosis of such patients. 展开更多
关键词 ADENOCARCINOMA Epidermal growth factor receptor-tyrosine kinase inhibitor Epidermal growth factor receptor-T790M mutation Small cell lung cancer transformation CHEMOTHERAPY Case report
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Long-term survival of more than 3 years among patients with advanced non-small cell lung cancer treated with chemotherapy
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作者 Rieko Kaira Kyoichi Kaira +9 位作者 Takehito Shukuya Hirotsugu Kenmotsu Akira Ono Haruyasu Murakami Asuka Tsuya Yukiko Nakamura Tateaki Naito Masahiro Endo Nobuyuki Yamamoto Toshiaki Takahashi 《World Journal of Respirology》 2013年第3期110-115,共6页
AIM: To evaluate the prognostic factors of long-term survival of more than 3 years in patients with advanced non-small cell lung cancer(NSCLC). METHODS: We retrospectively analyzed the records of 474 patients with adv... AIM: To evaluate the prognostic factors of long-term survival of more than 3 years in patients with advanced non-small cell lung cancer(NSCLC). METHODS: We retrospectively analyzed the records of 474 patients with advanced ⅢB/Ⅳ NSCLC who received chemotherapy as initial treatment between September 2002 and March 2007.RESULTS: The median survival time(MST) was 12.5 mo and the 3 year and 5 year survival rates were 14.6% and 5.3%, respectively. Long-term survival of more than 3 and 5 years was observed in 65 and 16 patients, respectively. The MST for the 65 patients was61.5 mo(range, 60.1-81.0 mo). In the 474 patients, a good performance status(PS), female sex, non-smoking status and adenocarcinoma histology were significantly associated with a favorable outcome. Furthermore, female sex, a good PS, non-smoking status and adenocarcinoma histology were significantly correlated with longterm survival of more than 3 years and most of these patients(89.2%, 58/65) received epidermal growth factor receptor-tyrosine kinase inhibitors as any line treatment. Survival analysis of long-term survivors showed that a PS of 0 was an independent prognostic factor for predicting favorable outcomes. CONCLUSION: Our results suggest that a good PS and adenocarcinoma histology play an important role in long-term survival of more than 3 years. A PS of 0 was an independent prognostic factor for predicting favorable outcomes in patients with advanced NSCLC who survived for more than 3 years. 展开更多
关键词 NON-SMALL cell lung cancer Long-term SURVIVOR CHEMOTHERAPY Performance status EPIDERMAL growth factor receptor-tyrosine kinase inhibitors
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Efficacy and Safety of Primary Radiotherapy in Combination with EGFR-TKIs for Non-Small Cell Lung Cancer Harboring EGFR Mutation
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作者 Dongxu Ao Meng Wang +5 位作者 Jinyuan Xie Yang Zhang Xinran Zhang Ya Shu Chenshi Lin Qingqing Ye 《Journal of Biosciences and Medicines》 2024年第9期142-154,共13页
Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. ... Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC. 展开更多
关键词 Non-Small Cell Lung Cancer Epidermal growth factor receptor-tyrosine kinase Inhibitor Radiotherapy
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Taking early preventive interventions to manage the challenging issue of acquired resistance to third-generation EGFR inhibitors 被引量:1
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作者 Shi-Yong Sun 《Chinese Medical Journal Pulmonary and Critical Care Medicine》 2023年第1期3-10,共8页
Although the clinical efficacies of third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase in-hibitors(TKIs)such as osimertinib in the treatment of non-small cell lung cancer(NSCLC)with EGFR-activatin... Although the clinical efficacies of third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase in-hibitors(TKIs)such as osimertinib in the treatment of non-small cell lung cancer(NSCLC)with EGFR-activating mutations are promising,drug-acquired resistance inevitably occurs whether they are used as first-line or second-line treatment.Therefore,managing the acquired resistance to third-generation EGFR-TKIs is crucial in the clinic for improving patient survival.Great efforts have been made to develop potentially effective strategies or regimens for the treatment of EGFR-mutant NSCLC patients after relapse following these TKIs therapies with the hope that patients will continue to benefit from treatment through overcoming acquired resistance.Although this approach,which aims to overcome drug-acquired resistance,is necessary and important,it is a passive practice.Taking pre-ventive action early before disease progression to manage the unavoidable development of acquired resistance offers an equally important and efficient approach.We strongly believe that early preventive interventions using effective and tolerable combination regimens that interfere with the process of developing acquired resistance may substantially improve the outcomes of EGFR-mutant NSCLC treatment with third-generation EGFR-TKIs.Thus,this review focuses on discussing the scientific rationale and mechanism-driven strategies for delaying and even preventing the emergence of acquired resistance to third-generation EGFR-TKIs,particularly osimertinib. 展开更多
关键词 Lung cancer Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs) Osimertinib Acquired resistance EGFR mutations
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Low BMI patients with advanced EGFR mutation-positive NSCLC can get a better outcome from metformin plus EGFR-TKI as first-line therapy:A secondary analysis of a phase 2 randomized clinical trial
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作者 Rui Han Jianghua Li +3 位作者 Yubo Wang Tingting He Jie Zheng Yong He 《Chinese Medical Journal Pulmonary and Critical Care Medicine》 2023年第2期119-124,共6页
Background:The synergistic association between metformin and epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)has been confirmed in in vitro studies.It is still controversial which patients can b... Background:The synergistic association between metformin and epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)has been confirmed in in vitro studies.It is still controversial which patients can benefit from metformin plus EGFR-TKIs treatment.Body mass index(BMI)was proved to be independently associated with prolonged progression-free survival(PFS)and overall survival(OS).This study aimed to in-vestigate whether BMI is associated with the synergistic effect of metformin and EGFR-TKIs in advanced EGFR mutation(EGFR m)-positive non-small cell lung cancer(NSCLC)among nondiabetic Asian population.Methods:We performed a post hoc analysis of a prospective,double-blind phase II randomized clinical trial(COAST,NCT01864681),which enrolled 224 patients without diabetes with treatment-naïve stage IIIB-IV EGFR m NSCLC.We stratified patients into those with a high BMI(≥24 kg/m^(2))and those with a low BMI(<24 kg/m^(2))to allow an analysis of the difference in PFS and OS between the two groups.The PFS and OS were analyzed using Kaplan-Meier curves,and the differences between groups were compared using log-rank test.Results:In the univariate analysis,patients who had a high BMI(n=56)in the gefitinib+metformin group(n=28)did not have a better PFS(8.84 months vs.11.67 months;P=0.351)or OS(15.58 months vs.24.36 months;P=0.095)than those in the gefitinib+placebo group(n=28).Similar results were also observed in the low-BMI groups.Strikingly,in the metformin plus gefitinib group,patients who had low BMI(n=69)showed significantly better OS than those with high BMI(24.89 months[95%CI,20.68 months-not reached]vs.15.58 months[95%CI,13.78-31.53 months];P=0.007),but this difference was not observed in PFS(10.78 months vs.8.84 months;P=0.285).Conclusions:Our study showed that nondiabetic Asian advanced NSCLC patients with EGFR mutations who have low BMI seem to get better OS from metformin plus EGFR-TKI treatment. 展开更多
关键词 Non-small cell lung cancer METFORMIN Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs) Body mass index GEFITINIB
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