非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂英文.pptx
《非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂英文.pptx》由会员分享,可在线阅读,更多相关《非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂英文.pptx(57页珍藏版)》请在咨信网上搜索。
1、2024/4/15YMC1Epidermal growth factor receptor-tyrosine kinase inhibitor in non-small-cell lung cancerYuh-Min Chen,MD,PhD.Chest Dept.,Taipei VGH2024/4/15YMC2Survival(anti-apoptosis)PI3-KActivationoftheepidermalgrowthfactorreceptortyrosineActivationoftheepidermalgrowthfactorreceptortyrosinekinase(EGFR
2、-TK):apivotaldriverofcarcinogenesiskinase(EGFR-TK):apivotaldriverofcarcinogenesisEGFR-TKEGFRLigandRASRAFSOSGRB2PTENAKTSTAT3MEKGene transcriptionCell-cycle progressionDNAMycMycCyclin D1JunFosP PMAPKProliferation/maturationChemotherapy/radiotherapyresistanceAngiogenesisMetastasisBalaban et al 1996;Aki
3、moto et al 1999;Wells 1999;Woodburn 1999;Hanahan 2000;Raymond et al 2000 Cyclin D1pYpYpY2024/4/15YMC3RppRExtracellularIntracellularMembranepKpKpppTGFaSubstrateSubstrateSignallingMoleculesProliferationInhibit ApoptosisAngiogenesisMetastasisNucleusMonoclonalAntibodiesEGFRTyrosineKinaseInhibitors2024/4
4、/15YMC4IDEAL1and2trialdesignGefitinib250 mg/dayGefitinib500 mg/dayContinue gefitinib until diseaseprogression or unacceptable toxicityIDEAL,IressaTM Dose Evaluation in Advanced Lung cancerRandomisationlIDEAL 1(n=209)1 or 2 prior regimenslIDEAL 2(n=216)2 prior regimensPrimary endpointslObjective tumo
5、ur responselSymptom improvement(IDEAL 2)lSafety(IDEAL 1)2024/4/15YMC5Median time to improvement-symptoms and QOL*Time of 1st assessmentMedian time toimprovement,daysSymptom/QOLmeasureLCSFACT-L8*29*2024/4/15YMC6IDEAL1and2:overallsurvivalbysymptomimprovement(250mg/day)Probability 1.00.80.60.40.20.0IDE
6、AL 1Months from randomisationImprovementNo improvement2740183013.33.5Patients(n)Deaths(n)Median(months)0 2 4 6 8 101214 1618204458265613.63.7Patients(n)Deaths(n)Median(months)1.00.80.60.40.20.0ProbabilityIDEAL 2Months from randomisation02 4 6 8 10 1214 16 1820Douillard et al 2002;Lynch et al 2003202
7、4/4/15YMC7ISEL(IRESSA Survival Evaluation in Lung Cancer):Clinical Trial DesignRandomisation Gefitinib(250 mg)+*BSCPlacebo+*BSC SURVIVALSecondary:TTF,ORQoL,safetyPrimaryendpoint:ENDBENEFIT2:1ratioA double blind Phase III survival study comparing IRESSA(250mg)plus BSC vs.placebo plus BSC in patients
8、with advanced NSCLC who have received 12 prior chemotherapy regimens and are refractory or intolerant to their most recent regimen1692 patients in 210 centres across 28 countries 342 patients of oriental origin No Japanese/US sites*BSC=Best Supportive CareLancet 2005;366:1527-37 2024/4/15YMC8ISEL-Ov
9、erallSurvivalPercentsurvivingTime(months)At risk:Gefitinib 1129 1023 901 761 588 455 325 245 175 113 76 45 19 9 IRESSA -PlaceboPlacebo 563 517 446 382 289 220 160 115 77 44 28 20 12 4 2GefitinibplaceboMedian(months)5.65.11yrsurvival27%21%HR=0.89(0.77,1.02),p=0.0871StratifiedlogranktestN=1692,deaths=
10、976Coxanalysis,p=0.02992024/4/15YMC9ISELSurvival:OrientalsPercentsurvivingTime(months)At risk:Gefitinib 235 221 199 179 145 119 95 78 64 51 40 25 12 8 IRESSA -Placebo Placebo 107 97 84 74 56 43 35 29 22 13 8 7 3 1 15.5 M5.5 M9.5 M9.5 M2024/4/15YMC10J Chemother 2005;17:6792024/4/15YMC11RESULTS3CR,9PR
11、,withaR.R.of 33.3%SD14,control rate of 72.2%Alltreatment-relatedtoxicitieswerefewandmildinseverity,exceptonepatientsufferedfromreversiblegrade3interstitialpneumonitisJ Chemother 2005;17:6792024/4/15YMC12%SurvivalMedian survival:9.5 months One-year survival rate:45.1%J Chemother 2005;17:6792024/4/15Y
12、MC13%SurvivalFig.10102030405060708090100036912151821MonthsCompleteorpartialresponse(n=12)median20.1MStableorprogressivedisease(n=24)median4.7MSurvival according to response or not15.4月月J Chemother 2005;17:6792024/4/15YMC14StudyDesignofBR.21 Stratified by:Centre PS (0/1 vs 2/3)Response to prior treat
13、ment (CR/PR:SD:PD)Prior regimens (1 vs 2)Prior platinum (yes vs no)Tarceva150mg dailyPlaceboRANDOM I SEPS=performance status21 N Engl J Med 2005;353:123322024/4/15YMC15BR.21:BR.21:S Significantignificant clinicalpredictorsofresponsetoclinicalpredictorsofresponsetoTarcevaTarcevaTarcevatreated pts(n)R
14、.R.(%)p value*Gender Female(146)14.4 0.006Male(281)6.1HistologyAdenocarcinoma(209)13.90.001Other(218)4.1EthnicityAsian(53)18.90.02Other(374)7.5Ever smoked*Yes(311)3.80.001No(93)24.7Unknown(23)13.0*Significance between subgroups*Data collected retrospectivelyIn multiple logistic-regression analyses,o
15、nly never having smoked(p0.001)and adenocarcinoma histology(p=0.01)were associated with responseShepherd et al.NEJM 2005;353:1232024/4/15YMC16ImprovementinSurvivalwithTarceva42.5%improvement in median survivalSurvival distribution functionSurvival time(months)HR=0.73,p0.001*1.000.750.500.25005101520
16、2530TarcevaPlacebo N Engl J Med 2005;353:12332 Tarceva(n=488)Placebo(n=243)Median survival(months)6.7 4.7 1-year survival(%)31 21 2024/4/15YMC17BR.21:Timetosymptomdeterioration(months)Placebo Tarceva179179153n348353298n1.9(1.82.8)2.9(24.8)3.7(24.9)Median(95%CI)0.022.8(2.43)Pain0.014.7(3.86.2)Dyspnea
17、0.044.9(3.87.4)Cough p value*Median(95%CI)*Log-rank test,unadjusted for multiple symptoms Bezjak A,et al.J Clin Oncol 2006;24:38317Shepherd F,et al.N Engl J Med 2005;353:123322024/4/15YMC18TRUST:TarcevaMO18109AnexpandedaccessclinicalprogramofTarceva(erlotinib)inptswithadvancedstageIIIB/IVNSCLCLungCa
18、ncer2008LungCancer20082024/4/15YMC19PatientPopulation&ResponseFromMay2005toJuly2006,300patientswereenteredfrom14hospitalsinTaiwan.Thisanalysiswasbasedon299patientswhoreceivedatleastonedoseofTarceva.2024/4/15YMC20ResponserateandcontrolratebypretreatmentResponserateandcontrolratebypretreatmentcharacte
19、risticsandskintoxicitycharacteristicsandskintoxicityPatient characteristicsPatient numberResponse rate(%)Response rate(%)p-valueControl rate(%)p-valueGender Male Female140133202037.637.60.00130.001363.682.70.0004Age 65 6516011334.434.420.420.40.01150.011573.172.60.9185Performance status 0/1232263512
20、28.822.941.70.46910.339272.671.483.30.88850.4124Stage IIIB IV5621517.931.20.049269.673.50.5651Histology Adenocarcinoma Squamous cell carcinoma1904834.734.712.512.50.00270.00277960.40.0079Present treatment as Second line Third line16710229.926.50.541370.776.50.2983Smoking status Non-smoker Former or
21、current smoker15811533.533.521.721.70.0330.03379.164.40.0067Skin toxicity-1No rash Rash2924410.310.330.730.70.02160.021641.476.60.0001Skin toxicity-2 No rash or grade 1 Rash grade 2,3,or 411915419.319.335.735.70.0030.00361.381.80.0002The best response rates were a 29%partial response and 29%partial
22、response and 44%stable44%stable disease in 273 patients who had response data available.Non-smoking(Non-smoking(p p=0.033),adenocarcinoma=0.033),adenocarcinoma/BAC BAC(p p=0.0027),female(=0.0027),female(p p=0.0013),=0.0013),aged less than 65 years(p=0.0115),stage IV(p=0.0492),patients with skin rash
23、 skin rash(p p=0.0216),and a higher grade of skin rash(=0.0216),and a higher grade of skin rash(p p=0.003)=0.003)were significantly correlated with response to treatment.2024/4/15YMC210.000.250.500.751.00Progressionfreesurvival(Months)061020CensoredobservationsFig.1Freefromprogression8421214161822Ti
24、me to disease progression of 299 NSCLC pts treated with erlotinib.The median time to disease progression was 5.6 months5.6 months(95%C.I.:4.4 6.5 months,45 pts censored)2024/4/15YMC22EGFR-TKIvs.chemotherapeuticagentsinsalvagechemotherapy2024/4/15YMC23In conclusion,both chemotherapeutic agents,such a
25、s In conclusion,both chemotherapeutic agents,such as docetaxel alone or gemcitabine+vinorelbine,and docetaxel alone or gemcitabine+vinorelbine,and gefitinibgefitinib,are appropriate salvage regimens for Chinese,are appropriate salvage regimens for Chinese NSCLC pts who have failed previous chemother
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- 细胞 肺癌 表皮 生长因子 受体 酪氨酸 激酶 抑制剂 英文
1、咨信平台为文档C2C交易模式,即用户上传的文档直接被用户下载,收益归上传人(含作者)所有;本站仅是提供信息存储空间和展示预览,仅对用户上传内容的表现方式做保护处理,对上载内容不做任何修改或编辑。所展示的作品文档包括内容和图片全部来源于网络用户和作者上传投稿,我们不确定上传用户享有完全著作权,根据《信息网络传播权保护条例》,如果侵犯了您的版权、权益或隐私,请联系我们,核实后会尽快下架及时删除,并可随时和客服了解处理情况,尊重保护知识产权我们共同努力。
2、文档的总页数、文档格式和文档大小以系统显示为准(内容中显示的页数不一定正确),网站客服只以系统显示的页数、文件格式、文档大小作为仲裁依据,平台无法对文档的真实性、完整性、权威性、准确性、专业性及其观点立场做任何保证或承诺,下载前须认真查看,确认无误后再购买,务必慎重购买;若有违法违纪将进行移交司法处理,若涉侵权平台将进行基本处罚并下架。
3、本站所有内容均由用户上传,付费前请自行鉴别,如您付费,意味着您已接受本站规则且自行承担风险,本站不进行额外附加服务,虚拟产品一经售出概不退款(未进行购买下载可退充值款),文档一经付费(服务费)、不意味着购买了该文档的版权,仅供个人/单位学习、研究之用,不得用于商业用途,未经授权,严禁复制、发行、汇编、翻译或者网络传播等,侵权必究。
4、如你看到网页展示的文档有www.zixin.com.cn水印,是因预览和防盗链等技术需要对页面进行转换压缩成图而已,我们并不对上传的文档进行任何编辑或修改,文档下载后都不会有水印标识(原文档上传前个别存留的除外),下载后原文更清晰;试题试卷类文档,如果标题没有明确说明有答案则都视为没有答案,请知晓;PPT和DOC文档可被视为“模板”,允许上传人保留章节、目录结构的情况下删减部份的内容;PDF文档不管是原文档转换或图片扫描而得,本站不作要求视为允许,下载前自行私信或留言给上传者【胜****】。
5、本文档所展示的图片、画像、字体、音乐的版权可能需版权方额外授权,请谨慎使用;网站提供的党政主题相关内容(国旗、国徽、党徽--等)目的在于配合国家政策宣传,仅限个人学习分享使用,禁止用于任何广告和商用目的。
6、文档遇到问题,请及时私信或留言给本站上传会员【胜****】,需本站解决可联系【 微信客服】、【 QQ客服】,若有其他问题请点击或扫码反馈【 服务填表】;文档侵犯商业秘密、侵犯著作权、侵犯人身权等,请点击“【 版权申诉】”(推荐),意见反馈和侵权处理邮箱:1219186828@qq.com;也可以拔打客服电话:4008-655-100;投诉/维权电话:4009-655-100。