复发转移乳腺癌治疗若干问题讨论.ppt

复发转移乳腺癌治疗若干问题讨论NCCNBCUpdate2009307医院乳腺肿瘤科江泽飞,乳癌治疗数千年来主要靠手术切除,Byearly1500ssurgerywasthemaintreatmentmethodforbreastcancerNaturalremediesincluded:milkgoatdungfrogsleadplates,Performingamastectomywithoutanaesthetic,RayterEU)RandomizedphaseIItrial:docetaxel+H:SuperiorRR,TTP,andmedianOScomparedtodocetaxel(Marty,M,etal,JCO2019),Herceptin(H)+Cytotoxics,PhaseIIsofHerceptinwithotherchemo:Vinorelbine:68%RR(BursteinH,JCO2019)Gemcitabine:64%RR(BrufskyA,SABC2019)Capecitabine:77%RR(Xu,SABC2019)Docetaxelqweek:70%RR(BinesJ,SABC2019),aMedianTTPinmonths,GBG-26:continuingHerceptinandswitchingchemotherapyprolongsTTP,vonMinckwitzetal2019,Time(weeks),Xeloda,Herceptin+Xeloda,Probability,0.0,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1.0,HR=0.69(2-sidedp=0.034;1-sidedp=0.017),24.3(5.6)a,35.6(8.2)a,10,0,20,40,50,60,70,80,100,30,90,2.6months,TimetoProgessionasAssessedbyIRC,0.2,0.4,0.6,0.8,0.0,1.0,0,CumulativeProgression-Free,10,20,30,40,50,60,Time(weeks),70,aMedianTTPinmonths,HerceptinplusXelodadoublestheTTPincrementvslapatinibplusXeloda,EMEALapatinibSummaryofProductCharacteristics;USLapatinibPrescribingInformation2019;Ryanetal2019;vonMinckwitzetal2019,Probability,0,10,20,30,40,Timefromrandomisation(weeks),0.0,0.2,0.4,0.6,0.8,1.0,50,60,Herceptin+lapatinibLapatinibHR=0.73;p=0.008,OShaughnessyetal2019,EGF104900:Herceptinpluslapatinibissuperiortolapatinibalone(PFS),12.0(2.8)a,8.1(1.9)a,aMedianPFSinmonths,0.9months,现代分子肿瘤学发展到分类治疗时代化疗应有的作用和地位?,不同类型乳癌不同的治疗模式,Negative,阳性,ER/PgR,HER-2,Negative,Positive,化疗,HormoneNon-responsive,内分泌治疗,分子靶向治疗,选择最佳的一线化疗方案,蒽环类+紫杉类目前最有效的治疗乳癌化疗方案之一,AT方案ADM50mg/m2IVd1orEPI75100mg/m2Taxol175mg/m2IVby3-horTaxotere75mg/m21/21-28d,蒽环类和紫杉类目前最有效的治疗乳癌化疗方案之一,对于未用过蒽环类和紫杉类的晚期患者可能是术前新辅助治疗的最佳方案没有在术后辅助治疗的推荐方案中复发转移患者中应用机会不多不是蒽环类治疗失败患者的最佳选择,蒽环类成为辅助治疗基本药物复发转移乳癌的一线治疗?,复发转移乳腺癌化疗蒽环类治疗失败HR-ABC,GT(吉西他滨+紫杉醇),健择联合紫杉醇一线治疗复发转移乳腺癌总生存率结果,总体生存几率,复发转移乳腺癌化疗蒽环类治疗失败HR-ABC,XT(多西他赛+卡倍他滨),当越来越多的患者接受紫杉类作为术后辅助治疗的时候复发转移病人的一线首选化疗？,复发转移乳腺癌化疗药物选择原则cNCCN2019,1、紫杉类治疗失败的患者，无标准方案推荐。2、可以考虑的药物有卡培他滨、长春瑞滨、吉西他滨和铂类，3、可以采取单药或联合化疗GP/NP/XNGXGN,PhaseIIITrialofGemcitabinePlusDocetaxel(GD)ComparedtoCapecitabinePlusDocetaxel(CD)withPlannedCrossovertotheAlternateSingleAgentinMetastaticBreastCancer(MBC),SeidmanA,etalASCO2009,Abstract1000OralAbstractSession,67,GDvsCD:StudyDesign,68,Seidmanetal.ASCO2009.Abstract1000,DosesG:1000mg/m2d1,8C:1000mg/m2BIDd1-14D:75mg/m2d1q3w,Gemcitabine-docetaxel,N=472,Capecitabine-docetaxel,Capecitabine,Gemcitabine,untilprogression,untilprogression,OffstudyFollow-up,Primaryendpoint:TTPSecondaryendpoints:toxicities,ORR,OS,OffstudyFollow-up,MBCwithnotaxaneforMBC6monthsprior,Stratificationfactors:1stvs2ndlinetreatmentPrioranthracyclineVisceraldiseaseECOGPSMeasurablevsnon-measurabledisease,GDvsCD:ResponseandSurvival,69,Seidmanetal.ASCO2009.Abstract1000,延长复发转移乳癌生存的策略,选择最佳的一线治疗合理选用综合治疗手段HR(+)可以首选内分泌治疗及时采用分子靶向治疗适合的联合化疗以及单药维持治疗积极局部治疗合理的姑息治疗,建立科学合理的骨转移综合诊疗体系,放射治疗,外科手术,内分泌治疗,化学治疗,分子靶向治疗,双磷酸盐类,脑转移并非完全无药可治,Treatmentofmetastaticcentralnervoussystemdisease,With10%ORR,lapatinibtrialsinmCNSdiseasefailedprimaryendpoints,Oberhoffetal2019;Linetal2019,2019;Riveraetal2019;Tsaoetal2019;Addeoetal2019;Heddeetal2019;Ekeneletal2019,*ExtensionstudyofXelodaaddedtolapatinibafterlapatinibfailuremCNS,metastaticcentralnervoussystem;WBRT,whole-brainradiationtherapy,ORR(%),Loweretal2019(n=80,MBC)Kirschetal2019(n=47,MBC)Churchetal2019(n=22,MBC)Lichinitseretal2019(n=15,EBC)Vermaetal2019(n=52,MBC)Bartschetal2019(n=53,MBC)Pinderetal2019(n=292,MBC)Brufskyetal2019(n=332,MBC)Parketal2009(n=78,MBC)Nametal2019(n=56,MBC)Churchetal2019(n=26,MBC)Dawoodetal2019(n=280,invasivebreastcancer),49.9261260.611.22133.517.513.612.811.911.6,28.9a9319.8NR9b+3c29.45.55.54.03.06.1,MedianOS,months,FromdiagnosisofmCNSdiseaseaPatientswithHER2-negativeandHER2-positivetumours;bPatientsreceivedchemotherapyonly;cPatientsreceivednofurthersystemictherapy,HerceptinprolongssurvivalinpatientswithmCNSdisease,Herceptin,NoHerceptin,Study,PreferredTherapyRegimens:NCCNguidelines,Thebestmanagementofanycancerpatientisinaclinicaltrial,AdaptedfromNCCNPracticeGuidelinesinOncology2019;v.1,肿瘤生物学行为决定乳癌治疗选择,Negative,阳性,ER/PgR,HER-2,Negative,Positive,化疗CapxolIxabepilone,内分泌治疗瑞宁得氟维司群,Herceptin,Lapatinib,Avastin,注射用重组抗HER-2人源化单克隆抗体同步/序贯联合长春