乳腺癌的新辅助治疗PPT课件.ppt

1 OPENISSUESINMULTIDISCIPLINARYBREASTCANCERMANAGEMENTMediterraneanSchoolofOncologyRome March30 2012 NEOADJUVANTTHERAPY LuciaMentucciaOncologiaMedica Sora 2 ToimprovesurgicaloutcomesandoptionsForoperablebreastcancer theaimistoincreasethechanceofbreastconservingsurgeryinpatientswhowouldotherwiserequiremastectomyForinoperablelocallyadvancedbreastcancers theaimistoachieveoperabilityTogaininformationontumorresponseTodefineshort termsurrogatemarkersofresponse GoalsofNeoadjuvantTheapyinBreastCancer 3 1523ptswithclinicalT1 3 N0 N1breastcancer Stratification Age ClinicalTumorSize ClinicalNodalStatus Operation Operation NSABPB 18 WolmarkNtal JNatlCancerInstMonogr 2001 ACx4 ACx4 4 36 20 43 cCR 249pts cPR 296pts cSD cPD 140pts 23 4 9 pInv 160pts pNon Inv 26pts pCR 63pts NSABPB 18 ClinicalandPathologicBreastTumorResponse WolmarkNtal JNatlCancerInstMonogr 2001 5 NSABPB 18 SurgeryPerformed 100 80 60 40 20 0 P 0 01 MastLump 60 40 68 32 Preop Chemo Postop Chemo WolmarkNtal JNatlCancerInstMonogr 2001 6 WolmarkNtal JNatlCancerInstMonogr 2001 7 8 9 10 NSABPB 27 PtswithT1c 3N0orT1 3N1breastcancer Randomization ACx4TamX5Yrs ACx4TamX5Yrs ACx4TamX5Yrs Surgery Taxoterex4 Surgery Surgery Taxoterex4 2411pts BearHD etal JClinOncol 2006 24 13 2019 2027 11 NSABPB 27PathologicCompleteResponseinBreast BearHD etal JClinOncol 2006 24 13 2019 2027 12 Diseasefree survival OverallSurvival pCRtoNeoadjuvantChemotherapyiscorrelatedwithimprovedDFS OS NSABPB 27 BearHD etal JClinOncol 2006 24 13 2019 2027 13 NSABPB 27 OverallSurvivalNodalStatus PtswithoutpCR PtswithpCR 14 NSABPB 27 OS DFS RFS 15 Preoperativevspostoperative OverallSurvival TheCochraneLibrary Issue3 2008 16 pCRvsresidualdisease OverallSurvival TheCochraneLibrary Issue3 2008 17 18 Intrinsicsub typeshavedifferentprognosisanddifferentresponsetoprimaryCT 19 0 10 20 30 40 50 60 70 80 90 100 Christofanillietal2006 n 30 Binesetal2003 n 32 Bursteinetal2003 n 40 Kellyetal2006 n 37 Harrisetal2003 n 40 Hurleyetal2002 n 48 Griggsetal2005 n 18 Limentanietal2007 n 31 Giannietal2007 n 115 Lybaertetal2006 n 89 Coudertetal2005 n 33 Buzdaretal2007 n 64 Pernasetal2006 n 16 ResponseRateswithNeoadjuvantTrastuzumab pCR T L IBConly D H T H includingIBC AC T H includingIBC V H includingIBC D cisplatin H includingIBC D H D V T includingIBC X D H AT T CMF H D H T FEC H T FEC H Study L lapatinib V vinorelbine X capecitabine FEC 5 fluorouracil epirubicin cyclophosphamide AT T CMF H IBConly Baselgaetal2007 n 31 Trastuzumab NOAH IBConly Lapatinib NOAH allpatients 20 Paclitaxelq3wkx4 Hx12N 23 FECx4 Hx12 R Paclitaxelq3wkx4N 19 FECx4 BCptsM0 T1 3 No 1 HER2 FISHorICH3 N 42 FEC 5 fluorouracil epirubicin cyclophosphamideH trastuzumab TheMDAndersonStudy BuzdarAU ClinCancerRes2007 Additional22pts 21 66 26 T FEC T FEC Tras 0 20 50 75 ofpatients pCRwithCT Trastuzumab BuzdarAU ClinCancerRes2007 22 MDAndersonNeoadjuvantTrialDFSat72monthsFU BuzdarAetalASCOBreast2009 BuzdarAU ClinCancerRes2007 23 CMFq4wx3cycles NOAH HER2 positiveLABC IHC3 orFISH ATq3wx3cycles Tq3wx4cycles H ATq3wx3cycles H Tq3wx4cycles Hq3wx4cycles CMFq4wx3cycles Hcontinuedq3wtoweek52 n 115 n 113 Surgeryfollowedbyradiotherapya Surgeryfollowedbyradiotherapya 19crossedovertoH GianniLetal Lancet2010 375 377 84 24 Patients 39 20 0 10 20 30 40 50 WithH WithoutH HER2positive p 0 002 pCRratesintheNOAHtrial intent to treatpopulation GianniLetal Lancet2010 375 377 84 25 EFS HER2 positivepopulation L Giannietal TheLancet 2010 26 FutureClinicalPractice 27 Anti HER2Treatment mechanismsofaction 28 ThreeNeoadjuvantTrialsUsingTargetedTherapiesforHER 2PositiveBC 29 LAPATINIBVSTRASTUZUMABINCOMBINATIONWITHNEOADJUVANTANTHRACYCLINE TAXANE BASEDCHEMOTHERAPY PRIMARYEFFICACYENDPOINTANALYSISOFTHEGEPARQUINTOSTUDY GBG44 UntchM LoiblS BischoffJ EidtmannH KaufmannM BlohmerJU HilfrichJ StrumbergD FaschingP KreienbergR TeschH HanuschC GerberB RezaiM JackischC HuoberJ K hnT NekljudovaV vonMinckwitzGfortheGBG AGOstudygroup Thispresentationistheintellectualpropertyoftheauthor presenterContactthemforpermissiontoreprintand ordistribute SanAntonioBreastCancerSymposium CancerTherapyandResearchCenteratUTHealthScienceCenter December8 12 2010 30 31 32 33 ConclusionsfromRun inPhase N 60 NeutropeniaGradeIII IVin82 G CSFmademandatorytogetherwithLTreatmentdiscontinuationsin34 5 Ldosereducedfrom1250to1000mg dDiarrheaGradeIII IVin6 9 Loperamidegivenasstand bymedicationforL vonMinckwitz M Untchetal AnnOncol2010 34 BreastConservationRate 35 Conclusions Anthracycline taxanebasedCT TachievedapCR ypT0 isypN rateof50 inHER2 positivepatients confirmingourpreviousfindings TECHNO GeparQuattro CT L 1250 1000mg resultedinasignificantlylowerpCRrateof35 Caveat 10 morediscontinuationswithL ComplianceofLwithECandDocetaxelwaslowerthanwithT ResultsshouldbeseeninthecontextofotherstudieslikeNeo ALTTO whichusesahigherdoseofL 1500mg d butashorterpre operativetreatmentduration 36 FirstresultsoftheNeo ALTTOtrial BIG01 06 EGF106903 AphaseIII randomized openlabel neoadjuvantstudyoflapatinib trastuzumab andtheircombinationpluspaclitaxelinwomenwithHER2 positiveprimarybreastcancer Jos Baselga IanBradbury HolgerEidtmann SerenaDiCosimo ClaudiaAura EvandrodeAzambuja HenryGomez PhuongDinh KarineFauria VeerleVanDooren PaoloPaoletti AronGoldhirsch Tsai WangChang IstvanLang MichaelUntch RichardD GelberandMartinePiccart GebhartonbehalfoftheNeo ALTTOStudyTeamDecember10 2010 37 StudyDesign 38 Efficacy pCRandtpCR 39 Efficacy Overall Clinical Responseat6weeks w ochemo andatsurgery L lapatinib T trastuzumab L T lapatinibplustrastuzumab 40 Safety NomajorcardiacdysfunctionOnedeathinL Timmediatelyafterendoftreatment Number ofpatientswithAEsatGrade 3 L lapatinib T trastuzumab L T lapatinibplustrastuzumab Includes2patientswithHy sLawcriteriainT andonepatientinL 41 CHERLOBTrial studyplan GuarneriV ASCO2011 121paz 42 pCR breast axilla Nodenegativity Breastconservation CHER LOB EFFICACYOUTCOMES GuarneriV ASCO2011 43 NeoSphere studydesign THP n 107 docetaxel trastuzumab pertuzumab HP n 107 trastuzumab pertuzumab TP n 96 docetaxel pertuzumab SURGERY Studydosing q3wx4 TH n 107 docetaxel trastuzumab Patientswithoperableorlocallyadvanced inflammatory HER2 positiveBCChemo na ve primarytumors 2cm N 417 BC breastcancer FEC 5 fluorouracil epirubicinandcyclophosphamide Locallyadvanced T2 3 N2 3 M0orT4a c anyN M0 operable T2 3 N0 1 M0 inflammatory T4d anyN M0H trastuzumab P pertuzumab T docetaxel GianniLetal SABCS2010 44 H trastuzumab P pertuzumab T docetaxel NeoSpherepCRrates ITTpopulationsummary 50 40 30 20 10 0 TH THP HP TP pCR 95 CI 29 0 45 8 16 8 24 0 6 GianniLetal SABCS2010 45 0 10 20 30 40 50 60 70 TH THP HP TP 20 0 26 0 17 4 36 8 29 1 30 0 63 2 5 9 pCR 95 CI H trastuzumab P pertuzumab T docetaxel GianniLetal SABCS2010 NEOSPHERE pCRandhormonereceptorsstatus 46 L lapatinib T trastuzumab L T lapatinibplustrastuzumabpCRpathologiccompleteresponseHR hormonereceptors pCRbyhormonereceptorstatus BaselgaJetal SABCS2010 47 T trastuzumab L lapatinib T L trastuzumabpluslapatinib CHER LOB pCRratebyHR 48 HORMONERECEPTORSTATUSANDpCR 49 NeoadjuvanttherapyinHER2 operablebreastcancer KeyFindings PatientselectionismandatoryfortheintegrationofnovelagentsincancertreatmentChemotherapy trastuzumabisthegoldstandardDouble HER2blockadeincreasesthepCRrateEndocrinepathwayisstillimportanteveninpresenceofHER2co expressionThepreoperativesettingisidealtotestnewcombinationsthroughthe windowofopportunitymodel 50 ShouldneoadjuvantregimensforHER2 positivediseasealwayscontainanti HER2drug YesNoA IsdualHER2 targetingareasonableoptionforthepreoperativesettingforHER2disease YesNoA 8 5 87 2 4 3 67 4 21 7 10 9 NeoAdjuvantSystemicTherapy StGallen2011 51 VonMinckwitzG SABCS2010 52 VonMinckwitzG SABCS2010 53 VonMinckwitzG SABCS2010 54 OBJECTIVES VonMinckwitzG SABCS2010 55 VonMinckwitzG SABCS2010 56 CHARACTERISTICSOFPATIENTS 57 VonMinckwitzG SABCS2010 58 NeoadjuvantBevacizumabandAnthracycline TaxaneBasedChemotherapyin684TripleNegativePrimaryBreastCancers SecondaryEndpointAnalysisoftheGEPARQUINTOStudy GBG44 GerberBetal ProcASCO2011 Abstract1006 GerberBetal ProcASCO2011 Abstract1006 GerberBetal ProcASCO2011 Abstract1006 59 GEPARQUINTO BenefitofBevacizumabAddedtoNeoadjuvantChemotherapyinTNBCSubgroup GerberBetal ProcASCO2011 Abstract1006 BenefitofbevlimitedtoTNBCsubgrouppCRbreast withbevvswithoutbev TNBCpatients 36 4vs27 8 p 0 021 Allpatients 15 0vs17 5 p NS pCRbreas