report back from asco on metastatic breast cancer
TRANSCRIPT
Metastatic breast cancer
ASCO 2017-What’s new?
AnneMoore,MDandLindaVahdat,MDWeillCornellBreastCenter
SHAREWebinar
June20,2017
BreastcancerintheUS-2017NewesFmateddata
• 3.5millionwomenarelivingwithahistoryofbreastcancer– EsFmate35,000men
• 155,000womenarelivingwithahistoryofmetastaFcbreastcancer
• 26,500womenareliving10yearsormorewithmetastaFcbreastcancer
MarioPo,CancerEpidemiolBiomarkersPrev2017;26:809
BreastcancerintheUS-2017
“WithopFmalcare,womenwithMBCcanandoYendoliveforyearswithreasonablequalityoflife,albeitundergoingconstanttreatmenttokeeptheirdiseaseundercontrol.”
MarioPo,CancerEpidemiolBiomarkersPrev2017;26:809
Whathavewelearnedinthepastfewyears?
Everybreastcancerisdifferent!
DCKoboldtetal.Nature000,1-10(2012)doi:10.1038/nature11412
Althoughallindividualbreastcancersaredifferent,thereare4groups
• HormonereceptorposiFve– LuminalA– LuminalB
• HormonereceptornegaFve• Her2posiFve
Everybreastcancerisdifferentandtherearefrequentlydifferencesbetweentheprimarycancerandthemetastasis
Biopsyofthemetastasisisveryimportant!
AmirEetal.JCO2012;30:587-592
Everybreastcancerisdifferentandtherearefrequentlydifferencesbetweentheprimarycancerandthemetastasis
Biopsyofthemetastasisisveryimportant!
AmirEetal.JCO2012;30:587-592
37%oftheFme,theER/PRorHER2inthemetastasisisdifferentfromtheoriginalprimarycancer
Shouldallbreastcancers,primaryormetastaFc,betestedfor
“nextgeneraFonsequencing”?
PrecisionMedicineanalysessuchasFoundaFonOnetestforgenemutaFonsinthecancer…Atpresent,thisisnotarouFneanalysisforbreastcancer.TherewasnonewinformaFonatASCOthatleadsmetothinkthisshouldbedonerouFnely..Butkeepasking!
ASCO2017
• HeldinChicago-almost40,000aPendeesfrommorethan150countries.
• PaperswithnewfindingsaboutcancerweresubmiPedandselectedforpresentaFon---almost12,000werepublishedintheProceedings
ASCO2017-almost12,000abstracts
ASCO2017:BreastCancerHighlights
Hormonereceptor(ERand/orPRposiFve)metastaFcbreastcancerWhatareacFvetreatmentsforthisdisease?
• Postmenopausal– Aromataseinhibitor
• AnastrazoleorLetrozole(non-steroidal)• Exemestane(steroidal)
– AromataseinhibitorwithCellCyclininhibitor• Palbociclib(Ibrance)• Ribociclib• Abemaciclib
LetrozoleandPalbociclib(Ibrance)
2015-PALOMA1trialshowedthatwomenwithER+metastaFcbreastcancerwhotookletrozole+palbociclibastheirfirsttreatmentaYerthediagnosisofmetastaFcdiseasehadtwiceaslongaresponsetothetreatmentthaniftheytooktheletrozolealone.2017-Doesthatmeantheywilllivelongeriftheystartthe2medicaFonsimmediatelyattheFmeofdiagnosisofmetastaFcbreastcancer?
ASCO2017
PALOMA1-FOLLOWUP2017Overallsurvivalwasnotaffectedifawomantook
letrozolealoneorletrozole+palbociclibattheFmeofdiagnosisofmetastaFcbreastcancer.
• ThisisprobablybecausewehavesomanyothermedicinestouseifawomanhasprogressionofthediseaseaYerfirst-linetherapy(whethertheletrozolealoneorletrozole+palbociclib).
• BUTshemayhavealongerFmebeforeshehastochangemedicinesifshehasletrozole+palboascomparetoletrozolealone
WhatdoesthismeanforyouifyouhaveafirstmetastasisofER+breastcancer?
• Aromataseinhibitoralone(letrozole)maybethebesttreatmentforyouifthediseaseis“indolent”andnotfastgrowing
• Letrozole+palbociclibmightbebePerforyouifthediseaseismoreacFveandweneedafasterresponsetotreatment
ASCO2017MONARCH2TRIAL
• ERposiFvemetastaFcbreastcancer• Adifferentcellcyclininhibitor,abemaciclib,andadifferenthormonetreatment,fulvestrant(Faslodex)inadifferentgroupofwomen.
ASCO2017
ASCO2017ERposiFvemetastaFcbreastcancer
Adifferentcellcyclininhibitorandadifferenthormonetreatmentinadifferentgroupofwomen
• MONARCH2-Goodnews– ThewomenwithfulvestrantANDthenewdrug,abemaciclibhadlessprogressionoftheirdiseaseatafollowupof19monthscomparedtothewomenwithfulvestrantalone
– Willthesewomenlivelongerbyaddingabemaciclibtothefulvestrant?
ER+breastcancer
• Wehaveanewapproach(cellcyclininhibiFon)andmorechoicestotreatthisdisease
• LongerFmebeforeweswitchtochemotherapy
MetastaFcHER2PosiFvebreastcancer
MetastaFcHER2posiFvebreastcancer
• HercepFn(trastuzumab)isatargeteddrugfortheHER2receptor.
• Whencombinedwithchemotherapy,itisveryacFveagainstmetastaFcdisease;notveryacFvewhengivenalone
• Howabout“dual”blockadeoftheHER2receptor-using2drugsagainstHER2insteadofonedrug?
MetastaFcHER2posiFvebreastcancer:Dualblockade
• Pertuzumab+HercepFn+taxotere(Cleopatratrial)ismoreacFvethanHercepFnandtaxoterealoneformetastaFcdisease-anewstandardofcareformetastaFcbreastcancer
• LapaFnib(apill)+HercepFn+chemotherapy• NeraFnib(apill)+HercepFn+chemotherapy
MetastaFcHER2posiFvebreastcancer:Dualblockade:MARIANNETRIAL
• WomenwithmetastaFcher2+breastcancerreceivedoneofthesetreatmentsasfirstline:– HercepFn+taxotereortaxol– T-DM1(Kadcyla:hercepFnaPachedtoachemodrug,maytansine)
– T-DM1+Pertuzumab(Perjeta)=dualblockade• Allthetreatmentswereequal-dualblockadewasnotsuperior-
• ThisdoesshowthevalueofTDM-1
TriplenegaFvebreastcancer
• AlltriplenegaFvebreastcancersarenotthesamealthoughallareER,PRandHER2negaFve
• Muchresearchonfiguringthisoutsowecanfindtargetstotreat
• Howaboutimmunotherapy?
TriplenegaFvebreastcancer
• Howaboutimmunotherapy?• Pembrolizumab(Keytruda)isacFveinsomecancerssuchasmelanomaorlungcancer
ImmunotherapyhaspromiseinmetastaFcbreastcancer
ImmunotherapyinBreastCancer
• HowdoweselecttherightpaFent?• Howdoweselecttherighttumor?• HowdoweselecttherightpaFentwiththerighttumor?
BRCAmutaFoncarrierswithmetastaFcbreastcancer
• WehaveanacFvenewdrug:Olaparib,aPARPinhibitor
BRCAmutaFoncarrierswithmetastaFcbreastcancer
BRCAmutaFoncarrierswithmetastaFcbreastcancer
HighlightsofASCO2017Openingnewpathways
• ForpaFentswithBRCAmutaFon
– PARPinhibitorinBRCAmutaFoncarriers-aimedatthespecificproblemcausedbythegenemutaFon
• ForpaFentswithER+breastcancer:– CellcyclininhibiFon–aimedatslowingdowncellgrowthandmakingcellsmoresensiFvetoanF-estrogentherapies
HighlightsofASCO2017Openingnewpathways
• ForpaFentswithHER2+breastcancer
– ExpandingonthesuccessofHercepFn–addingmoreanF-HER2drugs
• ForpaFentswithTripleNegaFvebreastcancer– Breakingthecode
• Immunotherapy—justthebeginning?
ClinicaltrialsatWeillCornellMedicine
WeillCornellBreastCenterClinicalTrials–AdjuvantTrials
ER+/PR+ TNBCHER2+ BRCA+
• S1207:PhaseIIIRandomized,Placebo-ControlledClinicalTrialEvaluaFngTheUseofAdjuvantEndocrineTherapy+/-OneYearofEverolimus
• POSITIVE:PregnancyOutcomeandSafetyofInterrupFngTherapyforWomenwithEndocrineResponsiveBreastCancer
• S1418:A
Randomized,PhaseIIITrialtoEvaluatetheEfficacyandSafetyofMK-3475asAdjuvantTherapyforTripleReceptor-NegaFveBreastCancer
• EA1131:PlaFnumBasedChemotherapyorObservaFoninTreaFngPaFentsWithResidualTriple-NegaFveBasal-LikeBreastCancerFollowingNeoadjuvantChemotherapy
• NSABPB55:ArandomizedphaseIIIStudytoaccesstheefficacyandsafetyofolaparibversusplaceboasadjuvanttreatmentinptwithGermlineBRCA1/2mutaFons
Targeted
SupporFveCare/
CorrelaFve/Biobank
• TripleNega<veBreastCancerProgram:ClinicalDatabaseandTissueCollecFonProjectfortheStudyofBreastCancer
• Stress-Reduc<on&Self-Healing:APilotStudyofGuidedMeditaFon
• PrecisionMedicine:ToidenFfythefrequencyandrateofacFonablemutaFonsinadvancedcancers
• Biomarkers:ToidenFfythefrequencyandrateofacFonablemutaFonsinadvancedcancers
• SCPSa<sfac<onSurvey:PaFentandPhysicianSaFsfacFonSurveyofSurvivorshipCarePlans
WeillCornellBreastCenterClinicalTrials–MetastaFcTrials
ER+/PR+ TNBCHER2+ BRCA+
• E2112:ARandomizedPhaseIIITrialofEndocrineTherapyplusEnFnostat/PlaceboinMenandWomenwithHormoneReceptor-PosiFveAdvancedBreastCancer
• IMMU-132-01:A
PhaseIIStudyofIMMU-132(hRS7-SN38AnFbodyDrugConjugate)inPaFentswithEpithelialCancer
• MILLENNIUM:APhase1b/2StudyofMLN0128inCombinaFonWithExemestaneorFulvestrantTherapyinPostmenopausalWomenWithER+/HER2-AdvancedorMetastaFcBreastCancer
• AAAM1906:PhaseIITrialofRuxoliFnibinCombinaFonwithTrastuzumabinMetastaFcHER2PosiFveBreastCancer
• PUMA:APhaseIIITrialofNeraFnib+CapecitabineVersusLapaFnib+CapecitbineInPaFentsWithHER2+MetastaFcBreastCancer
• Macrogenics:APhase3,RandomizedStudyofMargetuximabPlusChemotherapyvsTrastuzumabPlusChemotherapyintheTreatmentofPaFentswithHER2+MetastaFcBreastCancer
• CELLDEX:ARandomizedMulFcenterPivotalStudyofCDX-011(CR011-vcMMAE)inPaFentswithMetastaFc,GPNMBOver-Expressing,Triple-NegaFveBreastCancer
• Rexahn:AMulF-Center,DoseFinding,OpenLabel,Phase1studyofRX_5902inSubjectswithAdvancedorMetastaFcSolidTumors
• Oncotherapy:APhaseIStudyofOTS167PO,aMELKinhibitor,inPaFentswithAdvanced,TripleNegaFveBreastCancer
• PharmaMar:AMulFcenterPhaseIIClinicalTrialofPM01183inBRCA1/2-AssociatedorUnselectedMetastaFcBreastCancer
Targeted
• GenentechPathway:Open-labelPhaseIIaStudyEvaluaFngTrastuzumab/pertuzumab,ErloFnib,Vemurafenib,andVismodegibinPt'sW/AdvancedSolidTumorsWithMutaFonsorGeneExpressionAbnormaliFesPredicFveofResponsetoOneofTheseAgents
• LY2157299:LY2157299
MonohydrateandRadiotherapyinMetastaFcBreastCancer
• TLR7:PhaseI/IIstudyofTLR7agonistImiquimod,Cyclophosphamide,andRadiotherapyinBreastCancerPaFentswithChestWallRecurrenceorSkinMetastases
SupporFveCare/
CorrelaFve/Biobank
• TripleNega<veBreastCancerProgram:ClinicalDatabaseandTissueCollecFonProjectfortheStudyofBreastCancer
• Stress-Reduc<on&Self-Healing:APilotStudyofGuidedMeditaFon
• PrecisionMedicine:ToidenFfythefrequencyandrateofacFonablemutaFonsinadvancedcancers
• Biomarkers:ToidenFfythefrequencyandrateofacFonablemutaFonsinadvancedcancers
• SCPSa<sfac<onSurvey:PaFentandPhysicianSaFsfacFonSurveyofSurvivorshipCarePlans
TheFuture
Thefutureisbright…Ourclinicaltrialsarethriving…Supportresearch!ThankyoutomycolleaguesattheBreastCenter,
DrsAndreopoulou,CiglerandVahdat
AndthankyoutoDrMauraDicklerforsharingherrecentpresentaFononHighlightsfromASCO