Metastatic breast cancer

ASCO 2017-What’s new?

AnneMoore,MDandLindaVahdat,MDWeillCornellBreastCenter

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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