Carcinoma della mammella HER2 positivo metastatico · Unit of Inves,gave Clinical Oncology Is,tuto di Candiolo (IRCCS) Carcinoma della mammella HER2 positivo metastatico

UnitofInves,ga,veClinicalOncologyIs,tutodiCandiolo(IRCCS)

Carcinoma della mammella HER2 positivo metastatico

DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo

! Treatmentalgorithmsremaindynamicandthereismoretolearnregardingtheop,miza,onofHER2-directedtherapiesinthemetasta,cseDngaEerpriorexposuretotheseagentsinthe(neo)adjuvantseDng

! Howcanwereliablyiden,fypa,entswhomight—ormightnot—benefitfromapar,cularHER2-targetedtherapy?

MARIANNE accompanying editorial

KomalJhaveri,JClinOncol35;127,2017


Current treatment choices

Chemotherapyalone?(FM)


Efficacy resutls of PERUSE

BachelotP4-21-04


Exposure to neo/adjuvant treatments

BachelotP4-21-04


Docetaxel or Paclitaxel with trastuzumab and pertuzumab?

BachelotP4-21-04


Docetaxel or Paclitaxel with trastuzumab and pertuzumab?

BachelotP4-21-04


First line therapy with Trastuzumab and pertuzumab + AIs in patients with HER2-positive/HR positive tumors

ArpinoS3-04


PERTAIN: Primary End-Point

ArpinoS3-04


P+H+AI(N=54)

H+AI(N=56)

EventsN(%) 29(53.7%) 43(76.8%)

MedianPFS,months 21.72 12.45

(95%C.I.) (12.43-32.45) (6.21-18.53)

∆months 9.27

HR(95%C.I.) 0.55(0.34-0.88)

p-value 0.0111

Efficacy in patients not receiving chemotherapy

CourtesyofGraziaArpino


! Safe(anduseful)toaddmaintenanceendocrinetherapywithanaromataseinhibitoraEerchemotherapy.

! Resultsofthestra,fica,onsubgroupsanalysisintriguingonthepossibilitytoomitchemotherapy

! Ara,onaleforclinicaltrialsevalua,ngchemotherapy-freeregimensisprovided

PERTAIN: practical implications and future prospects


The DETECT study

PolasikOT-02-04


Prognostic significance of TILs in metastatic, HER2 positive breast cancer: analysis of the

CLEOPATRA trial

Luenetal,LancetOncolepubDec2016


TILs in subgroups



Outcome by TILs



Stromal TILs and effect of Treatment



! TILsareprognos,cinHER2posi,veearlyandmetasta,cbreastcancer

! Noprac,calclinicalimplica,ons

! Interes,nginsightsforthemechanismofac,onofdoublemonoclonalan,bodytarge,ngandpossibilitytocombinewithimmunecheckpointinhibitors

TILs in HER2 positive MBC


Brain metastases in HER2 positive MBC

ShacharP1-12-18


Single agent T-DM1and Brain Metastases

MontemurroP1-12-10


CNS regressions in patients with CNS metastases eligible for RECIST evaluation (126 patients)

MontemurroP1-12-10

-BOR21%

-CBR43%

-Reduc,on>30%inBMdiameter43%


T-DM1 ability to work in the CNS

AskoxylakisJNatlCancerInst2016


! T-DM1shallnotbeconsideredanagentofchoiceinthetreatmentofnewlydiagnosedCNSmetastases

! Itsuseisreasonableinpa,entswithtreatedandstableCNSmetastases

! T-DM1shouldbeexploredinpa,entswithCNSmetastasesfailingpriortreatments

T-DM1 and CNS metastases


Newer Strategies and Drugs

Approach Ra5onale Examples Notablefacts

Neweran,HER2ADC

Moreefficientdruginternaliza,onandrelease

MEDI7246,XMT-1522,MM302

Ac,veinHER2nega,vetumors

Poten,a,ngtheimmunologicproper,esofmoAbs

EnhancingADCCcouldbeawaytoimproveefficacy

Margetuximab,IgEhomologuesoftrastuzumab,proteaseresistantmoAbs

Clinicaltrialsareongoing

ExploringnovelTKIs MoreefficientHER-inhibi,onofTKac,vity

Nera,nib,Afa,nib,Caner,nib,AZD8931,Pozio,nib,ONT338

Maybecomeapreferredop,oninHER2-mutatedtumors

MontemurroBackFromSanAntonio2016


Neratinib in HER2-mutant BC

HymanPD2-08


Antitumor activity

HymanPD2-08


BiologicalDriverEnhancedADCC

AnchorforADC

Muta,on?

Towards a redefinition of HER2-positivity for therapeutic purposes?


PERTAIN: PFS in by stratification subgroups

ArpinoS3-04

Carcinoma della mammella HER2 positivo metastatico · Unit of Inves,gave Clinical Oncology Is,tuto di Candiolo (IRCCS) Carcinoma della mammella HER2 positivo metastatico

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