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
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Current treatment choices
Chemotherapyalone?(FM)
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Efficacy resutls of PERUSE
BachelotP4-21-04
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Exposure to neo/adjuvant treatments
BachelotP4-21-04
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Docetaxel or Paclitaxel with trastuzumab and pertuzumab?
BachelotP4-21-04
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Docetaxel or Paclitaxel with trastuzumab and pertuzumab?
BachelotP4-21-04
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
First line therapy with Trastuzumab and pertuzumab + AIs in patients with HER2-positive/HR positive tumors
ArpinoS3-04
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
PERTAIN: Primary End-Point
ArpinoS3-04
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
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
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
! Safe(anduseful)toaddmaintenanceendocrinetherapywithanaromataseinhibitoraEerchemotherapy.
! Resultsofthestra,fica,onsubgroupsanalysisintriguingonthepossibilitytoomitchemotherapy
! Ara,onaleforclinicaltrialsevalua,ngchemotherapy-freeregimensisprovided
PERTAIN: practical implications and future prospects
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
The DETECT study
PolasikOT-02-04
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Prognostic significance of TILs in metastatic, HER2 positive breast cancer: analysis of the
CLEOPATRA trial
Luenetal,LancetOncolepubDec2016
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
TILs in subgroups
Luenetal,LancetOncolepubDec2016
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Outcome by TILs
Luenetal,LancetOncolepubDec2016
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Stromal TILs and effect of Treatment
Luenetal,LancetOncolepubDec2016
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
! TILsareprognos,cinHER2posi,veearlyandmetasta,cbreastcancer
! Noprac,calclinicalimplica,ons
! Interes,nginsightsforthemechanismofac,onofdoublemonoclonalan,bodytarge,ngandpossibilitytocombinewithimmunecheckpointinhibitors
TILs in HER2 positive MBC
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Brain metastases in HER2 positive MBC
ShacharP1-12-18
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Single agent T-DM1and Brain Metastases
MontemurroP1-12-10
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
CNS regressions in patients with CNS metastases eligible for RECIST evaluation (126 patients)
MontemurroP1-12-10
-BOR21%
-CBR43%
-Reduc,on>30%inBMdiameter43%
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
T-DM1 ability to work in the CNS
AskoxylakisJNatlCancerInst2016
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
! T-DM1shallnotbeconsideredanagentofchoiceinthetreatmentofnewlydiagnosedCNSmetastases
! Itsuseisreasonableinpa,entswithtreatedandstableCNSmetastases
! T-DM1shouldbeexploredinpa,entswithCNSmetastasesfailingpriortreatments
T-DM1 and CNS metastases
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
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
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Neratinib in HER2-mutant BC
HymanPD2-08
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
Antitumor activity
HymanPD2-08
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
BiologicalDriverEnhancedADCC
AnchorforADC
Muta,on?
Towards a redefinition of HER2-positivity for therapeutic purposes?
DirezioneOncologiaClinicaInves2ga2va,IRCCCandiolo
PERTAIN: PFS in by stratification subgroups
ArpinoS3-04