endocrine therapy-induced alopecia (eia) · 2018. 7. 11. · ecdf* of hair loss post therapy 0 6 12...
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EndocrineTherapy-InducedAlopecia(EIA)
MarioELacoutureMDMember,MemorialHospitalDirector,OncodermatologyProgramNewYork,NY
• Researchfunding– Berg,BMS,Genentech/Roche,RJRFund,Galderma,Paxman,Novartis
Disclosures
• Consulting/Advisory– Legacy,Novartis,Janssen,BMS,Genentech/Roche,Galderma,Debio,Pfizer,
Helsinn,SilkTherapeutics,Foamix,BoehringerIngelheim,MedischeVoet
EndocrineTherapyinBreastCancer
AliandCoombes,NatRevCancer2002
Puglisietal,AnnInternMed2001;Rossietal,AnnOnc2013
Yipetal,BrJDermatol2009,2012
HormonesandHair-DangerousLiasions
Ohnemusetal,EndocrineRev2006;Brough,IntJWomensDerm2017
Saggaretal,Oncologist2013;Hillmanetal,BrJDermatol2012;Galliccioetal,BrCancerResTreat2013;Rossietal,AnnOnc2013
HairsafterAI/Tamoxifen
EndocrineTherapy-InducedAlopecia(EIA)
Estrogen(notTestosterone)isGoodforHair
Estradiol+Spironolactone
Adenugaetal,JAAD2012
Saggaretal,Oncologist2013;Parketal,AnnDermatol2014;Galliccioetal,BrCancerResTreat2013;Lindneretal,BrJDermatol2012
EndocrineTherapy-InducedAlopecia(EIA)
Tamoxifen1yr
• SERMs,Aromataseinhibitors
• Metaanalysis(n=13,145):4.4%• Survey(n=868):31.8%
Anastrozole3yrs
CHANCE:AProspective,LongitudinalStudyofChemotherapy-InducedHair,SkinAndNailChangesinWomenwithBreastCancer
ClinicalTrials.govIdentifier:NCT02530177
TherapyInit Eval Eval Eval Eval Eval Studyend
Yr0 Yr1 Yr2 Yr3
• ThatIwillpermanentlylosemyhairfromchemotherapyorwithhormones?– Primaryendpoint:Incidence/severityofpermanentCIAorHTIA
Globalalopecia
CHANCE:AProspective,LongitudinalStudyofChemotherapy-InducedHair,SkinAndNailChangesinWomenwithBreastCancer
ClinicalTrials.govIdentifier:NCT02530177
TherapyInit Eval Eval Eval Eval Eval Studyend
Yr0 Yr1 Yr2 Yr3
• ThatIwillpermanentlylosemyhairfromchemotherapyorwithhormones?– Primaryendpoint:Incidence/severityofpermanentCIAorHTIA
Hairnumber/diameter
Alopecia TamoxifencohortN=21(%)* AromataseinhibitorcohortN=20(%)
CTCAEv4.03 Baseline Follow-up Baseline Follow-up
Grade0(noalopecia) 14(66.7) 6(28.6) 11(55) 8(40)
Grade1(<50%ofhairloss) 7(33.3) 15(71.4) 7(35) 11(55)
Grade2(>50%ofhairloss) 0 0 1(5) 1(5)
Trichoscopydata Baseline Follow-up Baseline Follow-up
HairshaftNpercm2 199(36.51) 190.4(33.49) 171.9(45) 171.4(51.9)
Hairthickness(microns) 70(10) 70(10) 70(10) 70(10)
CHANCEstudy(DatacutoffDecember2017)
Lacoutureetal,ASCOAnnualMeeting2018
CHANCEstudy(DatacutoffDecember2017)
Skindisordersayearafterfollow-up
TamoxifencohortN=21(%) AromataseinhibitorcohortN=20(%)
Eyelashalopecia(anygrade) 3(14.3) 2(10)
Eyebrowalopecia(anygrade) 2(9.5) 2(10)
Naildisorders* TamoxifencohortN=17(%) AromataseinhibitorcohortN=16(%)
Naildiscoloration(Grade1) 6(35.3) 7(43.8)
Nailridging 8(47) 10(62.5)
Nailloss 0(0) 0(0)
Paronychia 0(0) 0(0)
Lacoutureetal,ASCOAnnualMeeting2018
0.2
.4.6
.81
ECDF
* of h
air l
oss
post
ther
apy
0 6 12 18 24 30 36 42 48 54 60 66 72Months on therapy
* ECDF: empirical cumulative distribution function
Timetoalopeciadevelopment(n=72)
Freites-Martinezetal,JAMADermatol2018
Freites-Martinezetal,JAMADermatol2018
QualityofLifen=52
HairShaftDiameter(n=82)
Post-ChemotherapyAlopecia:pCIAorEIACBaselinecharacteristics pCIANo.(%)(n=98) EIACNo.(%)(n=94) P
Medianage 56.5(18-83years) 56(29-84years) .90
Phenotype Patternalopecia(Androgeneticalopecia-likepattern)
44(59) 69(75) .04
Diffusealopecia 31(41) 23(25)
AlopeciaseveritybyCTCAEv4.0
Grade1 46(61) 80(87) <.001
Grade2 29(39) 12(13)
Eyebrow/eyelashesalopecia 28(37) 26(28) .25
Trichoscopycharacteristics No.(SD)(n=45)(46)
No.(SD)(n=62)(66)
Hairshaftdiameter(microns) 62 68 .02
Hairdensity(percm2) 104(48) 116(35) .14
Meanhairperfollicularunit 1.3 1.5 <.001
Freites-Martinezetal(unpublisheddata)
Post-ChemotherapyAlopecia:pCIAorEIAC
Freites-Martinezetal(unpublisheddata)
*49
33 30
23
17
45
2926
21 22
30
29
0
10
20
30
40
50
Emotions Self-confidence Functioning Stigmatization Symptoms
Nor
mal
ized
Hai
rdex
scor
e(p
ossi
ble r
ange
: 0-1
00)
pCIA (n = 41) EIAC (n = 58) pCIA Mean EIAC Mean
Post-ChemotherapyAlopecia:pCIAorEIAC
pCIA EIAC
Wonetal,DermatolTher2017;Brough,IntJWomensDerm2017
AlopeciaManagementMinoxidil2%
Finasteride2.5mg
AndrogenInhibitionforAlopecia
Wonetal,DermatolTher2018
Finasteride2.5mg24weeks
Brough,IntJWomensDerm2017
AlopeciaManagementAlgorithm
Tamoxifen,39y/o Tamoxifen+Minoxidil
Freites-Martinezetal,JAMADermatol2018
Anastrozole,72y/o
Anastrozole+Minoxidil+Spironolactone
Freitesetal,2017Freites-Martinezetal,JAMADermatol2018
ETALManagement-ClinicalOutcomeLetrozole,66y/o
Letrozole+Minoxidil
Freites-Martinezetal,JAMADermatol2018
26%
50%
24%
0%
10%
20%
30%
40%
50%
60%
NoImprovement ModerateImprovement SignificantImprovement
Minoxidil5%(n=46)
Freites-Martinezetal,JAMADermatol2018
Anastrozole,72y/o Anastrozole+Minoxidil+Spironolactone
Follicles:28HSdiameter(avg):82
Follicles:35HSdiameter(avg):89
Freites-Martinezetal,JAMADermatol2018
-20
0
20
40
60
80
100
120
-20
0
20
40
60
80
100
120
Terminalhairdensity Vellushairdensity Hairshaft diameter
Diam
eter(M
icron
s)
Density
(num
bero
fhairs)
Baseline
Follow-up
Difference
PatientsonAI/Tam(n=41)
P<0.05
P<0.05
Freites-Martinezetal,JAMADermatol2018
• Endocrinetherapiesfrequentlyresultinalopecia
• ImpactonQoLsignificant
• Severityusuallyisgrade1(mild)andrespondstominoxidilandspironolactone
• EIAwillincreaseinimportance
Longeradjuvanttherapyandincreasedsurvival
DecreasedincidenceofCIAwithnoveltherapies
TrialsforEIA
EndocrineTherapy-InducedAlopecia(EIA):Conclusions
