EfficacyandSafetyofTestosteroneinMetasta3cRenalCellCarcinomaPa3entswithFa3gue:Mul3center

RandomizedPhase2Study(FARETES)

IlyaTsimafeyeu,RuslanZukov,PavelBorisov,AnastasiaBondarenko,Kris3naZakurdaeva,YuliaTishova

KidneyCancerResearchBureau,Moscow

V.F.Voino-YasenetskyKrasnoyarskStateMedicalUniversity,

Krasnoyarsk

CityClinicalOncologyCenter,St.Petersburg

I.M.SechenovFirstMoscowStateMedicalUniversity,Moscow

RakFond,Moscow

RUDNUniversity,Moscow

Faculty Disclosure

ConsulGngandadvisoryrole:Bristol-MyersSquibb,Eisai,NovarGs,Pfizer

Travelgrant:Biocad

•  FaGgue is a frequent symptom of metastaGc renal cell carcinoma

(mRCC), and most common adverse event of treatment with

tyrosinekinaseinhibitorsandcheckpointinhibitors

BACKGROUND

Compound/Study Allgrades 3-4grades

Lenva3nib+EverolimusMotzeretal.LancetOncol.2015

59% 14%

Cabozan3nibChoueirietal.NEJM2015

56% 9%

Suni3nibMotzeretal.JCO2009

54% 11%

Axi3nibMotzeretal.LancetOncol.2013

37% 10%

Nivolumab+IpilimumabMotzeretal.NEJM2018

37% 4%

NivolumabMotzeretal.NEJM2015

33% 2%

EverolimusMotzeretal.Cancer2010

31% 5%

PazopanibSternbergetal.EJC2013

20% 2%

•  TheaimofthismulGcenterrandomizedphase2studywasto

determineefficacyandsafetyoftestosteroneundecanoatein

mRCCpaGentswithfaGguedevelopedduringtargetedtherapy

FARETESSTUDY

STUDYDESIGN

• mulGcenterrandomizedphase2studyFARETES,N=60

TESTOSTERONEUNDECANOATE*+

TARGETEDTHERAPY

R

a

n

d

o

m

i

z

a

t

i

o

n

Malepa3entwith:- clearcellmRCC

- normalPSAlevel

- lowtestosteronelevel(<12.1nmol/L)

- noevidenceofhypothyroidism

- faGgueassideeffectoffirst-linesuniGnibor

pazopanib

TARGETEDTHERAPY

1:1

*Nebido®,1,000mg,wasinjectedintramusculardeeplyon

Day1ofanewtreatmentcycle

ENDPOINTS

Primaryendpoint:differenceinmeanchangeoffaGgueaccordingtoFuncGonal

AssessmentofChronicIllnessTherapy-FaGgue(FACIT-FaGgue)

Secondaryendpoints:safety

FKSI-19score,

testosteroneserumconcentraGons,

redbloodcellscount

hemoglobinlevel

Exploratoryendpoints:DuraGonofTT,ORR,PFS,OS

Assessments:TheassessmentswereperformedatbaselineandDay28ofa

treatmentcycle

RESULTS(1):PATIENTCHARACTERISTICS&TOXICITY

•  Rateofhypogonadismwas75.6%(62from82screenedpaGents)

•  TestosteronewaswelltoleratedinmRCCpaGents

•  Nounexpectedandgrade2-4toxicitywasobserved

Tgroup,N=30

Controlgroup,N=30

Age(years),mean(range) 52(33-71) 55(42-69)

SuniGnib,N(%) 28(93) 28(93)

Pazopanib,N(%) 2(7) 2(7)

IMDCpoorriskfactors,0-2,N(%) 21(70) 22(73)

Previousnephrectomy,N(%) 30(100) 30(100)

Pa3entcharacteris3cs

RESULTS(2):FACIT-F

•  Сhangefrombaselineinthefa3guescoreontheFunc3onalAssessmentofChronicIllnessTherapy–Fa3gue(FACIT-Fa3gue)ques3onnaire

Scoringisbasedonascalefrom0to52,withlowerscoresindicaGnglessfaGgue

Thecurrentstudydidachieveits

primaryendpointbasedonthe

significantdifferencesfavored

Testosteroneovertargetedtherapy

aloneregardingfaGgue(P=0.012)

RESULTS(3):NCCN-FACTFKSI-19

•  Changefrombaselineinthefa3guescoreontheNCCN/Func3onalAssessmentofCancerTherapy(FACT)-KidneySymptomIndex19(NCCN-FACTFKSI-19)ques3onnaire(Ver.2)

Scoringisbasedonascalefrom0to76,withlowerscoresindicaGnglessfaGgue

Thehealth-relatedquality-of-life

scoresintheTestosteronegroupwere

benerthanthoseinthecontrolgroup

(P=0.01)

RESULTS(4):TESTOSTERONE,RBC,HB

•  Testosteroneserum

concentraGonwassignificantly

higherontheDay28(P=0.029)

•  Therewasnon-significant

posiGvetrendinRBCcountand

hemoglobinlevelbetween2

groups

RESULTS(5):EXPLORATORYENDPOINTS

•  Atdatacutoff(June20,2018),median(range)follow-upwas11.2(7.8

-14.6)mo

•  Objec3veresponserate:

-46.7%(14/30)including1CRand13PRsintheTestosteronearm

-33.3%(10/30)includingallPRsintheControlarm(P=0.3)

•  Mediandura3onoftargetedtherapy(fromthestartoffirst-line):

-wasnotreachedforTestosterone

-was8.3(95%CI7-9.6)moforTargetedtherapyalone

•  Discon3nua3onduetoSU/PAZ-relatedadverseeventswasoccurredin3%(1/30)ofpaGentsintheTestosteronegroupandin17%(5/30)of

paGentsintheControlgroup

•  MedianPFSandOShasnotbeenreachedinbotharms

CONCLUSIONS

• MalepaGentswithmRCCreceivingtargetedtherapyhadsignificantlylessfaGgueandbenersymptomcontrolwithTestosterone

• Testosteronetherapywassafe

• TestosteronecanprolongtheduraGonoftargetedtherapy

• PFSandOSwillbereported