efficacy and safety of testosterone in metasta3c renal cell ... 1...testosterone undecanoate* +...
TRANSCRIPT
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