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COMPARISONOFUTILITYCOSTINTHREECOMMERCIALLYAVAILABLEPRECISIONMEDICINEAPPROACHESINONCOLOGY
KennethRussell1,JaakJanssens2,AndrewDean3,WilliamGallagher4,AlejandroHernandez1,AndreasVoss1,GordonStamp51-CarisLifeSciences,Basel,Switzerland;2-DepartmentofOncology,LimburgOncologyCenter,Belgium;3-StJohnofGodHospital,Subiaco,Australia;4-UCDSchoolofBiomolecularandBiomedicalScience,UCDConwayInsJtute,UniversityCollegeDublin,Dublin,Ireland;5-ImperialCollegeSecJonofInvesJgaJveMedicine,HammersmithCampus,London,UnitedKingdom
AbstractBACKGROUND:Theintroduc-onofmolecularprofilingasstandardofcareincancerhasledtothelaunchofanumberofcommercialprecisionmedicineservices,whichdifferlargelyintheirapproaches.Itcanbedifficultforpayers,physicians,andpa-entstodis-nguishbetweentheseservicesanddeterminewhichtes-ngismostappropriateforanindividualcase.Anunderstandingoftheclinicalu-lityandtheu-litycost(costoffindingonepa-entwithclinicalbenefit)ofthedifferentapproachescanhelptosetexpecta-onsforallstakeholdersinvolved.OBJECTIVES:Theaimofthisstudyistodefinetheu-litycostofthreeleadingcommerciallyavailableoncologyprecisionmedicineapproaches,CarisMolecularIntelligence®(CMI),Founda-onOne®andPCDx™.METHODS:Asystema-creviewofallpublishedclinicalevidenceforthethreeserviceswasperformed,todeterminethenumberofpa-entstreatedinlinewiththeprofilingresultsandtheclinicalbenefitresul-ngfromthesetreatmentchoices.U-litycostwasdefinedasthelistpricedividedbythefrac-onofpa-entstreatedbasedupontheprofilingresultsandtheclinicalbenefitintreatedpa-ents.RESULTS:Basedonthenumberofprofiledpa-entstreatedandthecorrespondingnumberofpa-entswithclinicalbenefit,34%ofCMI-profiledpa-entshadclinicalbenefit(184of534profiledpa-ents),comparedto6%ofthoseprofiledwithFounda-onOne®(166of2,675profiledpa-ents)and11%profiledusingPCDx™(19of168profiledpa-ents).U-litycostwascalculatedas$19,118forCMI,$43,636forPCDx™and$96,667forFounda-onOne®.CONCLUSIONS:Theresultsofthisstudyshowsthatthemul-plaZormapproachofCMIbringsthehighestclinicalu-lity,basedontheuseofconven-onalchemotherapiesinthemajorityofpa-entsprofiled.Alowclinicalu-litymeansthatalmost20casesofFounda-onOne®mustbepurchasedtofindonepa-entwhobenefits.
Methods–ModelforCalculaXonofUXlityCost• Clinicalu-lityisdefinedastheusefulnessofatestforclinicalprac-ceandis
dis-nctfromclinicalvalidity,whichishowwellthetestcandeterminethepresence,absence,orriskofaspecificdisease.1
• Themodelassumesthattheclinicalu-lityofamolecularprofilingapproachmustdemonstratewhethertheyleadtoareconsidera-onofthetreatmentplanandwhetherthisimprovestheclinicaloutcomeinprofiledpa-ents.
• U-litycostwasdefinedasthelistpricedividedbythefrac-onofpa-entstreatedbasedupontheprofilingresultsandtheclinicalbenefitintreatedpa-ents.
• Theu-litycostisareflec-onoftheclinicalu-lityandindicatesthecostneededtotreatonepa-entwithclinicalbenefit.
• Sta-s-calanalysis(unpairedt-tests)wasperformedusingGraphPadTM.• Listpricesfortherespec-veserviceswerebasedontelephoneenquiryor
accessedonline.2,3
Results–GraphicalRepresentaXonofClinicalUXlityin100profiledpaXents• Inahypothe-calpopula-onof100pa-ents,significantlymorepa-entsaretreated
usingCMIcomparedtoFMI(p<0.0001,95%CI0.47to0.69)orPCDx(p<0.0001;95%CI0.39to0.63).
• Therewasnosignificantdifferencebetweenpa-entstreatedwhenFMIandPCDxwereusedastheprofilingapproach(p=0.2380;955CI-0.19to0.05).
• Significantlymorepa-entsoftheoverallcohortprofiledexperienceclinicalbenefitwhenusingCMIcomparedtoFMI(p<0.0001;95%CI0.17to0.39)orPCDx(p<0.0001;95%CI0.13to0.35).
• Therewasnosignificantdifferencebetweenlevelsofprofiledpa-entswithclinicalbenefitwhenFMIandPCDxwereusedastheprofilingapproach(p=0.2995;95%CI-0.12to0.04).
StudyHighlights–UXlityCostDiffersBetweenProfilingApproaches• TheU-lityCost(orthecostofprofilingperpa-enttestedwithclinicalbenefit)
usingCMIat$19,118andislessthanaquarteroftheequivalentcostof$96,667usingFMI’sNGSonlyapproachandhalfthatofPCDX($43,636).
Results• Seventy-sevenpercent(411of534)ofpa-entsprofiledwithCMIweretreated
inlinewiththereport.Ofthese,88%(365of411)wereevaluable.Fihypercentofevaluablepa-ents(184of365)hadclinicalbenefit.Theoverallclinicalu-litywas34%(184of534profiledpa-ents).
• Nineteenpercent(499of2,675)ofpa-entsprofiledusingFMIweretreatedinlinewiththeprofilingfindings.Ofthese,98%(488of499)wereevaluable.Thirty-fourpercentofevaluablepa-ents(166of488)hadclinicalbenefit.Thisrepresentsanoverallclinicalu-lityof6%(166of2,675profiledpa-ents).
• Twenty-sixpercent(44of168)ofpa-entsprofiledusingPCDxweretreatedinlinewiththereport,ofwhomallwereconsideredevaluable.Forty-threepercentoftreatedpa-entshadclinicalbenefit,represen-nganoverallclinicalu-lityof11%(19of168profiledpa-ents).
Conclusions• Significantlymorepa-entsaretreatedusingCMI’smul-plaZorm
profilingapproach,whichprovidesthemostcomprehensiveinforma-on(onwhichchemotherapies,hormonetherapiesandimmunotherapiestouseaswellaswhichtargetedtherapiesaresuitable)comparedtothosefocusedontargetedtherapiesalone.
• Theimpactontreatmentchoiceisdirectlydependentonthepanelofbiomarkerstested,thefrequencyofthosebiomarkersinthepopula-onandthelevelofevidencepresentedtotheoncologistinsupportofachangeintreatmentdecision.
• Theindividualpa-ent’slikelihoodofclinicalbenefitwithinthewholeprofiledpa-entgroupisthemostcri-calmeasureforapa-entandtheironcologistwhenseingexpecta-onsofwhatamolecularprofilecanoffer.
• Thecostofprofilingdoesnotincludeanyconsidera-onfortherecommendedtherapies,whichwouldfurtherextendthegapincostgiventhehighpriceoftargetedtherapiescomparedtoconven-onalcytotoxicagents.
• Thevalueofprofilingshouldnotbeconsideredasareflec-onoftheunitcostbutrathertheamountthatneedstobeinvestedtobringclinicalbenefittoasinglepa-ent.
• Precisionmedicineusingasequencing-onlyapproachbringssuchlowclinicalu-litythatthecostsseemunsustainableoutsideofaresearchseing.
References1. PeabodyJW,ShimkadaR,TongKBandZubillerMB.NewThinkingonClinicalU-lity:Hard
LessonsforMolecularDiagnos-cs.AmJManagCare2014;20(9):750–756.2. Accessedonlineon16October2017at
hrps://assets.contenZul.com/vhribv12lmne/5BJHWaCe1Gwu8CaksomGS8/653f19c8657097e43fad4aabbc6495a4/Pa-ent_Informa-on_Guide_5.pdf
3. Accessedonlineon16October2017athrp://www.paradigmdx.com/wp-content/uploads/2014/08/ParadigmPCDxFAQs4-2014.pdf
Background• Moleculartumorprofilingforpa-entswithadvancedorrecurrentsolidtumorsisincreasinglyadoptedasstandardofcareinoncology,asithasbeendemonstratedthatimprovedclinicaloutcomescanresultfromselec-onoftheop-maltherapyforindividualpa-ents.
• Ini-allargescalearemptstoprofilepa-entsinthehopeofdirec-ngthemtomolecularlymatchedclinicaltrialshavehighlightedthatonlyasmallpropor-onofpa-entshaveac-onablealtera-onswhicharesuitableforenrollmentintoatrial.
• Foroncologistswhoareac-velyintegra-ngtumorprofilingintotheirpa-ent’scaretoday,itcanbechallengingtounderstandthedifferencesinclinicalu-lityandbenefitbetweennumerousavailablemolecularprofilingservices.Theohen-considerablecostsatthepa-ent’sexpenserequirejus-fica-on.
• Theaimofthisstudyistotocompareandcontrasttheclinicalu-lityof3commercialapproaches,toshowthatnotallapproachestoprecisionmedicinearethesameintermsofqualityandcost-effec-veness.
Methods• Threecommerciallyavailableserviceswereincludedinthisanalysis–Caris
MolecularIntelligence®fromCarisLifeSciences,Founda-onOne®fromRoche/Founda-onmedicine,PCDx™fromParadigm.
• KeydifferencesbetweenmolecularprofilingserviceslieintherangeandscopeofplaZormsusedtoassessbiomarkers.
• CarisMolecularIntelligence®(CMI)–mul-plaZormprofilingservicecomprisedofimmunohistochemistry(IHC),next-genera-onsequencing(NGS),RNAsequencingandinsituhybridiza-on(ISH)
• Founda-onOne®(FMI)–NGSonly• PCDx™–Mul-plaZormservicecomprisedofIHCandNGS• Acomprehensivereviewofallpublisheddatawasperformedfordetailson
numberofpa-entsprofiled,treated,evaluableandwithclinicalbenefit.• Datafromacomparisonofcommerciallyavailableserviceswasbasedon534
pa-entsprofiledaspartofphysician-ledstudiesforCMI,2675pa-entsprofiledusingFMI,and168pa-entsprofiledbyPCDx.
• Itisassumedthatpa-entswhoarenotevaluabledidnothaveclinicalbenefit.
List Price
Utility Cost
Clinical Utility
Impact on Treatment Choice
Impact on Patient Outcome
Clinical Utility
PaXentsProfiled
PaXentsTreated
%Impacton
TreatmentChoice
PaXentsEvaluableforClinicalBenefit
PaXentswithclinicalBenefit
%ClinicalBenefit
(comparedtoevaluablepa0ents)
%ClinicalUXlity
(comparedtopa0entsprofiled)
534 411 77 365 184 50 34VonHoffetal.JClinOncol(2010)28(33):4877-4883;Jamesonetal.BreastCancerResTreat(2014):147(3):579-588;Deanetal.BioMedResearchInternaJonal(2016)doi:10.1155/2016/4627214;Popovtzeretal.BioMedResearchInternaJonal(2015)doi:10.1155/2015/614845;Ramanathanetal.CancerRes(2012)72(8Suppl):AbstractnrLB-221.;Epelbaumetal.BioMedResearchInternaJonal(2015)doi:10.1155/2015/681653.;Purimetal.JournalofClinicalOncology(2017)35(15_suppl):e15537.;SeeberetalGenes&Cancer(2016):7(9-10):301-310.;ElAhmadieetal.EuropeanJournalofCancer(2015)51(supplementS3):S43.;Chahineetal.PresentedatICACT2016.;ElNahasetal.PresentedatICACT2017.
2,675 499 19 488 166 34 6Ferreiraetal.AnnOncol(2014)25(suppl4):iv560;Ganesanetal.MolCancerTher(2014)13(12):3175-84;BrandaoMoreiraetal.JournalofClinicalOncology(2015)33(28_suppl):133-133;BrandaoMoreiraetal.JournalofClinicalOncology(2015)33(28_suppl):133-133;Wheleretal.CancerRes(2016)76(13):3690-3701;Schwaederleetal.MolCancerTher(2016)15(4):743-752;Sohaletal.JNCIJNatlCancerInst(2016)108(3):doi:10.1093/jnci/djv332;Blumenthaletal.JNeurooncol(2016)130:211-219;Rodriguez-Rodriguezetal.GynecologicOncology(2016)141(1):2-9;Johnsonetal.TheOncologist(2014)19:616-622;Hirschfieldetal.TheOncologist(2016)21:1315-1325;Groisbergetal.Oncotarget(2017)8:39254-39267;Koenigetal.JClinOncol(2016)34(suppl;abstr4100);Dhiretal.CancerMed(2017)6(1):195-206;Yuanetal.Oncotarget(2017)8(16):26414-26423;Grenaderetal.AnJcancerDrugs(2016)27(9):899-907;Gundersonetal.GynecolOncol(2016)141(1):24-28;Groisbergetal.JClinOncol35(15_suppl):2582;Daltonetal.JCOPrecisionOncology(2017)1:1-19;Hodeibetal.GynecologicOncology(2017)145(1_suppl):212;Sicklicketal.JClinOncol35,2017(suppl;abstr2512);Bryceetal.Oncotarget(2017)8(16):27145-27154;Braitehetal.JClinOncol(2014)32:5s(suppl;abstr11109);DiBardinoetal.ClinicalLungCancer(2016)17(6):517-522;Mantripragadaetal.JournalofOncologyPracJce(2016)12(4):e396-e404
168 44 26 44 19 43 11Radovichetal.Oncotarget(2016)doi:10.18632/oncotarget.10606
100 100 100
77
19
26
34
611
Pa-entsProfiled Pa-entsTreated Pa-entsTreatedwithClinicalBenefit
A B C A B C A B C
A B C
IntentToTreat=100 IntentToTreat=100 IntentToTreat=100
Treated=77
Treated=19
Treated=26
TreatedwithClinicalBenefit=34TreatedwithClinicalBenefit=6
TreatedwithClinicalBenefit=11
ServiceListPrice($)
PercentageofPaXentsTreated
CostperPaXentTreated
($)
PercentageClinicalUXlity
UXlityCost($)
CarisMolecularIntelligence® $6,500 77 $8,442 34 $19,118
FoundaXonOne® $5,800 19 $30,526 6 $96,667
PCDx™ $4,800 26 $18,462 11 $43,636
$6'500 $5'800 $4'800$8'442
$30'526
$18'462$19'118
$96'667
$43'636Cost($
)
ListPrice
CostPerPa-entTreated
U-lityCost
A B C A B C A B C
A
B
C
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