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.

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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