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EthicalChallengesinPrecisionPediatricOncology
StevenJoffe,MD,MPHEmanuelandRobertHartAssociateProfessorDepartmentofMedicalEthics&HealthPolicy
CoaliDonAgainstChildhoodCancerAnnualMeeDngChildren’sHospitalofPhiladelphia
June22,2016
Thevisionofprecisioncancermedicine“Asthecostofsequencingdrops,whole-genomegermline,tumor,andRNAsequencingwill…usherinaneweraofunprecedentedcomprehensiveanalysisofthegenomeforallchildrenwithhigh-risk,refractory,orrelapsedcancers—anecessaryfirststeptothedemonstraDonoftheclinicaluDlityandvalidityofgenome-basedprecisiontherapy.“a
2 JAMAOncol.2016Jan28.doi:10.1001/jamaoncol.2015.5685.
Thevisionofprecisioncancermedicine“Asthecostofsequencingdrops,whole-genomegermline,tumor,andRNAsequencingwill…usherinaneweraofunprecedentedcomprehensiveanalysisofthegenomeforallchildrenwithhigh-risk,refractory,orrelapsedcancers—anecessaryfirststeptothedemonstraDonoftheclinicaluDlityandvalidityofgenome-basedprecisiontherapy.“
3 JAMAOncol.2016Jan28.doi:10.1001/jamaoncol.2015.5685.
Fourethicalchallenges
• PosiDvebalanceofbenefitsoverharms• Informeddecision-making
• EquitabledistribuDonofbenefits• Ge^ngfromheretothere
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Ensuringbenefitsoverharms
• PotenDalbenefitsoftargetedapproach– Longerlife– Beberqualityoflife– AvoidanceofineffecDvetherapies
• PotenDalharmsoftargetedapproach– MisinterpretaDonofvariantsintumorgenome– Useoftherapiesbasedoninference,notevidence– Financialtoxicity
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Financialtoxicity:thecostsofprecisioncancertherapy
Drug DiseaseSurvivalgaininmonths(median)
Typicalcostoftreatmentcourse($)
nab-Paclitaxel
MetastaDcbreast 2.2 26000
Lung 1 30000
Pancreas 1.8 27000
ErloDnibLung 3.4 52000
Pancreas 0.4 22000
CetuximabHead&neck(locallyadvanced) 20 14000
Head&neck(metastaDc) 2.8 43000
HercepDnBreast(localized) 24 65000
Breast(metasDaDc) 4.8 54000
6 JAMA312:1629,2014
Financialtoxicity:thecostsofprecisioncancertherapy
Drug DiseaseSurvivalgaininmonths(median)
Typicalcostoftreatmentcourse($)
nab-Paclitaxel
MetastaDcbreast 2.2 26000
Lung 1 30000
Pancreas 1.8 27000
ErloDnibLung 3.4 52000
Pancreas 0.4 22000
CetuximabHead&neck(locallyadvanced) 20 14000
Head&neck(metastaDc) 2.8 43000
HercepDnBreast(localized) 24 65000
Breast(metasDaDc) 4.8 54000
7 JAMA312:1629,2014
Financialtoxicity:thecostsofprecisioncancertherapy
Drug DiseaseSurvivalgaininmonths(median)
Typicalcostoftreatmentcourse($)
nab-Paclitaxel
MetastaDcbreast 2.2 26000
Lung 1 30000
Pancreas 1.8 27000
ErloDnibLung 3.4 52000
Pancreas 0.4 22000
CetuximabHead&neck(locallyadvanced) 20 14000
Head&neck(metastaDc) 2.8 43000
HercepDnBreast(localized) 24 65000
Breast(metasDaDc) 4.8 54000
8 JAMA312:1629,2014
Financialtoxicity:thecoststopaDentsandfamilies
9hbps://www.washingtonpost.com/news/wonk/wp/2016/04/08/cancers-sinister-
side-effect-financial-toxicity/
Intheageof$10,000-a-monthcancerdrugsandhealthplansthatshikmoreofthecostofhealthcareontopaDents,researchsuggestswe'vebeenunderesDmaDngoneofcancer'srealharms:“financialtoxicity.”
Financialtoxicity:thecoststopaDentsandfamilies
10hbps://www.washingtonpost.com/news/wonk/wp/2016/04/08/cancers-sinister-
side-effect-financial-toxicity/
A2013study…foundthatnearlyhalfofcancerpaDentswithinsurancesurveyedcutbackontheirspendingonfoodandclothingordippedintosavingstopayfortheirtreatment.ThemajoritycutbackonleisureacDviDes.Three-quartersofthemreceivedfinancialassistancewiththeirdrugcopayments.
Ensuringbenefitsoverharms
• PotenDalbenefitsofgermlinesequencing– Shedlightonchild’sriskoffuturecancers– InformtherapeuDcchoices(e.g.,avoidradiaDon)– InformfamiliesaboutcancerriskamongrelaDves
• PotenDalharmsofgermlinesequencing– MisleadinginformaDonaboutfuturegeneDcrisk– TestresultswithuncertainimplicaDonsforintervenDon
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SupporDnginformeddecisionmaking
• Withrespecttotumorsequencing– Choosingamongtherapiesbasedonweakevidence,oroninferencealone
– BalancingacDvetreatmentvs.palliaDvecare
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SupporDnginformeddecisionmaking
• Withrespecttogermlinesequencing– EducaDngpaDents,families(andoncologists)aboutinheritedcancerrisk
– Ensuringinformedchoicesabouttreatment&screening
– SupporDnginformedchoicesaboutreturnofsecondary(non-cancer)geneDcriskfindings
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EnsuringequitabledistribuDonofbenefits
• HighcostsoftargetedcancertherapiesmayblockaccessforsomepaDents– InU.S.&otherdevelopedcountries– Inlow-&middle-incomecountries
• Companies’focusonlargeradultmarketsmaystrandkidsintherapeuDcorphanhood
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Togetfromheretothere,weneed…
• Commitmenttoevidence-basedprecisionpediatriconcology– ValidaDonthattargeDngavariantimprovesquanDty&/orqualityoflife
– RejecDonoftreatmentparadigmbasedonweakevidenceoroninferencealone
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Togetfromheretothere,weneed…
• Advocacyforclinicaltrialsofprecisionapproachinpediatriconcology– ToovercomestaDsDcal&methodologicalchallengesofresearchonever-smallergroups
– Toovercomemarket-baseddisincenDvestotesDngprecisiondrugsandapproachesinchildrenwithcancer
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Acknowledgments
• Dana-FarberCancerInsDtuteCanSeqteam– LeviGarraway,MD,PhD– StacyGray,MD,AM
• NHGRI&NCI(U01HG006492)
[email protected]:@SteveJoffe
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