维持治疗的分子靶标作用

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1、PhilipC.Mack,PhDAssociateAdjunctProfessorUCDavisCancerCenterHowdoweperformmoreeffectivebiomarkertestingformatchingNSCLCpatientswithoptimaltherapyformaintenanceofdiseaseremissionandafterrelapsedNSCLC?Apatienthasbenefitedfromtreatment(tumorresponseordurablestabledisease)Ho

2、wcanweusebiomarkerstohelp:1)Maintainarespondingpatientinadiseasecontrolstate?2)Restorearelapsingpatienttoadiseasecontrolstate?Whatbiologicinformationisavailable?BaselinespecimensAcquiredpriortopreviousinterventionsDiagnosticFFPEspecimen?Biomarkerinfoobtained?Baselinebloo

3、ddraw?Post-progressionspecimensAcquireduponprogressionfollowingmeaningfulbenefitSecondbiopsy?Serialblooddraws?ErlotinibPemetrexedBevacizumabDocetaxelGemcitabineMaintenanceTherapyOptionsMaintenanceTherapyOptionsandAssociatedBiomarkersErlotinib–EGFRmutationspredictresponse

4、Evidence:High,wellaccepted,standard-of-carePemetrexed–HighTSpredictresistanceEvidence:Strong,requiresadditionalvalidationoverhistologyBevacizumab–NoacceptedmarkersforbenefitConjecture:Possibilityofmarkersofacquiredresistance?Docetaxel–BetatubulinIIImutations/expressionle

5、velsEvidence:Weak,requiresextensivefurtherinvestigationGemcitabine–HighRRM1levelspredictresistanceEvidence:IntriguingbutcontroversialBiomarkerstrategiesfor“Continuous”maintenancetherapyi.e.pemetrexedmaintenanceinplatinum+pem-treatedpatientwithCR,PRorSDNobiomarkerscurrent

6、lyapplicableBiomarkersshouldbeusedtoaidfront-linedecision-makingSuccessoffront-linetherapyischiefindicatorforutilityofcontinuousmaintenancestrategiesCurrentresearcheffortsfocusedonidentificationofemergentresistancemarkersBiomarkerstrategiesfor“Switch”maintenancetherapyi.

7、e.erlotinibmaintenanceincarbo/pac-treatedpatientwithCR,PRorSDEstablishedbiomarkerswillberelevantBiomarkerspredictiveofbenefitfromanagentwouldbeexpectedtobeofutilityformaintenanceoptionsNote:ClinicalevidenceandgeneralconsensusamongexpertsisthatpatientsshouldreceiveFRONT-L

8、INEtreatmentof:erlotinibforEGFRmutanttumorscrizotinibforEML4-ALKpositivetumors56-year-oldCaucasianfemal