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PhilipC.Mack,PhDAssociateAdjunctProfessorUCDavisCancerCenterHowdoweperformmoreeffectivebiomarkertestingformatchingNSCLCpatientswithoptimaltherapyformaintenanceofdiseaseremissionandafterrelapsedNSCLC?Apatienthasbenefitedfromtreatment(tumorresponseordurablestabledisease)Howcanweusebiomarkerstohelp:1)Maintainarespondingpatientinadiseasecontrolstate?2)Restorearelapsingpatienttoadiseasecontrolstate?Whatbiologicinformationisavailable?BaselinespecimensAcquiredpriortopreviousinterventionsDiagnosticFFPEspecimen?Biomarkerinfoobtained?Baselineblooddraw?Post-progressionspecimensAcquireduponprogressionfollowingmeaningfulbenefitSecondbiopsy?Serialblooddraws?ErlotinibPemetrexedBevacizumabDocetaxelGemcitabineMaintenanceTherapyOptionsMaintenanceTherapyOptionsandAssociatedBiomarkersErlotinib–EGFRmutationspredictresponseEvidence:High,wellaccepted,standard-of-carePemetrexed–HighTSpredictresistanceEvidence:Strong,requiresadditionalvalidationoverhistologyBevacizumab–NoacceptedmarkersforbenefitConjecture:Possibilityofmarkersofacquiredresistance?Docetaxel–BetatubulinIIImutations/expressionlevelsEvidence:Weak,requiresextensivefurtherinvestigationGemcitabine–HighRRM1levelspredictresistanceEvidence:IntriguingbutcontroversialBiomarkerstrategiesfor“Continuous”maintenancetherapyi.e.pemetrexedmaintenanceinplatinum+pem-treatedpatientwithCR,PRorSDNobiomarkerscurrentlyapplicableBiomarkersshouldbeusedtoaidfront-linedecision-makingSuccessoffront-linetherapyischiefindicatorforutilityofcontinuousmaintenancestrategiesCurrentresearcheffortsfocusedonidentificationofemergentresistancemarkersBiomarkerstrategiesfor“Switch”maintenancetherapyi.e.erlotinibmaintenanceincarbo/pac-treatedpatientwithCR,PRorSDEstablishedbiomarkerswillberelevantBiomarkerspredictiveofbenefitfromanagentwouldbeexpectedtobeofutilityformaintenanceoptionsNote:ClinicalevidenceandgeneralconsensusamongexpertsisthatpatientsshouldreceiveFRONT-LINEtreatmentof:erlotinibforEGFRmutanttumorscrizotinibforEML4-ALKpositivetumors56-year-oldCaucasianfemale,never-smoker,presentswithcoughAbnormalCXR&CTscan:RULmass,multiplenodules,liverandbonymetastases.FNAofRULmass:adenocarcinoma,TTF1+KPS=90%;MRIbrain:negativeformetsCaseExample:56FNeversmokerPatientreceives4cyclesofcarboplatin/paclitaxelplusbevacizumab.RECISTBestResponse:partialresponseCoughresolved,otherwiseasymptomaticafter4cyclesCaseExample:56FNeversmokerCaseExample:56FNeversmoker2ndlineMaintenanceYourpathologistdeterminesthatthereissufficienttumormaterialformoleculartesting:TumorisfoundtobeEGFR-mutation-positive(Exon19deletion).Atthispointdoyou:34%38%24%4%A.“watchandwait”withCTscansevery2-3months,thenuseerlotinibatprogressionB.Continuewithbevacizumabuntilprogression,thenuseerlotinibC.StopbevacizumabandswitchtoerlotinibmaintenancetherapyD.Continuebevacizumab,adderlotinibformaintenancetherapySATURN:phaseIII,placebo-controlledtrialofmaintenanceerlotinib-EGFRmutationstatusIntention-to-treatpopulationEGFRmutant-positivepopulationThissubgroupbyfarshowedthemostbenefitSATURNTrialfindingsTheSATURNtrialshowedthaterlotinib,givenasmaintenanceimmediatelyafterastandardfirst-lineplatinum-basedchemotherapy,significantlyimprovedtheoutcomeofmNSCLCSignificantlyimprovedPFSwasnotedintheentireintent-to-treatpopulation,includi...