晚期大肠癌的个体化治疗

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1、IndividualizedTreatmentsforAdvancedColorectalCancer:TheKRASStoryDavidZ.Chang,MD,PhDUTMDAndersonCancerCenter张宗圣CSCOAnnualMeeting2008SUMMARYTargetedtherapieshaveimprovedclinicaloutcomeofmCRCNeedjudicioususeoftheseagents:when,howManyquestionsremainingHowtoovercomethehighcost►Treatmentsneedtobeindiv

2、idualized:biomarkersandgeneticsignaturesStoryforGIatASCO20081stbiomarkerforindividualizedtherapyforcolorectalcancer:KRASstatuspredictsresponsiveness(orlackofresponsiveness)toEGFRtargetedtherapiesAdvancesintheTreatmentofColorectalCancer198019851990199520002005CapecitabineOxaliplatinCetuximabBevac

3、izumabIrinotecan5-FUPanitumumabMedianSurvivalBSC:4-6months5FU:10-14months5FU/OX/Iri:~20months+targetedtherapy:>30months?SomeHistoricalDataEGFRTargetedTherapiesinCRCCetuximab&PanitumumabBOND1:RandomizedPivotalTrialinMetastaticColorectalCancerRANDOMIZECetuximab+irinotecanCetuximab(initialdose,

4、400mg/m2thenweeklyinfusion250mg/m2)+irinotecan(sameasprestudytherapy)(n=218)N=329PatientswithmCRCwhoprogressedduringorwithin3moafteririnotecanEGFR+CRCHistaminereceptorantagonistpremedicationgivenbeforeatleastthefirstcetuximabinfusion.Cetuximab(initialdose,400mg/m2thenweeklyinfusion250mg/m2)(n=11

5、1)CunninghamD,etal.NEnglJMed.2004;351:337-345.0510152025012345622.9%5.7mo4.2mo10.8%ObjectiveResponseRateMedianDurationofResponseCetuximabwithirinotecan(n=218)Cetuximabasasingleagent(n=111)CetuximabRandomizedPivotalTrial:ResponseRatesP=0.007CunninghamD,etal.NEnglJMed.2004;351:337-345.RANDOMIZEN=

6、1298PatientswithCRCwhoprogressedon5FU,Oxaliplatin,GFR+IrinotecanCetuximab+IrinotecanJonkeretal.AACR2007.Abstract3556.EPIC:Cetuximab+IrinotecanvsIrinotecanas2nd-lineTherapyEPICStudyEfficacyDataCetuximabisactivein2ndline,irinotecannaïveptsLackofoverallsurvival:cross-overeffect?CRYSTAL:PhaseIIITria

7、lofFOLFIRI+/-CetuximabinFirst-linemCRCRANDOMIZEFOLFIRI+cetuximab(608)First-linemCRCFOLFIRI(609)CutsemetaI,etal.ASCO2007.4000.CRYSTALEfficacyDataCetuximab+FOLFIRI(N=608)Irinotecan(N=609)PValuePFS8.98<0.036ResponseRate(%)46.9%