晚期大肠癌的个体化治疗.ppt

IndividualizedTreatmentsforAdvancedColorectalCancer:TheKRASStoryDavidZ.Chang,MD,PhDUTMDAndersonCancerCenter张宗圣CSCOAnnualMeeting2008

SUMMARYTargetedtherapieshaveimprovedclinicaloutcomeofmCRCNeedjudicioususeoftheseagents:when,howManyquestionsremainingHowtoovercomethehighcost?Treatmentsneedtobeindividualized:biomarkersandgeneticsignatures

StoryforGIatASCO20081stbiomarkerforindividualizedtherapyforcolorectalcancer:KRASstatuspredictsresponsiveness(orlackofresponsiveness)toEGFRtargetedtherapies

AdvancesintheTreatmentofColorectalCancer198019851990199520002005CapecitabineOxaliplatinCetuximabBevacizumabIrinotecan5-FUPanitumumabMedianSurvivalBSC:4-6months5FU:10-14months5FU/OX/Iri:~20months+targetedtherapy:30months?

SomeHistoricalData

EGFRTargetedTherapies

inCRC

CetuximabPanitumumab

BOND1:RandomizedPivotal

TrialinMetastaticColorectalCancerRANDOMIZECetuximab+irinotecanCetuximab(initialdose,400mg/m2thenweeklyinfusion250mg/m2)+irinotecan(sameasprestudytherapy)(n=218)N=329PatientswithmCRCwhoprogressedduringorwithin3moafteririnotecanEGFR+CRCHistaminereceptorantagonistpremedicationgivenbeforeatleastthefirstcetuximabinfusion.Cetuximab(initialdose,400mg/m2thenweeklyinfusion250mg/m2)(n=111)CunninghamD,etal.NEnglJMed.2004;351:337-345.

0510152025012345622.9%5.7mo4.2mo10.8%ObjectiveResponseRateMedianDurationofResponseCetuximabwithirinotecan(n=218)Cetuximabasasingleagent(n=111)CetuximabRandomizedPivotal

Trial:ResponseRatesP=0.007CunninghamD,etal.NEnglJMed.2004;351:337-345.

RANDOMIZEN=1298PatientswithCRCwhoprogressedon5FU,Oxaliplatin,GFR+IrinotecanCetuximab+IrinotecanJonkeretal.AACR2007.Abstract3556.EPIC:Cetuximab+IrinotecanvsIrinotecanas2nd-lineTherapy

EPICStudyEfficacyDataCetuximabisactivein2ndline,irinotecanna?veptsLackofoverallsurvival:cross-ov