27.2018-12-4-2018非小细胞肺癌EGFR突变：优化患者管理

CáncerdepulmónnomicrocíticoEGFRmutado:OptimizacióndelmanejodelpacienteManuelCoboDolsOncologiaMédicaHRegionalUniversitarioMálaga.IBIMA12-4-2018EGFRTKIsversusChemotherapyEvents/NMedianPFS(95%CI)12mPFS(95%CI)All57/10913.8m(10.3-21.3)56.7%(46.0-66.0)T790M+15/3716.0m(13.1-NE)72.4%(53.4-84.7)T790M-42/7210.5m(9.2-16.2)49.4%(36.6-61.0)StudyDesignRecruitingSecondaryEndpointsStudyPeriodPrimaryEndpoint12ACCRURC1126(NCT01532089)USA•PhasesIII•Erlotinib+BecvsErlotinib•EGFRMut(+)RecruitingPFSOSORRSafety2012–2017BEVERLY(NCT02633189)Italy2015–2018OSQoLORR•PhasesIII•Erlotinib+BecvsErlotinib•EGFRMut(+)NEJ026(UMIN000017069)Japan2015–2018•PhasesIII•Erlotinib+BecvsErlotinib•EGFRMut(+)ARTEMIS(NCT02759614)China2016–2019•PhasesIII•Erlotinib+BecvsErlotinib•EGFRMut(+)RecruitingRecruitingStatusStudyNo.PFSPFSPFSOSORRSafetyOSQoLORROngoingStudy:erlotinib+bevacizumabvs.erlotinibasfirst-linetreatmentIMPRESS.InexploratoryanalysisofT790Mnegative,theremaybePFSbenefittocontinuationofEGFRTKISoriaJC,etal.LancetOncol.2015;16:990-998.Erlotinib,Gefitinib,Afatinib(8-12m)PD:rebiopsyT790MOsimertinib(8-10m)EGFRdel19L858ROtherInitialbiopsyalso:liquidbiopsyMoketal.,PhaseIII(Aura3)(Osimertinibvs.CT)mPFS10.1vs.4.4mNEJM2016GirardN.Futureoncol2017PlasmaEGFRT790M•PlasmafromAURAtrialsentforBEAMing–Pairedtumorandplasmaavailablefor216patientsOxnardetal,JCO,201618T790M+inplasma,nottumor111T790M+intumorandplasma47T790M+intumor,notplasma40patientsT790M-tumorandplasmaT790M+intumor:62%RR,10mPFST790M+inplasma:63%RR,10mPFSImmunotherapyinEGFR-MutantNSCLC*Dataforthepembrolizumabdoseswerepooled.CheckMate057KEYNOTE-010*OAKNivolumabDocetaxelPembrolizumabDocetaxelAtezolizumabDocetaxelReferencesinslidenotes.Pts,nUnstratifiedHR(95%CI)821.18(0.69-2.00)3400.66(0.51-0.86)1600.74(0.51-1.06)Events/Pts,n/NHR(95%CI)46/860.88(0.45-1.70)447/8750.66(0.55-0.80)Pts,n(%)HR(95%CI)85(10)1.24(0.71-2.18)628(74)0.69(0.57-0.83)MutantNotdetectedNotreportedMutantWildtypeMutantWildtype1.00.52.00.254.01.00.1101.00.22LBA2_PR:OsimertinibvsSoCEGFD-TKIasfirst-linetreatmentinpatientswithEGFRmadvancedNSCLC(FLAURA)•KeyresultsRamalingamSetal.AnnOncol2017;28(suppl5):AbstrLBA2_PRMedianPFS,months(95%CI)18.9(15.2,21.4)10.2(9.6,11.1)HR0.46(95%CI0.37,0.57)p0.0001OsimertinibSoCPFS1.00.60.40.20.003691215182124270.8Probabilityofprogression-freesurvivalTimefromrandomization,monthsNo.atriskOsimertinibSoC27926223321017813907126427723919715210778371020FavoursSoCSubgroupOverall(n=556)LogRank(primary)CoxPHSexMale(n=206)Female(n=350)Ageatscreening65(n=298)≥65(n=258)RaceAsian(n=347)Non-Asian(n=209)SmokinghistoryYes(n=199)No(n=357)CNSmetastasesYes(n=116)No(n=440)WHOperformancestatus0(n=228)1(n=327)EGFRmutationatrandomisation#Exon19deletion(n=349)L858R(n=207)EGFRmutationbyctDNAǂPositive(n=359)Negative(n=124)CentrallyconfirmedEGFRmutation§Positive(n=500)Negative(n=6)¶FLAURAdatacut-off:12June2017Hazardratio1impliesalowerriskofprogressiononosimertinib80mg.Sizeofcircleisproportionaltothenumberofevents*ByInvestigatorassessment;#Localorcentraltest;ǂResultmissingfor36patientsintheosimertinibarmand37patientsintheSoCarm;§Resultmissingfor21patientsintheosimertinibarmand29patientsintheSoCarm;¶Subgroupcategorieswithlessthan20eventswereexcludedfromtheanalysisCNS,centralnervoussystem;ctDNA,circulatingtumourDNA;EGFR,epidermalgrowthfactorreceptor;PFS,progression-freesurvival;SoC,standard-of-care;WHO,WorldHealthOrganization.Ramalingametal.Presentedat:ESMOCongressSep8-12,,2017;Madrid,Spain.PFS*acrosssubgroups0.10.20.30.40.60.8Hazardratio(95%confidenceinterval)0.46(0.37,0.57)0.46(0.37,0.57)0.58(0.41,0.82)0.40(0.30,0.52)0.44(0.33,0.58)0.49(0.35,0.67)0.55(0.42,0.72)0.34(0.23,0.48)0.48(0.34,0.68)0.45(0.34,0.59)0.47(0.30,0.74)0.46(0.36,0.59)0.39(0.27,0.56)0.50(0.38,0.66)0.43(0.32,0.56)0.51(0.36,0.71)0.44(0.34,0.57)0.48(0.28,0.80)0.43(0.34,0.54)NC(NC,NC)2.0PFShazardratioand95%confidenceinterval1.0Favoursosimertinib10.025Objectiveresponserate*FLAURAdatacut-off:12June2017Tickmarksindicatecensoreddata*Byinvestigatorassessment#Analysisperformedusingalogisticregressionstratifiedbyrace(AsianversusNon-Asian)andmutationtype(Exon19deletionversusL858R);ǂResponsedidnotrequireconfirmation;§CalculatedusingKaplan-MeierapproachCI,confidenceinterval;DoR,durationofresponse;ORR,objectiveresponserate;SoC,standard-of-care.Ramalinagmetal.Presentedat:ESMOCongressSep8-12,,2017;Madrid,Spain.DurationofresponseMedianDoR,months(95%CI)17.2(13.8,22.0)8.5(7.3,9.8)Probabilityofremaininginresponse1.00.90.80.70.60.50.40.30.20.10.00369121518212427Timefromfirstresponse(months)No.atriskOsimertinibSoC2232102051801811361609512869823940171440001Osimertinib(n=279)SoC(n=277)ORR(95%CI)80%(75,85)76%(70,81)Oddsratio#(95%CI)1.28(0.85,1.93);p=0.2335Completeresponseǂ,n(%)Partialresponseǂ,n(%)Stabledisease≥6weeks,n(%)Progression,n(%)Notevaluable,n(%)7(3)216(77)47(17)3(1)6(2)4(1)206(74)46(17)14(5)7(3)Estimatedremaininginresponse§,(95%CI)12months18months64%(58,71)49%(41,56)37%(31,44)19%(13,26)OsimertinibSoC26•Keyresults(cont.)RamalingamSetal.AnnOncol2017;28(suppl5):AbstrLBA2_PRNo.atriskOsimertin