CCO-Lung-Fellows-Thatcher-LO-鱗癌培訓(xùn)課件

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ThatcherN,HirschFR,LuftAV,etal.Necitumumabplusgemcitabineandcisplatinversusgemcitabineandcisplatinaloneas

first-linetherapyinpatientswithstageIVsquamousnon-small-celllungcancer〔SQUIRE〕:anopen-label,randomized,controlledphase3trial.LancetOncol.2015;16:763-774.SQUIRE:ImprovedSurvivalWithNecitumumab+Gemcitabine/CisplatinvsGemcitabine/CisplatinasFirst-lineTreatmentinPatientsWithSquamousNSCLCThisactivityissupportedbyeducationalgrantsfromGenentech,Lilly,andNovartisPharmaceuticalsCorporation.AboutTheseSlidesUsersareencouragedtousetheseslidesintheirownnonmercialpresentations,butweaskthatcontent

andattributionnotbechanged.UsersareaskedtohonorthisintentTheseslidesmaynotbepublishedorpostedonline

withoutpermissionfromClinicalCareOptions

〔emailpermission〕Disclaimer

ThematerialspublishedontheClinicalCareOptionsWebsitereflecttheviewsoftheauthorsofthe

CCOmaterial,notthoseofClinicalCareOptions,LLC,theCMEproviders,orthepaniesprovidingeducationalgrants.ThematerialsmaydiscussusesanddosagesfortherapeuticproductsthathavenotbeenapprovedbytheUnitedStatesFoodandDrugAdministration.Aqualifiedhealthcareprofessionalshouldbeconsultedbeforeusinganytherapeuticproductdiscussed.Readersshouldverifyallinformationanddatabeforetreatingpatientsorusinganytherapiesdescribedinthesematerials.Background:NecitumumabinAdvancedSquamousNSCLCPlatinum-baseddoubletchemotherapylongtimestandardfirst-linetreatmentoptionforthe~30%ofptswithsquamousNSCLC[1]Necitumumab:fullyhumanIgG1anti–EGFRmAbAdditiontogemcitabine/cisplatinincreasedantitumoractivityinmousexenograftmodelsofNSCLC[2]FailedtoimproveOSwhenaddedtopemetrexed/cisplatininptswithadvancednonsquamousNSCLCinphaseIIIINSPIREtrial[3]PhaseIIISQUIREtrialevaluatedsafety,efficacyofnecitumumab+gemcitabine/cisplatinvsgemcitabine/cisplatininchemotherapy-naiveptswithstageIVsquamousNSCLC[1]1.ThatcherN,etal.LancetOncol.2015;16:763-774.2.SamakogluS,etal.CancerGenomicProteomics.2012;9:77-92.3.Paz-AresL,etal.LancetOncol.2015;16:328-337.Slidecredit:SQUIRE:PhaseIIIStudySchemaPrimaryendpoint:OS〔ITT〕Secondaryendpoints:PFS,ORR,TTF,safetyThatcherN,etal.LancetOncol.2015;16:763-774.StratifiedbyECOGPS〔0-1vs2〕

andgeographicregion

〔NorthAmerica/Europe/AustraliavsSouthAmerica/SouthAfrica/IndiavseasternAsia〕Chemotherapy-naiveptswithstageIVsquamousNSCLC,ECOGPS0-2,adequateorganfunction〔N=1093〕Slidecredit:Necitumumab800mgIVonDays1,8+Gemcitabine1250mg/m2IVonDays1,8+Cisplatin75mg/m2IVonDay1Q3W(n=545)Gemcitabine1250mg/m2IVonDays1,8+Cisplatin75mg/m2IVonDay1Q3W(n=548)Maximum6cyclesPtswithoutPDreceivingnecitumumabcouldcontinueonsingle-agentnecitumumabuntilPDorunacceptabletoxicityPDOSsignificantlyimprovedwithnecitumumab+gemcitabine/cisplatinvsgemcitabine/cisplatinaloneSQUIRE:OSThatcherN,etal.LancetOncol.2015;16:763-774.Slidecredit:0204060801000246810121416182022242628303234363840MosOS(%)N+G/CCensoredptsG/CCensoredptsN+G/C(n=545)

G/C(n=548)HR:0.84(95%CI:0.74-0.96;P=.01)MedianOS,

Mos(95%CI)

11.5(10.4-12.6)

9.9(8.9-11.1)1-YrOS,

%(95%CI)

48(43-52)43(39-47)2-YrOS,

%(95%CI)

20(16-24)17(13-20)SQUIRE:OSbySubgroupSlidecredit:0.451.51Favorsnecitumumabplusgem/cisplatinFavorsgem/cisplatinThatcherN,etal.LancetOncol.2015;16:763-774.SQUIRE:PFSPFSsignificantlyimprovedwithnecitumumab+gemcitabine/cisplatinvsgemcitabine/cisplatinaloneMedianTTF:4.3vs3.6mos,respectively〔P=.006〕ThatcherN,etal.LancetOncol.2015;16:763-774.Slidecredit:HR:0.85〔95%CI:0.74-0.98;

P=.02〕MedianPFS,

Mos〔95%CI〕

5.7〔5.6-6.0〕5.5〔4.8-5.6〕3-MoPFS,

%〔95%CI〕

79〔76-83〕73〔68-76〕6-MoPFS,

%〔95%CI〕

45〔40-49〕37〔33-42〕N+G/C〔n=545〕

G/C〔n=548〕0204060801000246810121416182022242628303234MosPFS(%)N+G/CCensoredptsG/CCensoredptsSQUIRE:ResponsesORRsimilarbetween2groups,butdiseasecontrolwasmoremonwiththeadditionofnecitumumab〔P=.043〕Slidecredit:ThatcherN,etal.LancetOncol.2015;16:763-774.Response,%Necitumumab+Gemcitabine/Cisplatin〔n=545〕Gemcitabine/Cisplatin〔n=548〕ORR,%〔95%CI〕CRPR31〔27-35〕03129〔25-33〕<128SD5148PD810DCR,%〔95%CI〕82〔78-85〕77〔73-80〕Notevaluable<12Notassessed1011SQUIRE:EfficacybyEGFRExpressionEGFRexpressionnotpredictiveorprognosticofsurvivalbenefitTrendtowardimprovedOSwithhighEGFRexpressionSlidecredit:ThatcherN,etal.LancetOncol.2015;16:763-774.Oute,HR〔95%CI〕HighEGFRExpression*〔n=374〕LowEGFRExpression*〔n=608〕InteractionPValueOS0.75〔0.60-0.94〕0.90〔0.75-1.07〕.24PFS0.88〔0.70-1.11〕0.83〔0.69-0.99〕.68ORR0.97〔0.62-1.50〕1.27〔0.90-1.79〕.34*EGFRexpressiondeterminedin982ptswithevaluablesamplesviaIHCassaywithEGFRPharmDxKit〔Dako〕andindependentlyscoredby2pathologists.High:H-score≥200;low:H-score<200.Treatment-RelatedAEsofInterest,%Necitumumab+Gemcitabine/Cisplatin〔n=538〕Gemcitabine/Cisplatin〔n=541〕AnyGradeGrade≥3AnyGradeGrade≥3Any99729862SkinreactionsRash7976871210<1<1NeutropeniaFebrileneutropenia44124<1462281Fatigue437437Anemia42114611Hypomagnesemia319161Thrombocytopenia22102711Diarrhea162112Venousthromboembolicevents9553Conjunctivitis7<120Arterialthromboembolicevents5442Hypersensitivity/infusionrxn1<120InterstitialLungdisease1<1<1<1SQUIRE:MostmonAEsSlidecredit:ThatcherN,etal.LancetOncol.2015;16:763-774.ConclusionsandFacultyAssessmentNecitumumabadditiontogemcitabine/cisplatinconferredsignificantsurvivalbenefittochemotherapy-naiveptswith

stageIVsquamousNSCLCvsgemcitabine/cisplatinaloneMedianOS:11.5vs9.9mos〔P=.01〕MedianPFS:5.7vs5.5mos〔P=.02〕Grade≥3andseriousAEsmoremonwithnecitumumab+gemcitabine/cisplatinvsgemcitabine/cisplatin〔72%vs62%and48%vs38%,respectively〕Necitumumabplusgemcitabine/cisplatinapprovedbyFDAforfirstlinetreatmentofpatientswithmetastaticsquamousNSCLCSlidecredit:ThatcherN,etal.LancetOncol.2015;16:763-774.ConclusionsandFacultyAssessmentEGFR