肺癌免疫治疗进展专家讲座

肺癌免疫治疗进展肺癌免疫治疗进展第1页FutureOutlookUpdateofcheckpointInhibitorsinlungcancertherapyCancerImmunotherapy123Outline肺癌免疫治疗进展第2页FutureOutlookUpdateofcheckpointInhibitorsinlungcancertherapyCancerImmunotherapy123Outline肺癌免疫治疗进展第3页

肿瘤免疫治疗—攻克肿瘤新希望

人类抗击肿瘤历史肿瘤免疫治疗含有特异性和靶向性，一直为临床医师高度关注，近年进步显著，使得免疫治疗成为更具期待领域1896年coley毒素应用于临床1899年放疗治愈第1例病人1946年氮芥治疗淋巴瘤获得成功免疫治疗放疗化疗靶向治疗进入21世纪，分子靶向治疗如火如荼肺癌免疫治疗进展第4页eKeyeventsinthehistoryofcancerimmunotherapy1890s1stCAvaccinedeveloped(coley)1973discoveryofthedendriticcell(steinman)19761ststudywithBCGinbladderCA1978DiscoveryoftumorspecificmABs19851ststudywithadoptiveT-celltransferinCA1986IFNα(cytokine)approvedforCA1990sDiscoveryofroleofcheckpointsinCA1992Il-2(Cytokine)approvedforCA19971stmABapprovedforCA1stcellularimmunotherapyapprovedforCA1stcheckpointinhibitorapprovedforCA2ndcheckpointinhibitorapprovedforCAEnthusiasmphase1976-1985Skepticismphase1986-1992Renaissancephase1997-肺癌免疫治疗进展第5页美国《Science》杂志:年六大值得关注科学领域单细胞测序“普朗克”探测微波背景辐射人类连接组计划探索南极冰下世界癌症免疫疗法基础植物研究肺癌免疫治疗进展第6页Breakthroughofyear

Science.Dec20;342(6165):1432-3肺癌免疫治疗进展第7页Immunity.39(1)25July,Pages1–10StimulatoryandInhibitoryFactorsintheCancer-ImmunityCycle肺癌免疫治疗进展第8页CTLA-4andPD-1/PD-L1checkpoint

blockadeforcancertreatment肺癌免疫治疗进展第9页CTLA-4andPD-1/PD-L1

CheckpointBlockadeforCancerTreatmentImmunecheckpointblockadeincludesagentstargetingthenegativeregulatorsCTLA-4andPD-1CTLA-4attenuatestheearlyactivationofnaiveandmemoryTcellsinthelymphnodes

AgentstargetingCTLA-4includeipilimumabandtremelimumabIncontrast,PD-1modulatestheeffectorphaseofTcellactivityinperipheraltissuesviainteractionwithPD-L1andPD-L2AgentstargetingPD-1includenivolumabandMK-3475

AgentstargetingPD-L1includeMPDL3280AandMEDI4736KyiC,etal.FEBSLett.;588:368-376肺癌免疫治疗进展第10页ComparingCTLA-4andPD-1CTLA-4PD-1BiologicalfunctionInhibitoryreceptorInhibitoryreceptorExpressiononTcellsatthetimeofinitialresponsetoantigen(activatedCD8+Tcells)ActivatedTcells,Bcells,NKcellsTILsindifferenttumortypesMajorroleRegulatestheearlystageofT-cellactivationLimitsT-cellactivityinperipheraltissueafterinflammatoryresponseLimitsautoimmunityLigandsB7.1(CD80)B7.2(CD86)PD-L1(B7-H1/CD274)PD-L2(B7-CD/CD273)MechanismofactionAfterligandbinding:BindingwithPI3K,phosphatasesSHP-2andPP2ABlockadeoflipid-raftexpressionBlockadeofmicroclusterformationAfterligandbinding:Recruitsinhibitoryphosphatase,SHP-2DecreasesexpressionofcellsurvivalproteinBcl-xLInhibitskinases(PI3K/AKT)involvedinT-cellactivationCritRevOncolHematol.;89:140-165.CTLA-4andPD-1haveseparatebutcomplimentaryrolesinimmuneresponses肺癌免疫治疗进展第11页FutureOutlookUpdateofcheckpointInhibitorsinlungcancertherapyCancerImmunotherapy123Outline肺癌免疫治疗进展第12页CTLA-4CheckpointInhibitor肺癌免疫治疗进展第13页Anti-CTLA-4antibodiescaninduce

clinicalresponseinabroadvarietyofcancerAdaptedformLebbeetal.ESMOPresentedByLawrenceFongatASCOAnnualMeetingBladderRenalEsophagealCNSColorectalGlioblastomaLeukemiaSoftTissueSarcoma肺癌免疫治疗进展第14页JClinOncol.Jun10;30(17):2046-54AnnOncol.Jan;24(1):75-83肺癌免疫治疗进展第15页JClinOncol.Jun10;30(17):2046-54IpilimumabincombinationwithPCasfirst-linetherapyinstageIIIB/IVNSCLC肺癌免疫治疗进展第16页Kaplan–MeierplotsforOSJClinOncol.Jun10;30(17):2046-54Deaths/patients51/6651/68Median(95%CI),months8.28(6.80to12.39)12.22(9.26to14.39)HR(95%CI)

0.87

(0.59

to

1.28)Log-rankP0.23ControlPhasedIpiDeaths/patients51/6651/70Median(95%CI),months8.28(6.80to12.39)9.69(7.59to12.48)HR(95%CI)

0.99(0.67to1.46)Log-rankP0.48ConcurrentlpiControl肺癌免疫治疗进展第17页Events/patients61/6658/70Median(95%CI),mo4.21(2.76to5.32)4.11(2.76to5.32)HR(95%CI)

0.88(0.61to1.27)Log-rankP.25JClinOncol.Jun10;30(17):2046-54Kaplan–MeierplotsforPFSperimmune-related(ir)responsecriteria(irPFS)andmodifiedWHOcriteria(mWHO-PFS).Events/patients56/6654/68Median(95%CI),4.63m(4.14to5.52)5.68(4.76to7.79)HR(95%CI)

0.72

(0.50to1.06)Log-rankP.05ControlPhasedIpiEvents/patients56/6655/70Median(95%CI),4.63m(4.14to5.52)5.52(4.17to6.74)HR(95%CI)

0.81(0.55to1.17)Log-rankP.13ControlConcurrentlpiEvents/patients61/6656/68Median(95%CI),mo4.21(2.76to5.32)5.13(4.17to5.72)HR(95%CI)

0.69(0.48to1.00)Log-rankP.02ControlPhasedIpiControlConcurrentlpi肺癌免疫治疗进展第18页AdverseEventsJClinOncol.Jun10;30(17):2046-54肺癌免疫治疗进展第19页Follow-UPEvery12wksForsurvivalSCREENINGINDUCTIONMAINTENANCEFOLLOW-UPCA184-104:phaseIIItrialcomparingthetheefficacyofipilimumab(Ipi)withPCversusplacebowithPCinpatients(pts)withstageIV/recurrentNSCLCofsquamoushistologyTumorassessmentEvery12wksIpi10mg/kg+PCWks7,10,13,16stageIV/recurrentsquamousNSCLCECOG≤1Placebo+PCWks7,10,13,162cyclePC

Wks1,

4Ipi10mg/kgEvery12wksPlaceboEvery12wksRJClinOncol31,(suppl;abstrTPS8117)primaryendpointOSsecondaryendpointsOSamongptswhoreceiveblindedtherapyPFSbestoverallresponserateTumorassessmentWks7,13,19,25ExclusionCriteria:BrainMetastasesAutoimmunediseasesPCPaclitaxel(175mg/m2,

IV)+Carboplatin(AUC=6,

IV)肺癌免疫治疗进展第20页CA184-156:PhaseIIITrialComparingtheEfficacyofIpiPlusEtoposide/PlatinumVersusEtoposide/PlatinuminSubjectsWithNewlyDiagnosedED-SCLCJClinOncol30,(suppl;abstrTPS7113)Ipi+EPQ3W2cycleED-SCLCECOG0-1Placebo+EPQ3W2cycleSCREENINGINDUCTIONMAINTENANCE2cycleEP

Ipi10mg/kgQ12WPlaceboQ12WRprimaryendpointOSsecondaryendpointsOSamongptswhoreceiveblindedtherapyimmune-relatedandmWHOPFSbestoverallresponseratedurationofresponseExclusionCriteria:PriorsystemictherapyforlungcancerSymptomaticCNSmetastasesHistoryofautoimmunediseaseIpiQ3W2cycleEP：etoposide(100mg/m^2,IVonDays1-3Q3W)+cisplatin(75mg/m^2,IV)or+carboplatin(AUC=5,IV)onceQ3WIpi:(10mg/kg,IV,Q3W)PlaceboQ3W2cycle肺癌免疫治疗进展第21页APhaseIIIStudyofNivolumabinCombinationwithYervoyinPatientswithAdvancedNon-SmallCellLungCancer肺癌免疫治疗进展第22页PD-1/PD-L1CheckpointInhibitors肺癌免疫治疗进展第23页PD-1andPD-L1antibodiesinphaseIIIdevelopment肺癌免疫治疗进展第24页Phase1Nivolumab(anti-PD-1;BMS-936558,ONO-4538)multidoseregimenEligibility:advcancedmelanoma,NSCLC,RCC,CRC,orCRPCwithPDafter1-5systemictherapies肺癌免疫治疗进展第25页SelectAes(>1%)occuringinPtswithNSCLCtreatedwithNivolumab(N=129)Drug-relatedpneumonitis(anygrade)occurredin8NSCLCPts(6%)VS12Pts(4%)intheoverallstudypopulation-3Pts(2%)withNSCLChadgrade¾pneumonitis肺癌免疫治疗进展第26页EfficacyofNivolumabmonotherapy

inPtstreatedwithNSCLC肺癌免疫治疗进展第27页NivolumabincombinationwithPT-DCinadvancedNSCLCAntoniaSJ,etal.ASCOAbstract8113.肺癌免疫治疗进展第28页ResultsandConclusions治疗前6周没有发生剂量限制毒性3-4级治疗相关不良事件发生率为45%ORR：33-50%1年OS：59-87%Nivo10+gem/cis鳞癌Nivo10+pem/cis非鳞癌Nivo10+pac/carb鳞+非鳞癌Nivo5+pac/carb鳞+非鳞癌N12151514ORR,n(%)4(33)7(47)7(47)7(50)mDOR(范围)，周20.9(12.1-41.7)32.0(13,1-42.1)25.6(11.4-39.0)NA(11.4-37.3)PD为BOR,n(%)003(20)1(7)24周时PFS,%367138571年OS,%598759NAAntoniaSJ,etal.ASCOAbstract8113.AntoniaSJ,etal.ASCOAbstract8113.肺癌免疫治疗进展第29页OngoingNivolumabClinical

TrialsinPatientsWithNSCLCLineoftherapyPhasePD-L1SelectionComparatorSingleagentNivolumab1stline[1]IIIYesChemotherapy2ndline,squamous[2]IIINoDocetaxel2ndline,adeno[3]IIIYesDocetaxel≥2ndline,squamous[4]IINoNACombinationNivolumab≥2ndline[5]INo+LAG3≥2ndline[6]INo+lirilumab(KIR)1stline[7]INoSingleagent;+chemotherapy;+bevacizumab;+erlotinib;+ipilimumabClinicalT.NCT02041533.2.ClinicalT.NCT0164.3.ClinicalT.NCT01673867.4.ClinicalT.NCT01721759.5.ClinicalT.NCT01968109.6.ClinicalT.NCT01714739.7.ClinicalT.NCT01454102.肺癌免疫治疗进展第30页PartsCtoF:AdditionalMELandNSCLCcohortsMK3475(Pembrolizumab,Anti-PD-1):

PhaseITrialDesignAprNovDecJanFebMarAprMayJunJulAugSepOctNovDecIPI-N10q2w

(n=41)IPI-N10q3w

(n=24)PartA:DoseEscalationIPI-N2q3w

(n=22)IPI-T10q2w

(n=16)IPI-T10q3w

(n=32)PartB:Metastaticorlocallyadvanced,unresectableMELRibasAetal.ASCO.Abstract9009.肺癌免疫治疗进展第31页KEYNOTE-001：

NSCLC扩大队列研究设计(N=307)非随机(N=33)PD-L1+2次治疗非随机(N=40)PD-L1+2次治疗最少1次含铂随机(N=144)PD-L1+1次治疗最少1次含铂随机(N=45)PD-L1+初治非随机(N=45)PD-L1+1次治疗最少1次含铂Pembro10mg/kgq3wPembro10mg/kgq2wPembro10mg/kgq3wPembro10mg/kgq2wPembro10mg/kgq2wPembro10mg/kgq3wPembro2mg/kgq3wPembro2mg/kgq3wR(3:2)R*(1:1:1)*前11例患者随机分入2mg/kgq3w和10mg/kgq3w组，剩下34例患者随机接收10mg/kgq2w和10mg/kgq3w组****非随机队列45例接收2mg/kgq3w患者分析截止日期为年9月11日数据截止日期：年3月3日GaronEB,etal.ESMOAbstractLBA43.主要终点：ORR(RECISTv1.1[独立中心评定])次要终点：免疫相关疗效标准(irRC)[研究者评定]Pembrolizumab(MK3475)治疗连续直至PD，不可接收毒性或死亡肺癌免疫治疗进展第32页KEYNOTE-001：基线特征特征

N=262年纪，中位(范围)，岁65(28-86)男性50%ECOGPS：0/1/缺失31%/68%/1%人种：白种/黑人或非裔美国人/亚裔/其它83%/4%/11%/2%鳞癌17%既往接收治疗次数：0/>=117%/83%分期：M0/M1a/M1b/未知13%/28%/49%/11%脑转移瘤史5%EGFR突变(N=250)16%KRAS突变(N=156)26%ALK基因重排(N=231)3%吸烟史：当前/曾经/从不/未知5%/64%/28%/2%GaronEB,etal.ESMOAbstractLBA43.肺癌免疫治疗进展第33页KEYNOTE-001：

治疗暴露与治疗相关不良事件汇总4例患者(1.5%)发生输注相关反应发生率<1%其它潜在免疫调整不良事件为结肠炎和低钠血症治疗暴露N=262中位(范围)治疗时间(d)85.5(1-400)中位(范围)剂量(n)5.5(1-23)治疗相关不良事件总结(%)任何级别67%3-4级9%死亡0.4%终止3%不良事件发生率N=262任何级别3-5级治疗相关不良事件(发生率≥5%)乏力20%<1%瘙痒9%0关节痛8%<1%食欲减退8%0腹泻7%0甲状腺功效减退6%0发烧6%0皮疹6%0恶心5%<1%其它关注临床不良事件(发生率≥1%)肺炎4%2%甲状腺功效亢进2%<1%GaronEB,etal.ESMOAbstractLBA43.肺癌免疫治疗进展第34页KEYNOTE-001：

肿瘤大小自基线最大改变*(%)

(RECISTv1.1，中心评定)*可评定患者为依据中心评定基线有可测量病灶且最少接收一次基线后肿瘤评定GaronEB,etal.ESMOAbstractLBA43.肺癌免疫治疗进展第35页KEYNOTE-001：抗肿瘤活性

(RECISTv1.1，中心评定)a包含确认和未确认缓解；b数据截止日期为年3月3日GaronEB,etal.ESMOAbstractLBA43.

NORR%(95%CI)总计23621(16-27)治疗史236未经治疗4226(14-42)曾接收过治疗19420(15-26)组织学230非鳞癌19123(17-29)鳞癌3918(8-34)吸烟史230当前/曾经16527(20-34)从不659(4-19)

NORR%(95%CI)给药方案2362Q3W633(4-78)10Q3W12621(14-29)10Q2W10421(14-30)PD-L1表示236阳性20123(18-30)阴性359(2-23)EGFR突变3614(5-30)KRAS突变3928(15-45)ALK基因重排617(0-64)肺癌免疫治疗进展第36页KEYNOTE-001：

抗肿瘤活性(irRC，研究者评定)a包含确认和未确认缓解；b数据截止日期为年9月11日GaronEB,etal.ESMOAbstractLBA43.额外45例接收2mg/kgq3w治疗患者中，ORRa为20%(95%CI:10%-35%)bNORR%(95%CI)总计26223(18-29)治疗史262未经治疗4547(32-62)曾接收过治疗21718(13-24)组织学258非鳞癌21223(17-29)鳞癌4425(13-40)吸烟史256当前/曾经18227(21-34)从不7414(7-24)NORR%(95%CI)给药方案2622Q3W667(22-96)10Q3W14122(16-30)10Q2W11522(15-30)PD-L1表示262阳性22225(19-31)阴性4013(4-27)EGRFR突变4112(4-26)KRAS突变4132(18-48)ALK重排633(4-78)肺癌免疫治疗进展第37页KEYNOTE-001：

至缓解时间&缓解连续时间a包含确认和未确认缓解GaronEB,etal.ESMOAbstractLBA43.肺癌免疫治疗进展第38页KEYNOTE-001：

生存期评定：初治vs.复治GaronEB,etal.ESMOAbstractLBA43.初治复治中位PFS(周)271024周PFS(%)5126初治复治中位OS(月)NR8.26个月OS(%)8659肺癌免疫治疗进展第39页KEYNOTE-001：

生存期评定：不一样剂量GaronEB,etal.ESMOAbstractLBA43.全组人群中位PFS(周)13.024周PFS(%)30全组人群中位OS(月)8.26个月OS(%)64肺癌免疫治疗进展第40页KEYNOTE-001：

PD-L1表示水平与缓解率GaronEB,etal.ESMOAbstractLBA43.肺癌免疫治疗进展第41页KEYNOTE-001：

生存期评定：PD-L1表示PD-L1强阳性：>=50%肿瘤细胞PD-L1弱阳性：1-49%肿瘤细胞染色阴性为PD-L1无表示GaronEB,etal.ESMOAbstractLBA43.PD-L1强阳性患者较弱阳性/阴性患者PFS更长(HR=0.52;95%CI:0.33-0.80)PD-L1强阳性患者较弱阳性/阴性患者OS更长(HR=0.59;95%CI:0.35-0.99)肺癌免疫治疗进展第42页KEYNOTE-001：

总结与结论在初治(ORR26%)和复治(ORR20%)晚期NSCLC患者中，全部剂量和方案都观察到很好抗肿瘤活性2mg/kgq3w剂量下，ORR为20%(irRC)缓解持久安全性及毒性可管理PD-L1强表示与缓解率(37%)、PFS(HR=0.52)、OS(HR=0.59)改进相关在KEYNOTE-001研究额外入组300例患者中将前瞻性验证PD-L1截点GaronEB,etal.ESMOAbstractLBA43.肺癌免疫治疗进展第43页4/49PD-L1IdentifiesPtsWithNSCLCMostLikelytoBenefitFromMK-3475(Pembrolizumab,Anti-PD-1)StrongPD-L1positivestainingwasconsidered≥50%oftumorcells,andweakwasdefinedasstainingbetween1%to49%ofpositivelystainingtumorcells.NegativehadnotumorstainingforPD-L1.ResponseRate(%)3/427/4615/4125/129GandhiL,etal.AACR.AbstractCT105.Reprintedwithpermission.RR-RECIST1.1504030201001937157Total1%-49%PD-L1staining≥50%PD-L1stainingPD-L1negativeResponseRate(%)4/5320/4428/146RR-irRC50403020100194688n/N:n/N:肺癌免疫治疗进展第44页OngoingMK-3475(Pembrolizumab,Anti-PD-1)

ClinicalTrialsinPatientsWithNSCLCLineofTherapyPhasePD-L1SelectionComparatorSingle-agentMK-34751stline;≥2ndline[1,2]I/IIBothNA2ndline[3]IIIYesDocetaxel1stline[4]IIIYesChemotherapyCombinationMK-3475NA[5]I/IINoSingleagent;+chemotherapy;+pemetrexed;+gefitinib;+erlotinib;+ipilimumab1.ClinicalT.NCT02085070.2.ClinicalT.NCT02129556.3.ClinicalT.NCT01905657.4.ClinicalT.NCT02142738.5.ClinicalT.NCT02039674.肺癌免疫治疗进展第45页ExamplesofPD-L1NSCLC

SampleIHCStaining*PD-L1NegativePD-L1Positive*Clinicaltrialassay.StainingIntensity0+1+2+3+PD-L1Positivity,%02100100GandhiL,etal.AACR.AbstractCT105.Reprintedwithpermission.肺癌免疫治疗进展第46页PhaseIStudyofMPDL3280A

(Anti-PDL-1)inNSCLCMPDL3280A:anti–PD-L1antibodyengineeredforenhancedsafetyandefficacyPatientswithmetastaticsolidtumorsEGFRandKRASstatusassessedatbaselineStudydesign:MPDL3280AIVevery3wksx16cycles(≈1yr)Primaryendpoint:safetySecondaryendpoint:ORRbyRECISTv1.1BaselinedemographicsCharacteristicsn=85*Medianage,yrs(range)60(24-84)Sex,male/female,n(%)48(56)/37(44)ECOGPS,0/1,n(%)27(32)/58(68)Histology,n(%)Squamous20(24)Nonsquamous65(76)*Safetyevaluablepatients(n=85)withNSCLC.DatacutoffApril30,.†Systemicregimensadministeredinthemetastatic,adjuvantorneoadjuvantsetting.3%ofpatientshadnoprevioussystemicregimens.Characteristics,n(%)n=85*Previoussystemicregimens†1or236(42)≥347(55)SmokingstatusCurrent/previous68(80)Never17(20)HornL,etal.WCLC.AbstractMO18.Reprintedwithpermission.肺癌免疫治疗进展第47页PD-L1Status*(N=53)ORR,†%(n/N)PtsWithPD,%(n/N)

IHC3(n=6)83(5/6)17(1/6)IHC2and3(n=13)46(6/13)23(3/13)IHC1/2/3(n=26)31(8/26)38(10/26)Allpatients(IHC0/1/2/3and7patientswithdiagnosticunknown;

N=53)23

(12/53)40

(21/53)DurationofTreatmentandResponseWkHistologyIHCNSIHC0SIHC3NSIHC0NSIHC1NSIHC0SIHC2NSIHC3SIHC3NSIHC3NSIHC0NSIHC3NSIHC1*PD-LIstatusdeterminedusingproprietaryGenentechRocheIHC.†ORRincludesinvestigator-assessedunconfirmedandconfirmed(u/c)PRperRECIST1.1.Patientsfirstdosedat1-20mg/kgbyOctober1,.DatacutoffApril30,.MPDL3280A(Anti-PDL-1)inNSCLC:BestResponsebyPD-L1StatusandDOT/DORHornL,etal.WCLC.AbstractMO18.Reprintedwithpermission.0612182430364248546066727884Onstudy,ontreatment

Onstudy,posttreatment

Treatmentdiscontinued

Ongoingresponse

FirstresponseFirstPD肺癌免疫治疗进展第48页*ORRincludesinvestigator-assessedu/cPRbyRECIST1.1.Patientsfirstdosedat1-20mg/kgbyOctober1,.DatacutoffApril30,.Former/

CurrentSmokersNever

SmokersResponsebySmokingStatus(ORR*)SmokingStatus(NSCLC;n=53)PtsWithPR(%)EGFRMutantEGFRStatus(NSCLC;n=53)UnknownResponsebyEGFRStatus(ORR*)PtsWithPR(%)KRASStatus(NSCLC;n=53)ResponsebyKRASStatus(ORR*)PtsWithPR(%)KRASMutantUnknownEGFRWTEGFRMutantKRASWTKRASMutant11/431/109/401/68/271/10MPDL3280A(Anti-PDL-1)PhaseIa:

ResponsebySmokingandMutationalStatusHornL,etal.WCLC.AbstractMO18.Reprintedwithpermission.504030201005040302010050403020100Former/CurrentSmokersNeverSmokers26%10%23%17%30%10%51%30%19%76%13%11%81%19%KRASWTEGFRWT肺癌免疫治疗进展第49页MajorityofAEsweregrade1/2anddidnotrequireinterventionNoMTDordose-limitingtoxicitiesNograde3-5pneumonitisobservedTreatment-relateddeath(cardio-respiratoryarrest)in1patientwithsinusthrombosisandlargetumormassinvadingtheheartatbaselineImmune-relatedgrade3.4AEs:1patientwithlarge-cellneuroendocrineNSCLC(diabetesmellitus,1%)MPDL3280A(Anti-PDL-1):Treatment-RelatedAdverseEventsinPatientsWithNSCLC*AEsoccurringin≥5%ofpatients.†Grade3/4treatment-relatedAEslistedincludetreatment-relatedAEsforwhichtheanygradeoccurrencewas≥5%ofpatients.DatacutoffApril30,.AdverseEvent(n=85)TreatmentRelated,%(n)AnyGrade*Grade3/4†AnyAE66(56)11(9)Fatigue20(17)2(2)Nausea14(12)1(1)Decreasedappetite12(10)0Dyspnea9(8)1(1)Diarrhea8(7)0Asthenia7(6)0Headache7(6)0Rash7(6)0Pyrexia6(5)0Vomiting6(5)1(1)Upperrespiratorytractinfection5(4)0HornL,etal.WCLC.AbstractMO18.Reprintedwithpermission.肺癌免疫治疗进展第50页OngoingMPDL3280A(Anti-PDL-1)

ClinicalTrialsinPatientsWithNSCLCLineofTherapyPhasePD-L1SelectionComparatorSingle-agentMPDL3280A1stline;≥2ndline[1]IIYesNA1stline;≥2ndline[2]IIYesNA2ndline[3]IINoDocetaxel≥2ndline[4]IIINoChemotherapyCombinationMPDL3280AExpansion:EGFRm