肺癌免疫治疗进展FutureOutlookFutureOutlook肿瘤免疫治疗—攻克肿瘤的新希望美国《Science》杂志:2013年六大值得关注的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Breakthroughofyear2013Immunity.39(1)25July2013,Pages1–10CTLA-4andPD-1/PD-L1checkpointblockadeforcancertreatmentCTLA-4andPD-1/PD-L1CheckpointBlockadeforCancerTreatmentComparingCTLA-4andPD-1FutureOutlookCTLA-4CheckpointInhibitorAnti-CTLA-4antibodiescaninduceclinicalresponseinabroadvarietyofcancerJClinOncol.2012Jun10;30(17):2046-54Kaplan–MeierplotsforOSEvents/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.25AdverseEventsFollow-UPEvery12wksForsurvivalCA184-156:PhaseIIITrialComparingtheEfficacyofIpiPlusEtoposide/PlatinumVersusEtoposide/PlatinuminSubjectsWithNewlyDiagnosedED-SCLCAPhaseIIIStudyofNivolumabinCombinationwithYervoyinPatientswithAdvancedNon-SmallCellLungCancerPD-1/PD-L1CheckpointInhibitorsPD-1andPD-L1antibodiesinphaseIIIdevelopmentPhase1Nivolumab(anti-PD-1;BMS-936558,ONO-4538)multidoseregimenSelectAes(>1%)occuringinPtswithNSCLCtreatedwithNivolumab(N=129)EfficacyofNivolumabmonotherapyinPtstreatedwithNSCLCNivolumabincombinationwithPT-DCinadvancedNSCLCResultsandConclusionsOngoingNivolumabClinicalTrialsinPatientsWithNSCLCPartsCtoF:AdditionalMELandNSCLCcohortsKEYNOTE-001：NSCLC扩大队列研究设计(N=307)KEYNOTE-001：基线特征KEYNOTE-001：治疗暴露与治疗相关不良事件汇总KEYNOTE-001：肿瘤大小自基线最大变化*(%)(RECISTv1.1，中心评估)KEYNOTE-001：抗肿瘤活性(RECISTv1.1，中心评估)KEYNOTE-001：抗肿瘤活性(irRC，研究者评估)KEYNOTE-001：至缓解时间&缓解持续时间KEYNOTE-001：生存期评估：初治vs.复治KEYNOTE-001：生存期评估：不同剂量KEYNOTE-001：PD-L1表达水平与缓解率KEYNOTE-001：生存期评估：PD-L1表达KEYNOTE-001：总结与结论OngoingMK-3475(Pembrolizumab,Anti-PD-1)ClinicalTrialsinPatientsWithNSCLCPhaseIStudyofMPDL3280A(Anti-PDL-1)inNSCLCPD-L1Status*(N=53)*ORRincludesinvestigator-assessedu/cPRbyRECIST1.1.Patientsfirstdosedat1-20mg/kgbyOctober1,2012.DatacutoffApril30,2013.MajorityofAEsweregrade1/2anddidnotrequireinterventionNoMTDordose-limitingtoxicitiesNograde3-5pneumonitisobservedTreatment-relateddeath(cardio-respiratory