2023免疫檢查點抑制劑提高實體瘤治愈率

2023免疫檢查點抑制劑提高實體瘤治愈率有些影響因子較低又是國人常發(fā)的一些水刊存在的意義之一就是方便我梳理國內(nèi)一些研究進度。昨天的文章聚焦的是圍術(shù)期免疫為基礎(chǔ)的聯(lián)合治療方案失利的消息。原本就是極速推進的免疫治療，必然在校正。這是既往手術(shù)、放療、化療、靶向治療賽道都經(jīng)歷過的審慎到狂熱再恢復(fù)理智的三個階段。免疫治療已成為癌癥治療的核心支柱。免疫檢查點抑制劑(ICIs)是腫瘤免疫療法的一個主要類別，可以重新激活先前存在的抗腫瘤免疫。最初，IQ僅被批準(zhǔn)用于化療后或化療同時進行的挽救治療階段的晚期和轉(zhuǎn)移性腫瘤患者，整體有效率大約為20-30%。隨著十年來的重大進展，ICIs作為可切除實體瘤的新輔助和/或輔助療法的臨床試驗正逐步增多。這些試驗取得了可喜的結(jié)果，F(xiàn)DA批準(zhǔn)ICIs作為非小細胞肺癌、黑色素瘤、三陰性乳腺癌癥和膀胱癌癥的新輔助或輔助治療藥物，該名單還在繼續(xù)增加。這種治療模式意味著癌癥治療的范式轉(zhuǎn)變，因為許多早期腫瘤患者可以通過早期引入免疫治療來獲得治愈的可能。這篇綜述文章總結(jié)了基于ICI的免疫療法的現(xiàn)狀，強調(diào)了IQs作為早期腫瘤新輔助和輔助治療的臨床發(fā)展前景。Fig.1FDAapprovalsoffifst-lineimmunotherapyforadvanced/metastatccancer圖1.FDA批準(zhǔn)的用于晚期/轉(zhuǎn)移性腫瘤患者一線免疫治療方案Neoadjuvant Activatedimmunecellskilltumor,Immunotherapycel,sandshrinktumorst0Militate、 resectionandpreventrecurrence.E星除14翻SurgicallyremovalAdjuvantImmunotherapyAntibodiesSurgicallyremovaltumorsActivatedimmunecellskillmoretumorcellsatthe

tumorbedanderadicatemicrometastasisFig.2NeoadjuvantvsAdjuvantImmunotherapyinsolidtumors圖2.實體瘤領(lǐng)域新輔助vs輔助免疫治療Fig.3FDAapprovalsofneoadjuvantandadjuvantimmunotherapyforlocalizedcancer圖3.FDA批準(zhǔn)的新輔助和輔助免疫治療研究NCTOS27O824AdvanceGastricAdenocarciIII120Radicalsurgeryafterneoadjuvant2027nomaimmunotherapy(albuminPacliraxel+SeggK>+PD-1inhibitor)VSadicalsurgeryafterneoad*juvantchemotherapy(albuminPachtaxel+Seggio)NCT04882241GastrkCancerNCTOS27O824AdvanceGastricAdenocarciIII120Radicalsurgeryafterneoadjuvant2027nomaimmunotherapy(albuminPacliraxel+SeggK>+PD-1inhibitor)VSadicalsurgeryafterneoad*juvantchemotherapy(albuminPachtaxel+Seggio)NCT04882241GastrkCancerIII120Pembrolizumab(MK-3475)PlusChemotherapy(XPorFP)VSPldccboPlusChemotherapy(XPorFP)asNeoadjuvant/AdjuvantTreatment2025GUNCT03732677MuscleInvasiveBladderCancerIII988DurvdlumabinCombinationWithGemcitabine-4-CisplatinfoeNeoodjuvanxTreatmentFollowedbyDurvalumabAlone2026NCT04700124MuscleInvasiveBladderCancerIII784PecioperauveEnfortumabVedotinPlusPembrolizumab2026(MK-3475)VSNeoadjuvantGemcitabineandCisplatinNCT04209114Muscle-InvasiveBladderCancerIII540NeoadjuvantandAdjuvant2024(MI8C)WhoAreCisplatinNivolumabPlusNKTR-214,VSIneligibleNivolumabAloneVersusStandardofCareNCT04209114MI8CineligibleforcisplatinIII540NeoadjuvantandAdjuvantNivolumab-4-Bempeg/NKTR-214,VSNivolumabAlone2024vsStandardofCarewradicalcystectomyNCTO47OO124(KEYNOTE-815)CispUtirveligibleMuscleInvaIII784PerioperativeEnfortumab2026siveBladderCancerVedotin4-Pembrohzumab1yrVSNeoadjuvantGemcitabineandCisplatinGYNNCT03038100Newfy-DiagnosedStageIIIorIII1301Paclitaxelcartx>platinand2023StageIVOvarian,FallopianTube,atezolizumabfor6cyclesandorPrimaryPeritonealCancerbevacizumabVSpaclitaxel,carboplatinandplaceboHeadandNeckNCTO37OO9O5HeadandNeckCancerIII276NivolumabAloneorinCombina-2024ttonWithIptlimumabasImmunotherapyVSStandardFollow-upCDS4-tumor-infiltratinglymphocytesintumortissueEvent-FreeSurvival(EFS);PathologkalCompleteResponse(pCR)OverallSurvivalEvent-FreeSurvival；PathologicalCcxnplctcResponseEvent-FreeSurvival;PathologicalCompleteResponseEvent-FreeSurvival;PathologicalCompleteResponseEvent-FreeSurvival;PathologicalCompleteResponseEvent-FreeSurvival；PathologkalCompleteResponsePFS.OSDiseaseFreeSurvivalTable1OngoingPhase3neoadjuvantchemoimmunotherapytrialsinsolidtumorsOrg^nsystemClinicaltrifllCancertypePhaseParticipantnumbersTrialdesignEstimatedstudycompletion(year)Primaryendpoint(s)LungNCT02998528(CheckMate816)EarlyStageNSCLCIII3soNivolumabPlusIpilimumabor2028Event-FreeSurvival(EFS);NivolumabPlusPtannumDou-PathologicalCompleteResponseblotChemotherapyVSPlatinumDoubletChemotherapy(PCR)NCT03456063(IMpowcr030)ResectableSlaqeII,IHA,orSelectIII453AtezolizumaborPlaceboinCom-2026EventFreeSurvivalIHBNSCLCbinationWithPlatinum-BasedChemotherapyNCT04025879(CA209-77T)SurgicallyRcmovobleEarlyStageHI452bOeoadjuvantChemotherapy2024Event-FreeSurvivalNSCLCPlusNivolumabVSNeoadjuvantChemotherapyPiusPlacebo,FollowedbySurgkaiResectionandAdjuvantTreatmentWnhNivolumaborPlaceboNCT03425643(KEYNOTE-671)ResectableStageII.IllA.andIII786PtatinumDoubletChemother-2026EventFreeSurvival;OverallSurvivalResectableIH8(T3-4N2)NSCLCapy±Pembrolizucnab(MK-3475)Neoadjuvant/AdjuvantTherapyNCT03300134(AEGEAN)ResectableStagesIIandIIINSCLCIII800Neoadjuvant/AdjuvantDur-2024Event-FreeSurvival；vdlumabfortheTreatmentofPatientsPathologicalCompleteResponseNCT051S7776ResectableLocallyAdvancedIII72NeoadjuvantSintilimaband2023PathologicallyccxnpleteresponseNSCLCHarboringnoDriverMutationsPlatinunv-basedChemotherapyrateGltractNCTO48O7673NCT04648753NCT04973306EsophagealSquamcxisCellCarcinomaResectableLocallyAdvancedThordcicEsophagealSquamcxjsCellCarcinomaEvophagealSquamousCellCarcinomaIIIIII342500176PembrolizumabPlusPaclitaxelandCisplatinVSNeoadjuvantChernoradiotherapyFollowedbySurgeryPerioperativeTortpalimab(JSOOI)CombinwiWithNeoadjuvantChemotherapyAnti-PD-1antibody(Tislelizumab,BeiGene)combinedwithneo-202820262027EventFreeSurvivalEventFreeSurvivalMajorpMhologKresponseOSadjuvantchemoradiotherapyVSneoadjuvantcl'ienxxadiotherapyfollowedbyminimallyinvasiveesophagectomyNCT043O4209ColorectalCancerIMII195NeoadjuvantSintiLmab±Chem-ocadiotherapy2026PathologiccompleteresponserateNCT02743494(CheckMate577)ResectedstageIl-IllevophagealIII794NeoadjuvantchemoRTfol-2025DiseaseFreeSurvivalorGEjuncnoncancerlowedbycompleteresection.NCT03765918(Keynote689)StageIll-IVAResectableLocore-gionallyAdvancedHeadandNeckSquamousCellCarcinomaIII704PembrolizumdbasNeoadjuvantTherapyandinCombinationWithStandardofCareasAdjuvantTherapy2026MajorPathologicalResponse(mPR);Event-freeSurvivalNCTO5125OS5OralSquamousCellCarcinomaIl-Ill80NeoadjuvantToripalimabandAlbuminPaclitaxel/CisplatmVSDocetaxel/Cisplatin/5-fluo-rouracil(TPF)onPathologicalResponseinPatients2025MajorpathologicresponseNCT045S7020High-riskNasopharyngealCarcinomaIII200ToripalimabwithneoadjuvantcisPlatinumandgemcitabineVSStandardcisPlatinumandgemcitabine2024PFSSkinNCT04949113MacroscopkStageIIIMelanomaIII420NeoadjuvantIpilimumabPlusNivolumabVSStandardAdjuvantNivolumabinMacroscopcStageIIIMelanoma2027EventFreeSurvivalNCT04949113(NADINA)StageIIIMelanomaIII420NeoadjuvantIpilimumab+Nivolumab(adjuvantNivoinresidualdisease<xdabfafenib/tremetinibinBRAFV600mut)VSStandardAdjuvantNivolumab1yr2027EventFreeSurvivalBreastNCT03725059(KEYNOTE-7S6)Earty-StageEstrogenReceptor-Positive,HumanEpidermalGrowthFactorReceptor2-Negative(ER+/HER2-)BreastCancerIII1240PemtxolizumabVSPlaceboinCombnationWithNeoadjuvantChenxitherapyandAdjuvantEndocrineTherapy2031Event-FreeSurvival;PathologicalCompleteResponseNCT03036488TripleNegativeBreastNeoplasmsIII1174PembrolizumabPlusChemotherapyVSPlaceboPlusChemotherapyasNeoadjuvantTherapyandPembrolizumabvsPlaceboasAdjuvantTherapy2025Event-FreeSurvival;PathologicalCompleteResponseNCT04613674TripleNegativeBreastCancerIII581CamrelizumabPlusChemorher-apyVSPlaceboPlusChemotherapyasNeoadjuvantTherapyi2023PathologicalcompleteresponserateNCTO262O28O(NeoTRIPaPDLl)TNBCHi278NeoadjuvantAtezolizumaborplacebowithCarbo/abraxane,surgeryfollowedbyadjuvantchemotherapy2022EventFreeSurvivalNCT03726879(IMpassionOSO)EarlyHef2+BreastCancerIII454NCT03595592(APTneo)Her2+breastcancerIII650NCT04109066(Checkmate7FL)High-risk.ER+.HER2-￡arlyBreastIIICancet1200NCT03281954TNBCIII1520NeoadjuvantAtezolizumabor2023PlacebowtihNeoadjuvantddACFollowedByTHRadjuvantAtezo1yrVSplacebowithHer2HP/TDMINeoadjuvantchemotherapy2026VSAtezolizumab+AC-TCHPVSAtezolizumab+TCHRsurgeryfollowedbyadjuvantAtezo+NCT03726879(IMpassionOSO)EarlyHef2+BreastCancerIII454NCT03595592(APTneo)Her2+breastcancerIII650NCT04109066(Checkmate7FL)High-risk.ER+.HER2-￡arlyBreastIIICancet1200NCT03281954TNBCIII1520NeoadjuvantAtezolizumabor2023PlacebowtihNeoadjuvantddACFollowedByTHRadjuvantAtezo1yrVSplacebowithHer2HP/TDMINeoadjuvantchemotherapy2026VSAtezolizumab+AC-TCHPVSAtezolizumab+TCHRsurgeryfollowedbyadjuvantAtezo+HPNivolumabVSPlaceboin2032Comb?nat?onWithNeoadjuvantChemotherapyandAdjuvantEndocrineTherapyNeoadjuvantChemotherapy2024WithAtezolizumaborPlaceboFollowedbyAdjuvantAlezoli-zumaborPlaceboPathologKdlCompleteResponseEventFreeSurvivalPathologicalCompleteResponse.EventFreeSurvivalPathologkalCompleteResponse,EventFreeSurvival表1.實體瘤領(lǐng)域正在進行的化療-免疫新輔助III期臨床研究Table2Clinicaltrialsoffirst-linetherapiesformetastatickidneycancerTrials CheckMate214Keynote426Javelin101CheckMate9ERCLEARNivolumab+lpilimumabIVPembrolizumab+AxitinibAvelumab+AxitinibNivolumab+CabozantinibPembrolizumab4-Lenvatinibq3wX4thenq4W5-10mgpobid40mgpoqd20mgpoqdNumberof10968618866511069(3arms)PatientsPrimaryORR.PFSandOSint/poorOSandPFSOSandPFSi