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免疫检查点抑制剂提高实体瘤治愈率2023有些影响因子较低又是国人常发的一些水刊存在的意义之一就是方便我梳理国内一些研究进度昨天的文章聚焦的是围术期免疫为基础的联合治疗方案失利的消息原本就是极速推进的免疫治疗,必然在校正这是既往手术、放疗、化疗、靶向治疗赛道都经历过的审慎到狂热再恢复理智的三个阶段免疫治疗已成为癌症治疗的核心支柱免疫检查点抑制剂ICIs是肿瘤免疫疗法的一个主要类别,可以重新激活先前存在的抗肿瘤免疫最初,IQ仅被批准用于化疗后或化疗同时进行的挽救治疗阶段的晚期和转移性肿瘤患者,整体有效率大约为20-30%随着十年来的重大进展,ICIs作为可切除实体瘤的新辅助和/或辅助疗法的临床试验正逐步增多这些试验取得了可喜的结果,FDA批准ICIs作为非小细胞肺癌、黑色素瘤、三阴性乳腺癌症和膀胱癌症的新辅助或辅助治疗药物,该名单还在继续增加这种治疗模式意味着癌症治疗的范式转变,因为许多早期肿瘤患者可以通过早期引入免疫治疗来获得治愈的可能这篇综述文章总结了基于ICI的免疫疗法的现状,强调了IQs作为早期肿瘤新辅助和辅助治疗的临床发展前景Fig.1FDAapprovalsoffifst-lineimmunotherapyforadvanced/metastatccancer图
1.FDA批准的用于晚期/转移性肿瘤患者一线免疫治疗方案Neoadjuvant Activated immune cells kill tumorSurgicallyremoval Adjuvant Immunotherapy、,Immunotherapy cel,sandshrinktumorst0Militateresection andprevent recurrence.星除翻AntibodiesE14Activatedimmunecellskillmore tumorcells attheSurgically removaltumorstumor bedand eradicatemicrometastasisFig.2Neoadjuvant vsAdjuvantImmunotherapyin solidtumors图
2.实体瘤领域新辅助vs辅助免疫治疗Fig.3FDA approvalsof neoadjuvantand adjuvantimmunotherapy forlocalized cancerNCTOS27O824AdvanceGastricAdenocarci III120Radicalsurgeryafterneoadjuvant2027CDS4-tumor-infiltratinglymphocytesinnoma immunotherapyalbuminPacliraxel+tumortissueSeggK+PD-1inhibitorVSadicalsurgeryafterneoad*juvantchemotherapyalbuminPachtaxel+SeggioNCT04882241GastrkCancer III120PembrolizumabMK-3475Plus2025Event-FreeSurvivalEFS;ChemotherapyXPorFPVSPldccboPlus PathologkalCompleteResponseChemotherapyXPorFPaspCROverallSurvivalNeoadjuvant/AdjuvantTreatmentGU NCT03732677MuscleInvasiveBladderCancer III988DurvdlumabinCombinationWith2026Event-FreeSurvival;Gemcitabine-4-CisplatinfoeNeoodjuvanx PathologicalCcxnplctcResponseTreatmentFollowedbyDurvalumabAloneNCT04700124MuscleInvasiveBladderCancer III784PecioperauveEnfortumabVedotinPlus2026Event-FreeSurvival;Pembrolizumab PathologicalCompleteResponseMK-3475VSNeoadjuvantGemcitabineandCisplatinNCT04209114Muscle-InvasiveBladderCancer III540NeoadjuvantandAdjuvant2024Event-FreeSurvival;MI8CWhoAreCisplatin NivolumabPlusNKTR-214,VS PathologicalCompleteResponseIneligibleNivolumabAloneVersusStandardofCareNCT04209114MI8Cineligibleforcisplatin III5402024Event-FreeSurvival;NeoadjuvantandAdjuvantNivolumab-4-PathologicalCompleteResponseBempeg/NKTR-214,VSNivolumabAlonevsStandardofCarewradicalcystectomyNCTO47OO124KEYNOTE-815CispUtirveligibleMuscleInva III784PerioperativeEnfortumab2026Event-FreeSurvival;siveBladderCancer Vedotin4-Pembrohzumab1yrVS PathologkalCompleteResponseNeoadjuvantGemcitabineandCisplatinGYNNCT03038100Newfy-DiagnosedStageIIIor III1301Paclitaxelcartxplatinand2023PFS.OSStageIVOvarian,FallopianTube,atezolizumabfor6cyclesandorPrimaryPeritonealCancer bevacizumabVSpaclitaxel,carboplatinandplaceboHeadandNeck NCTO37OO9O5HeadandNeckCancer III276NivolumabAloneorinCombina-2024DiseaseFreeSurvival图
3.FDA批准的新辅助和辅助免疫治疗研究Table1OngoingPhase3neoadjuvantchemoimmunotherapytrialsinsolidtumorsOrg^nsystem ClinicaltrifllCancertype PhaseParticipant TrialdesignPrimaryendpointsnumbers EstimatedstudycompletionyearLungNCT02998528CheckMate816EarlyStageNSCLC III3so NivolumabPlusIpilimumabor2028Event-FreeSurvivalEFS;NivolumabPlusPtannumDou-PathologicalCompleteResponseblotChemotherapyVSPlatinumDoublet PCRChemotherapyNCT03456063IMpowcr030ResectableSlaqeII,IHA,orSelect III453AtezolizumaborPlaceboinCom-2026EventFreeSurvivalIHBNSCLC binationWithPlatinum-BasedChemotherapyNCT04025879CA209-77T SurgicallyRcmovobleEarlyStageHI452bOeoadjuvantChemotherapy2024Event-FreeSurvivalNSCLC PlusNivolumabVSNeoadjuvantChemotherapyPiusPlacebo,FollowedbySurgkaiResectionandAdjuvantTreatmentWnhNivolumaborPlaceboNCT03425643KEYNOTE-671ResectableStageII.IllA.and III786PtatinumDoubletChemother-2026EventFreeSurvival;OverallSurvivalResectableIH8T3-4N2NSCLC apy±PembrolizucnabMK-3475Neoadjuvant/AdjuvantTherapyNCT03300134AEGEAN ResectableStagesIIandIIINSCLCIII800Neoadjuvant/AdjuvantDur-2024Event-FreeSurvival;vdlumabfortheTreatmentofPatients PathologicalCompleteResponseNCT051S7776ResectableLocallyAdvanced III72NeoadjuvantSintilimaband2023PathologicallyccxnpleteresponseNSCLCHarboringnoDriverMutations Platinunv-basedChemotherapy rateGltractNCTO48O7673EsophagealSquamcxisCellCarcinoma III342PembrolizumabPlusPaclitaxeland2028EventFreeSurvivalCisplatinVSNeoadjuvantChernoradiotherapyFollowedbySurgeryPerioperativeTortpalimabJSOOIResectableLocallyAdvancedThordcicNCT04648753EsophagealSquamcxjsCellCarcinoma III500CombinwiWithNeoadjuvant2026EventFreeSurvivalChemotherapyEvophagealSquamousCellCarcinomaAnti-PD-1antibodyTislelizumab,NCT04973306176BeiGenecombinedwithneo-2027MajorpMhologKresponseOSttonWithIptlimumabasImmunotherapyVSStandardFollow-upadjuvantchemoradiotherapyVSneoadjuvantclienxxadiotherapyfollowedbyminimallyinvasiveesophagectomyNCT043O4209ColorectalCancer IMII195NeoadjuvantSintiLmab±Chem-2026PathologiccompleteresponserateocadiotherapyNCT02743494CheckMate577ResectedstageIl-Illevophageal III794NeoadjuvantchemoRTfol-2025DiseaseFreeSurvivalorGEjuncnoncancer lowedbycompleteresection.NCT03765918Keynote689StageIll-IVAResectableLocore-III704PembrolizumdbasNeoadjuvant2026MajorPathologicalResponsegionallyAdvancedHeadandNeck TherapyandinCombinationWithmPR;Event-freeSurvivalSquamousCellCarcinoma StandardofCareasAdjuvantTherapyNCTO5125OS5OralSquamousCellCarcinoma Il-Ill80NeoadjuvantToripalimaband2025MajorpathologicresponseAlbuminPaclitaxel/CisplatmVSDocetaxel/Cisplatin/5-fluo-rouracilTPFonPathologicalResponseinPatientsNCT045S7020High-riskNasopharyngeal III200Toripalimabwithneoadjuvantcis2024PFSCarcinoma PlatinumandgemcitabineVSStandardcisPlatinumandgemcitabineSkinNCT04949113MacroscopkStageIIIMelanoma III420NeoadjuvantIpilimumabPlus2027EventFreeSurvivalNivolumabVSStandardAdjuvantNivolumabinMacroscopcStageIIIMelanomaNCT04949113NADINA StageIIIMelanomaIII4202027EventFreeSurvivalNeoadjuvantIpilimumab+NivolumabadjuvantNivoinresidualdiseasexdabfafenib/tremetinibinBRAFV600mutVSStandardAdjuvantNivolumab1yrBreast NCT03725059KEYNOTE-7S6Earty-StageEstrogenReceptor-III1240PemtxolizumabVSPlaceboin2031Event-FreeSurvival;Positive,HumanEpidermalGrowth CombnationWithNeoadjuvant PathologicalCompleteResponseFactorReceptor2-Negative ChenxitherapyandAdjuvantER+/HER2-BreastCancer EndocrineTherapyNCT03726879IMpassionOSOEarlyHef2+BreastCancerIII454NeoadjuvantAtezolizumabor2023Placebo PathologKdlCompleteResponsewtihNeoadjuvantddACFollowedByTHRadjuvantAtezo1yrVSplacebowithHer2HP/TDMINeoadjuvantchemotherapy2026NCT03595592APTneo Her2+breastcancer III650VSAtezolizumab+AC-TCHPVS EventFreeSurvivalAtezolizumab+TCHRsurgeryfollowedbyadjuvantAtezo+HPNivolumabVSPlaceboin2032NCT04109066Checkmate7FL High-risk.ER+.HER2-£arlyBreastIII1200Comb«nat»onWithNeoadjuvantPathologicalCompleteResponse.Cancet ChemotherapyandAdjuvantEventFreeSurvivalEndocrineTherapyNeoadjuvantChemotherapy2024WithNCT03281954TNBC III1520AtezolizumaborPlaceboFollowedby PathologkalCompleteResponse,AdjuvantAlezoli-zumaborPlacebo EventFreeSurvivalNCT03036488TripleNegativeBreastNeoplasms III11742025Event-FreeSurvival;PembrolizumabPlusChemoPathologicalCompleteResponsetherapyVSPlaceboPlusChemotherapyasNeoadjuvantTherapyandPembrolizumabvsPlaceboasAdjuvantTherapyNCT04613674TripleNegativeBreastCancer III581CamrelizumabPlusChemorher-2023PathologicalcompleteresponseapyVSPlaceboPlus rateChemotherapyasNeoadjuvantTherapyiNCTO262O28O TNBCHi278NeoadjuvantAtezolizumabor2022EventFreeSurvivalNeoTRIPaPDLlplacebowithCarbo/abraxane,surgeryfollowedbyadjuvantchemotherapyHNSCCheadnecksquamouscellcarcinom,NSCLCnon-small-celllungcancer,TNBCtriple-negativebreastcancer.OSoverallsurvival,PFSprofessionfreesurvival,VSversus表
1.实体瘤领域正在进行的化疗-免疫新辅助III期临床研究Table2Clinical trialsof first-line therapiesfor metastatickidney cancerTrialsCheckMate214Keynote426Javelin101CheckMate9ER CLEARNivolumab+lpilimumabIV Pembrolizumab+Axitinib Avelumab+Axitinib Nivolumab+Cabozantinib Pembrolizumab4-Lenvatinibq3wX4thenq4W5-10mgpobid40mgpoqd20mgpoqdNumberof109686188665110693armsPatientsPrimaryORR.PFSandOSint/poor OSandPFSOSandPFSinPD-L1+PFS PFS,OSandsafetyendpointsORR%vs42vs27593vs
35.
751.4vs
25.556vs
2771.0vs
53.3%Len+everovssunitinibCR:9vs1CR:
5.8vs
1.9CR:
4.4vs
2.1CR:8vs
536.1%sunitinib%CR%vs
16.1%vs93%vs
4.2%sunitinib%OShazard
0.
660.53-
0.
820.
530.38-
0740.
780.55-
1080.
600.40-
0.89066049-
0.88ratioPFS
12.4vs
12.
315.1vs
11.
113.8vs
8.
016.6vs
8.
323.9vs147vs92monthsHR:
0980.79-
1.23HR:
0.
690.57-
0.84HR
0.
690.56-
0.83HR:
0.
510.41-
0.64HR:
0.39vssuni-tinibGrade46vs
6362.9vs
5871.2vs
71.561vs
5182.4vs
83.1vs
71.83and4toxicity%sunitinib%Toxicity-22v
51210.7vs
13.
97.6vs
13437.2vs
14.4induceddiscontin-uation%sunitinib%FDA04/16/201804/22/201905/14/201901/21/202108/11/2021approvalORRobjectiveresponserate,PFSprogression-freesurvival,OSoverallsurvival,CRcompleteresponse,vsversus表
2.转移性肾癌一线治疗研究对于这种文章,没什么好总结的,主要就是梳理完表格就行了参考文献Ma etal.Experimental HematologyOncology202312:10https://doi.Org/
10.1186/s40164-023-00372-8。