SimoneNEJM：NSCLC患者术前两次PD-1成功减少术后复发
的有关信息介绍如下：
2018.4.16，NEJM上发表了一篇重磅型文章。对于可手术的NSCLC患者术前进行2个周期的免疫治疗取得了非常好的效果。21例入组的患者中，有20例患者的肿瘤完全切除，一名IIIA患者因为气管侵犯而未能手术治疗。术前给予nivolumab注射，2周/次，第二次PD-1治疗与手术治疗的间隔时间平均是18天。使用PD-1治疗之后进行的影像学检查发现（还没有进行手术切除前），2名患者对PD-1治疗产生了部分应答。
18名患者病情稳定，仅仅一名患者病情进展，即疾病控制率为96%。20名可以评估的患者中有8名患者发生了临床前病理性降期（占比40%）。术后随访的一年中，20名患者中的16名患者没有复发，占比80%。18个月的无复发生存率为73%。9名患者的切除病灶出现了对PD-1的病理学应答，占比为45%。有3名患者在原发肿瘤中有完全的病理性应答。在治疗前有15个患者进行了病灶穿刺评估PD-L1表达情况，不管PD-L1表达阳性还是阴性，其实都可能会对PD-1产生病理性应答。肿瘤病灶的病理反应与治疗前的肿瘤突变负荷（TMB）存在显著的相关性。如果肿瘤突变负荷高，则患者经过PD-1治疗后的病灶残余就小。
AbstractBACKGROUNDAntibodiesthatblockprogrammeddeath1(PD-1)proteinimprovesurvivalinpatientswithadvancednon–small-celllungcancer(NSCLC)buthavenotbeentestedinresectableNSCLC,aconditioninwhichlittleprogresshasbeenmadeduringthepastdecade.METHODSInthispilotstudy,weadministeredtwopreoperativedosesofPD-1inhibitornivolumabinadultswithuntreated,surgicallyresectableearly(stageI,II,orIIIA)NSCLC.Nivolumab(atadoseof3mgperkilogramofbodyweight)wasadministeredintravenouslyevery2weeks,withsurgeryplannedapproximately4weeksafterthefirstdose.Theprimaryendpointsofthestudyweresafetyandfeasibility.Wealsoevaluatedthetumorpathologicalresponse,expressionofprogrammeddeathligand1(PD-L1),mutationalburden,andmutation-associated,neoantigen-specificT-cellresponses.RESULTSNeoadjuvantnivolumabhadanacceptableside-effectprofileandwasnotassociatedwithdelaysinsurgery.Ofthe21tumorsthatwereremoved,20werecompletelyresected.Amajorpathologicalresponseoccurredin9of20resectedtumors(45%).ResponsesoccurredinbothPD-L1–positiveandPD-L1–negativetumors.Therewasasignificantcorrelationbetweenthepathologicalresponseandthepretreatmenttumormutationalburden.ThenumberofT-cellclonesthatwerefoundinboththetumorandperipheralbloodincreasedsystemicallyafterPD-1blockadeineightofninepatientswhowereevaluated.Mutation-associated,neoantigen-specificT-cellclonesfromaprimarytumorwithacompleteresponseonpathologicalassessmentrapidlyexpandedinperipheralbloodat2to4weeksaftertreatment;
someofthesecloneswerenotdetectedbeforetheadministrationofnivolumab.CONCLUSIONSNeoadjuvantnivolumabwasassociatedwithfewsideeffects,didnotdelaysurgery,andinducedamajorpathologicalresponsein45%ofresectedtumors.ThetumormutationalburdenwaspredictiveofthepathologicalresponsetoPD-1blockade.Treatmentinducedexpansionofmutation-associated,neoantigen-specificT-cellclonesinperipheralblood.(FundedbyCancerResearchInstitute–StandUp2Cancerandothers;
ClinicalTrials.govnumber,NCT02259621.)转载于medsci.cn
