曲妥珠单抗Deruxtecan可有效治疗HER2阳性乳腺癌
2019-12-17   阅读:466   来源:Nejm

近日,美国纪念斯隆-凯特琳癌症中心ShanuModi联合达纳法伯癌症研究所IanKrop研究组的最新研究提出,曲妥珠单抗Deruxtecan可有效HER2阳性乳腺癌。这一研究成果于2019年12月11日发表在国际顶尖学术期刊《新英格兰医学杂志》上。

曲妥珠单抗Deruxtecan(DS-8201)是由抗HER2(人表皮生长因子受体2)抗体、可切割的四肽连接体和细胞毒性拓扑异构酶I抑制剂组成的抗体-药物偶联物。在第1阶段的剂量发现研究中,大多数HER2阳性的晚期乳腺癌患者对曲妥珠单抗Deruxtecan有效。

在这项两部分、开放标签、单组、多中心、临床2期的研究中,研究组招募了184名HER2阳性转移性乳腺癌成人患者,之前接受过曲妥珠单抗-美坦新治疗。研究的第一部分评估三种不同剂量的曲妥珠单抗Deruxtecan以确定推荐剂量;第二部分评估推荐剂量的疗效和安全性。

总体来说,184名先前平均接受过6次治疗的患者接受了推荐剂量的曲妥珠单抗Deruxtecan,即每公斤体重5.4mg。在意向治疗分析中,112名(60.9%)患者缓解。中位随访11.1个月后,中位缓解持续时间为14.8个月,无进展生存时间为16.4个月。在研究期间,最常见的3级及以上不良事件主要为中性粒细胞减少(20.7%)、贫血(8.7%)和恶心(7.6%)。经独立判断,13.6%的患者与试验药物有关。

总之,曲妥珠单抗Deruxtecan治疗HER2阳性转移性乳腺癌显示了持久的抗肿瘤活性。除恶心和骨髓抑制外,还在亚组患者中发现间质性肺疾病,需认真监测。

附:英文原文

Title:TrastuzumabDeruxtecaninPreviouslyTreatedHER2-PositiveBreastCancer|NEJM

Author:ShanuModi,M.D.,,CristinaSaura,M.D.,Ph.D.,,ToshinariYamashita,M.D.,,YeonHeePark,M.D.,,Sung-BaeKim,M.D.,Ph.D.,,KenjiTamura,M.D.,Ph.D.,,FabriceAndre,M.D.,Ph.D.,,HirojiIwata,M.D.,Ph.D.,,YoshinoriIto,M.D.,,JunjiTsurutani,M.D.,Ph.D.,,JoohyukSohn,M.D.,Ph.D.,,NeelimaDenduluri,M.D.,,ChristophePerrin,M.D.,,KenjiroAogi,M.D.,Ph.D.,,ErikoTokunaga,M.D.,,Seock-AhIm,M.D.,Ph.D.,,KeunSeokLee,M.D.,Ph.D.,,SaraA.Hurvitz,M.D.,,JavierCortes,M.D.,Ph.D.,,CalebLee,M.D.,Ph.D.,,ShuquanChen,Ph.D.,,LinZhang,M.D.,Ph.D.,,JavadShahidi,M.D.,,AntoineYver,M.D.,,andIanKrop,M.D.,Ph.D.

Issue&Volume:December11,2019

Abstract:

BACKGROUND

Trastuzumabderuxtecan(DS-8201)isanantibody-drugconjugatecomposedofananti-HER2(humanepidermalgrowthfactorreceptor2)antibody,acleavabletetrapeptide-basedlinker,andacytotoxictopoisomeraseIinhibitor.Inaphase1dose-findingstudy,amajorityofthepatientswithadvancedHER2-positivebreastcancerhadaresponsetotrastuzumabderuxtecan(medianresponseduration,20.7months).TheefficacyoftrastuzumabderuxtecaninpatientswithHER2-positivemetastaticbreastcancerpreviouslytreatedwithtrastuzumabemtansinerequiresconfirmation.

METHODS

Inthistwo-part,open-label,single-group,multicenter,phase2study,weevaluatedtrastuzumabderuxtecaninadultswithpathologicallydocumentedHER2-positivemetastaticbreastcancerwhohadreceivedprevioustreatmentwithtrastuzumabemtansine.Inthefirstpartofthestudy,weevaluatedthreedifferentdosesoftrastuzumabderuxtecantoestablisharecommendeddose;inthesecondpart,weevaluatedtheefficacyandsafetyoftherecommendeddose.Theprimaryendpointwastheobjectiveresponse,accordingtoindependentcentralreview.Keysecondaryendpointswerethedisease-controlrate,clinical-benefitrate,durationofresponseandprogression-freesurvival,andsafety.

RESULTS

Overall,184patientswhohadundergoneamedianofsixprevioustreatmentsreceivedtherecommendeddoseoftrastuzumabderuxtecan(5.4mgperkilogramofbodyweight).Intheintention-to-treatanalysis,aresponsetotherapywasreportedin112patients(60.9%;95%confidenceinterval[CI],53.4to68.0).Themediandurationoffollow-upwas11.1months(range,0.7to19.9).Themedianresponsedurationwas14.8months(95%CI,13.8to16.9),andthemediandurationofprogression-freesurvivalwas16.4months(95%CI,12.7tonotreached).Duringthestudy,themostcommonadverseeventsofgrade3orhigherwereadecreasedneutrophilcount(in20.7%ofthepatients),anemia(in8.7%),andnausea(in7.6%).Onindependentadjudication,thetrialdrugwasassociatedwithinterstitiallungdiseasein13.6%ofthepatients(grade1or2,10.9%;grade3or4,0.5%;andgrade5,2.2%).

CONCLUSIONS

TrastuzumabderuxtecanshoweddurableantitumoractivityinapretreatedpatientpopulationwithHER2-positivemetastaticbreastcancer.Inadditiontonauseaandmyelosuppression,interstitiallungdiseasewasobservedinasubgroupofpatientsandrequiresattentiontopulmonarysymptomsandcarefulmonitoring.

DOI:10.1056/NEJMoa1914510

#Deruxtecan #乳腺癌
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