贝伐单抗治疗卵巢癌III期临床实验.ppt

贝伐单抗治疗卵巢癌III期临床实验 R A Burger 1M F Brady 2M A Bookman 3R A Burger 1M F Brady 2M A Bookman 3J L Walker 4H D Homesley 5J Fowler 6B J Monk 7B E Greer 8M Boente 9S X Liang101FoxChaseCancerCenter Philadelphia PA 2GynecologicOncologyGroupStatisticalandDataCenter RoswellParkCancerInstitute Buffalo NY 3UniversityofArizonaCancerCenter Tucson AZ 4UniversityofOklahomaHealthSciencesCenter OklahomaCity OK 5BrodySchoolofMedicine Greenville NC 6JamesCancerHospitalattheOhioStateUniversity Hilliard OH 7UniversityofCalifornia IrvineMedicalCenter Orange CA 8SeattleCancerCareAlliance Seattle WA 9MinnesotaOncologyandHematology Minneapolis MN 10StateUniversityofNewYorkatStonyBrook StonyBrook NY USA 贝伐单抗为人源化单克隆IgG1抗体主要作用靶点为抑制VEGF活性2004年FDA批准上市用于结直肠癌2007年Burgeretal和Cannistraetal 在JClinOncol上分别报道贝伐单抗单抗治疗复发卵巢癌II期临床实验取得较好效果2009年NCCN把贝伐单抗列为卵巢上皮性癌二线治疗內容 研究的目的 贝伐单抗联合 线化疗方案做为初始治疗方案治疗卵巢上皮癌 腹膜癌和输卵管是否能可行 4 GOG 0218 Schema Front line EpithelialOV PPorFTcancerStageIIIoptimal macroscopic StageIIIsuboptimalStageIVn 1800 planned 主要观察点 研究与对照组 PFSOverallsurvival OS safetyqualityoflifecorrelativelaboratorystudies 入组条件 HistologicdiagnosisofepithelialOV PP orFTcancerFollowingmaximaldebulkingsurgery stageIIIoptimal macroscopicresidualdisease 1cm orsuboptimal 1cm orstageIVNopriorchemotherapy1 12weeksafterinitialsurgeryGOGPS0 2NohistoryofsignificantvasculareventsNoevidenceofintestinalobstructionrequiringparenteralsupportWritteninformedconsent 入选病人情况 入选病人情况 随访观察模式 Months CP placebo BEV 6cycles Maintenanceplacebo BEV 16cycles Imaginga CA 125 Exam 9 aConventionalCTorMRI 03691215 Sameintervalsforallmodalities Every3monthsfor2years thenevery6monthsfor3years thenannually Post treatmentfollow up GOG 0218结果分析 PFS 10 CP ArmI BEV ArmII Proportionsurvivingprogressionfree Monthssincerandomization 1 00 90 80 70 60 50 40 30 20 10 0122436 11 分层分析CP BEV BEV ArmIII vsCP ArmI Treatmenthazardratio 总生存率分析AttimeoffinalPFSanalysis Proportionalive Monthssincerandomization 1 00 90 80 70 60 50 40 30 20 10 012243648 12 aStratifiedanalysis GOG 0218 MeanPatient ReportedTOIScoreDuringChemotherapy TOI TrialOutcomeIndexoftheFunctionalAssessmentofCancerTherapy Ovary FACT OTOI FACT G PhysicalWell Being 7items FunctionalWell Being 7items andtheOvarianCancerSubscale 12item 1121009080706050403020100 MeanTOIscore Randomization Pre cycle4 Pre cycle7 CP ArmI CP BEV BEV ArmIII 14 1121009080706050403020100 GOG 0218 结论 CP BEV BEV维护方案在PFS优于CP和CP BEVBEV联合 线化疗方案做为初始治疗方案治疗卵巢上皮癌 腹膜癌和输卵管癌患者时病人可以耐受 副反应与BEV单药使用相似CP BEV BEV维护方案可考虑用于卵巢上皮癌 腹膜癌和输卵管癌一线治疗 血管生成素抑制剂AMG386联合紫杉醇周疗方案治疗复发卵巢上皮癌的II期临床研究 BethY Karlan 1AmitM Oza 2VincentL Hansen 3GaryE Richardson 4DianeProvencher 5PrafullGhatage 6MarjanTassoudji 7DanielE Stepan 7DavidM Weinreich 7IgnaceB Vergote8 1Cedars SinaiMedicalCenter LosAngeles CA USA 2PrincessMargaretHospital Toronto ON Canada 3NorthernUtahAssociates Ogden UT USA 4CabriniHospital Melbourne VIC Australia 5CHUM H pitalNotre Dame Montreal QC Canada 6TomBakerCancerCentre Calgary AB Canada 7AmgenInc ThousandOaks CA USA 8UniversityHospitalLeuven EuropeanUnion 80 就诊时为晚期卵巢癌的患者将会复发并最终死亡复发后经治疗 铂类敏感患者平均PFS9 4 11 3months 铂类耐药为3 7 4 0months2 AMG386为重组的多肽溶合蛋白临床前动物实验证实AMG386能抑制移稙的生长I期临床实验显示有较的耐受性 无明显的毒副反应其中1例病人用药后一直维持PR伏态达156周以上 研究的目的 血管生成素抑制剂AMG386联合紫杉醇周疗方案治疗复发卵巢上皮癌是否影响患者的PFS其次评价疗效安全药代动力学机体抗AMG386抗体的产生 20060342研究设计 PD ArmA AMG38610mg kgIVweekly Paclitaxel ArmB AMG3863mg kgIVweekly Paclitaxel ArmC PlaceboIVweekly Paclitaxel Open labelAMG38610mg kgIVweekly Treatmentuntil ProgressiveDisease PD UnacceptabletoxicityConsentwithdrawn RANDOMIZATION Paclitaxel80mg m2IVweekly 3weekson 1weekoff Tumorassessments CTorMRIscansofthechest abdomen andpelvisevery8weeksCA 125labvalues centrallyevery8weeksandlocallyasneeded Thisstudywasconductedat38sitesin5countries161patientswererandomized 入选标准 Histologicallyorcytologicallydocumentedepithelialovarian FIGOstageII IV fallopiantube orprimaryperitonealcancerRadiographicallydocumentedprogressionperRECISTorCA 125 GCIGCriteria Measurableornon measurabledisease 3previousanticancertherapies butatleastoneplatinum containingregimenAdequaterenalandhepaticfunctionGOGperformancestatusof0or1 PFS结果 PFSisdefinedastimefromrandomizationtodiseaseprogressionperRECIST CA 125 GCIGcriteria clinicalprogression ordeath 分层PFS风险分析 HRswith80 confidenceintervals ArmA AMG38610mg kg vsArmC placebo ArmB AMG3863mg kg vsArmC placebo 影像学反应 CA 125测定 Onevaluewastruncatedat300 ie468 Onevaluewastruncatedat300 ie488 副反应 25 ofPatients 与安慰剂组相比Grade 3副反应 5 None