安维汀-转移性结直肠癌靶向治疗.pptVIP

K-Raswild-types:Despitetherelativelysmallsamplesize,theOSbenefitinK-Raswild-typesisstatisticallysignificant,reflectingthe86%increasesseeninPFS.K-Rasmutants:Wedidn‘texpecttoseeabenefitbasedonthesmallsamplesize,butthehazardratioisstrong,givingastrongindicationthatifwewouldhavehadabiggersample,thedifferencewouldhavebeensignificant.Thisissupportedbystrongincreaseof60%inPFS化疗联合贝伐珠单抗后，尽管3/4级事件有所增加，但并未增加患者死亡事件的发生，60天死亡率未超过单用化疗组，说明贝伐珠单抗并未增加化疗的毒性 Lastupdated:February12,2007伐单抗（5mg/kg，1次/2周）联合IFL的一线化疗方案可显著改善转移性结直肠癌的总生存期和无进展生存期；无论KARS状态与否，患者均有临床获益；贝伐珠单抗并不加重IFL的毒性；高血压是最常见的不良反应，胃肠道穿孔罕见NO16966第一个贝伐珠单抗联合奥沙利铂为基础的III期研究。最初为两组开放性研究，比较XELOX组与FOLFOX4组的疗效，在获得贝伐珠单抗III期数据后，研究方案修定2×2析因设计，将入组的转移性结直肠癌患者随机分入XELOX组与FOLFOX4组，然后再分别分成贝伐珠单抗组与安慰剂组，主要终点是PFS。Lastupdated:August31,2007TrialNO16966metbothitsprimaryendpoints.1,2DatafortheITTpopulationshowedthatXELOXisaseffectiveintermsofprogression-freesurvivalasFOLFOX4(medianprogression-freesurvival8.0vs8.5months).1DataalsoshowedthattheadditionofAvastintochemotherapy(XELOXorFOLFOX)significantlyimprovedprogression-freesurvival(general)by20%comparedwithchemotherapyalone(medianprogression-freesurvival9.4vs8.0months).2The‘on-treatment’analysis(patientswhohaddiseaseprogressionordeathwhileonactivetreatment)showedthattheadditionofAvastintochemotherapy(XELOXorFOLFOX)significantlyimprovedmedianprogression-freesurvivalcomparedwithchemotherapyalone(10.4vs7.9months).2,3ThemagnitudeofthisbenefitissimilartothatobservedinpreviousrandomisedtrialsinwhichAvastinpluschemotherapywascomparedwithchemotherapyalone.ThesedataclearlydemonstratethatAvastinisthesuperiorregimenwhengivenuntilprogression. CI=confidenceinterval;FOLFOX=5-fluorouracil/leucovorin+oxaliplatin;HR=hazardratio;ITT=intenttotreat;PFS=progression-freesurvi