ASCO胃肠道会议进展-张俊课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,张俊,上海交通大学医学院附属瑞金医院外科、肿瘤放化疗科,上海消化外科研究所,ASCO-GI 2011(18-20 Jan 2011,SF),ASCO,胃肠道会议进展,张俊ASCO-GI 2011(18-20 Jan 2011,Highlights of 2011 ASCO GI,结直肠癌,辅助化疗,Abstract#362,：,AVANT(XELOX+BVZ VS FOLFOX+BVZ VS FOLFOX alone),Abstract#363,：,NO147(FOLFIRIR,西妥昔单抗）,一线化疗,Abstract#365,：,NORDIC VII,（,FLOX+,西妥昔单抗一线治疗,mCRC,）,打打停停：,mCRC,标准治疗后以贝伐珠单抗卡培他滨维持治疗安全有效,Highlights of 2011 ASCO GI 结直,AVANT,：研究设计,高危,II,期,/III,期结肠癌患者行手术治疗,(N=3451),FOLFOX4,观察,随访,FOLFOX4+,贝伐单抗,贝伐单抗单药,随访,XELOX+,贝伐单抗,贝伐单抗单药,随访,Bev 5mg/kg q2w,Bev 7.5mg/kg q3w,Bev 7.5mg/kg q3w,Bev 7.5mg/kg q3w,24,周,24,周,De Gramont A,et al.2011 ASCO GI Abstract 362.,AVANT：研究设计高危II期/III期结肠癌患者行手术治疗,研究执行情况和终点指标,330 centers,34 countries,8 regions(stratified),3451 patients randomized between 20 December 2004 and 08 June 2007-2867 patients with Stage III disease,Primary endpoints(Stage III patients only):,DFS:FOLFOX4+bevacizumab vs.FOLFOX4,DFS:XELOX+bevacizumab vs.FOLFOX4,Secondary endpoints:,OS,Safety,Non-inferiority of DFS and OS for FOLFOX4+bevacizumab vs.XELOX+bevacizumab(if co-primary endpoints met),研究执行情况和终点指标330 centers,34 co,DFS(ITT Stage III)Data cut-off date:30 June 2010(3-year minimum follow-up),FOLFOX,(N=955),FOLFOX4+Bev(N=960),XELOX+Bev,(N=952),HR(95%CI),1.17,(0.98,1.39),1.07,(,0.90,1.28,),955,960,952,890,921,900,823,868,865,779,791,784,740,728,722,708,695,688,451,436,415,FOLFOX4,FOLFOX4+Bev,XELOX+Bev,Number at risk,609,586,580,282,280,268,FOLFOX4,FOLFOX4+Bev,XELOX+Bev,Event-free rate,0.0,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1.0,6,18,30,36,42,48,0,12,24,Time(months),54,60,66,72,121,123,110,0,1,0,32,33,28,0,0,0,DFS(ITT Stage III)Data cut-o,AVANT,结果小结,DFS,（至少,3,年随访期）,HR FOLFOX+BVZ 1.17(0.98,1.39),(73%3y DFS),HR XELOX+BVZ 1.07(0.9,1.28),(75%3y DFS),组间无差异,1,年的,DFS HR,结果与,NSABP-08,类似，但,1,年后消失,是否,rebound,因素？,两组的复发部位类似（,BVZ,组并未更差）,复发后的生存时间差异不大,AVANT 结果小结DFS（至少3年随访期）,Site of Recurrence(ITT Stage III),FOLFOX4,(N=955),n(%),FOLFOX4+Bev,(N=960),n(%),XELOX+Bev(N=952),n(%),Patients with tumor recurrence*,219(23),252(26),223(23),Local recurrence,39(4),42(4),47(5),Regional lymph nodes,19(2),22(2),21(2),Distant lymph nodes,36(4),31(3),30(3),Liver,82(9),87(9),62(7),Lung,45(5),63(7),57(6),Other,62(6),88(9),64(7),1 involved site,164(17),192(20),177(19),1 involved site,55(6),60(6),46(5),*And without evidence of disease at randomization;percentages based on N,Site of Recurrence(ITT Stage,Interim OS(ITT Stage III),FOLFOX,(N=955),FOLFOX4+Bev(N=960),XELOX+Bev,(N=952),HR(95%CI),1.31,(1.03,1.67),1.27,(0.99,1.62),955,960,952,914,942,920,899,925,908,884,900,894,863,869,861,844,835,840,573,573,546,FOLFOX4,FOLFOX4+Bev,XELOX+Bev,Number at risk,776,763,765,461,449,445,0.0,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1.0,6,18,30,36,42,48,0,12,24,Time(months),54,60,66,72,288,269,290,0,1,0,63,70,64,0,0,0,Event-free rate,FOLFOX4,FOLFOX4+Bev,XELOX+Bev,Interim OS(ITT Stage III)FOLF,AVANT,结果（,OS,中期数据）,HR FOLFOX+BVZ 1.31(1.03,1.67),HR FOLFOX+BVZ 1.27(0.99,1.62),是否提示,rebound,效应？,OS,数据尚未完全成熟,自复发后到死亡的时间,3,组间无差异，但,FOLFOX,组似乎更好,FOLFOX,组患者在进展后，多接受了,BVZ,的治疗，分别为,35%vs 16%,和,20%,，可能影响,OS,成绩,AVANT结果（OS 中期数据）HR FOLFOX+BVZ,NO 147,：,FOLFIRI,组数据,伊立替康为基础的方案迄今未能显示用于,CRC,辅助化疗的价值,PETACC-3,ACCORD 2,CALGB 89803,3-yr DFS,约,60%,CALGB 89803,的分子生物学分析发现与,KRAS,基因状态无关,N0147,：西妥昔单抗,+FOLFOX,数据未能显示用于辅助治疗的益处,NO147,报告,146,例,III,期,CRC,接受,FOLFIRI,（,106,）和,FOLFIRI+,西妥昔单抗（,40,）的数据,主要终点：,DFS,两组平衡好（,KRAS WT,两组均为,65%,）,NO 147：FOLFIRI组数据伊立替康为基础的方案迄今,N0147,：,2001,年的初始研究设计,R,FOLFIRI,5-FU 400 mg/m,2,+,推注,CPT-11 180 mg/m,2,+LV 400 mg/m,2,&5-FU 2400 mg/m,2,46h q2w,预计入组：,3750,例,mFOLFOX6,5-FU 400 mg/m,2,+,奥沙利铂,85 mg/m,2,+LV 400 mg/m,2,&5-FU 2400 mg/m,2,46h q2w,mFOLFOX6,FOLFIRI,Huang J,et al.2011 ASCO GI Abstract 363.,N0147：2001年的初始研究设计RFOLFIRI预计入组,N0147,：首次设计改变,2004,年,9,月添加西妥昔单抗,6,组设计,主要终点：两组,KRAS,突变型与野生型的,DFS,次要终点：,OS,，因加入西妥昔单抗而产生的,毒性反应,R,FOLFIRI,西妥昔单抗,FOLFOX,西妥昔单抗,FOLFOX,FOLFIRI,西妥昔单抗,FOLFIRI,西妥昔单抗,(C225),2011 ASCO-GI,报告,Huang J,et al.2011 ASCO GI Abstract 363.,N0147：首次设计改变 2004年9月添加西妥昔单抗RFO,与单纯,FOLFIRI,相比，,FOLFIRI,联合,C225,显著延长全组患者的,DFS,治疗组,3,年,DFS,(95%CI),HR,(95%CI),P,值,FOLFIRI,(N=106),66.7%,(58%-77%),0.44,(0.20-0.97),0.04,FOLFIRI+C225,(N=40),86.6%,(76%-98%),FOLFOX,：,75.8%,FOLFOX+C225,：,72.3%,0,12,24,36,48,60,时间,(,月,),0,20,40,60,80,100,生存和无病概率,(%),FOLFIRI,FOLFIRI+C225,n=146,Huang J,et al.2011 ASCO GI Abstract 363.,与单纯FOLFIRI相比，FOLFIRI联合C225显著延长,与单纯,FOLFIRI,相比，,FOLFIRI,联合,C225,显著延长,KRAS,野生型患者的,DFS,Huang J,et al.2011 ASCO GI Abstract 363.,FOLFOX,：,75.8%,FOLFOX+C225,：,72.3%,时间,(,月,),0,0,20,40,60,80,100,生存和无病概率,(%),12,24,36,48,60,FOLFIRI,FOLFIRI+C225,n=95,治疗组,3,年,DFS,(95%CI),HR,(95%CI),P,值,FOLFIRI,(n=60),69.8%,(60%-82%),0.31,(0.09-1.03),0.04,FOLFIRI+C225,(N=26),82.3%,(83%-100%),与单纯FOLFIRI相比，FOLFIRI联合C225显著延长,对于,KRAS,突变型患者，,FOLFIRI,联合,C225,组的,DFS,数值上高于单纯,FOLFIRI,组,治疗组,3,年,DFS,(95%CI),HR,(95%CI),P,值,FOLFIRI,(N=33),56.3%,(41%-76%),0.45,(0.13-1.53),0.19,FOLFIRI+C225,(N=13),82.5%,(63%-10