优化布局mCRC整体治疗策略的探讨ESMO指南推荐：不可切除的mCRC治疗的最终目标是延长总生存切除延长总生存并维持生活质量治疗目标期望结果长期DFS根治性手术临床表现不可切除疾病初始可切除长期疾病控制潜在可切大多患者仍为不可切除1991年：一个典型的mCRC病例4个月5-FU/LV2个月的治疗间期3个月临终前阶段2个月C.I.FU疾病进展(PD)OS11个月mCRC管理的新原则暴露于多种化疗药物与OS的延长相关不需要持续化疗直至PD治疗间期/休息期OPTIMOX/CONCEPT研究维持/重新开始治疗再次挑战模式（rechallenge）贝伐珠单抗一线治疗不可切除mCRC的疗效贝伐珠单抗一线治疗的III期研究：疗效1.Saltz,etal.JCO2008;2.Tol,etal.NEJM2009;3.Hecht,etal.JCO20094.Díaz-Rubio,etal.Oncologist2012;5.Schmoll,etal.ESMO20106.Hurwitz,etal.NEJM2004;7.Sobrero,etal.Oncology20098.Fuchs,etal.JCO2008;9.Fuchs,etal.JCO2007PACCE(n=410)3PACCE(n=410)3CAIRO-2(n=368)2CAIRO-2(n=368)2PACCE(n=115)3PACCE(n=115)3AVIRI(n=209)7AVIRI(n=209)7NO16966(n=1,400)1NO16966(n=1,400)120.320.324.524.520.520.522.222.221.3vs19.921.3vs19.9MACRO(n=239)4MACRO(n=239)423.423.4中位OS/PFS(月)中位OS/PFS(月)含伊立替康方案含伊立替康方案含奥沙利铂方案含奥沙利铂方案XELOXXELOX含奥沙利铂化疗FOLFIRI含伊立替康方案XELOX/FOLFOX4HORIZONIII(n=713)5HORIZONIII(n=713)521.321.3IFLAVF2107g(n=813)6AVF2107g(n=813)620.3vs15.620.3vs15.6BICC-C(n=57)8,9BICC-C(n=57)8,928.028.0FOLFIRIFOLFOX610.710.711.411.411.711.711.011.09.4vs8.09.4vs8.010.410.410.310.310.6vs6.210.6vs6.211.211.2++++302520151050302520151050贝伐珠单抗+OSOSPFSPFS+++与单纯化疗相比有显著性差异–与单纯化疗相比无显著性差异贝伐珠单抗治疗KRASWT患者的随机研究：疗效1.Hurwitz,etal.Oncologist2009;2.Tol,etal.NEJM2009;3.Hecht,etal.JCO20094.Reinacher-Schick,etal.ESMO2010;5.Price,etal.ESMO2010;6.Price,etal.JCO2011C=卡培他滨B=贝伐珠单抗M=丝裂霉素C=卡培他滨B=贝伐珠单抗M=丝裂霉素OSOSPFSPFS中位OS/PFS(月)中位OS/PFS(月)30302525202015151010550024.524.522.422.419.8vs20.019.8vs20.027.7vs17.627.7vs17.619.819.811.511.510.610.68.8vs5.98.8vs5.913.5vs7.413.5vs7.412.512.528.028.010.810.8Bev+XELOXBev+XELOX/XELIRIBev+伊立替康化疗Bev+IFLCB或CBMBev+奥沙利铂化疗CAIRO-22(n=156)CAIRO-22(n=156)AIO-06044(n=100)AIO-06044(n=100)AVF2107g1(n=152)AVF2107g1(n=152)PACCE3(n=203)PACCE3(n=203)PACCE3(n=58)PACCE3(n=58)AGITGMAX5,6(n=224)AGITGMAX5,6(n=224)++++++贝伐珠单抗治疗KRASMT患者的随机研究：疗效1.Hurwitz,etal.Oncologist2009;2.Tol,etal.NEJM20093.Hecht,etal.JCO2009;4.Reinacher-Schick,etal.ESMO2010OSOSPFSPFS中位OS/PFS(月)中位OS/PFS(月)303025252020151510105500Bev+XELOXBev+XELOX/XELIRIBev+伊立替康化疗Bev+奥沙利铂化疗CAIRO-22(n=108)CAIRO-22(n=108)AIO-06044(n=42)AIO-06044(n=42)AVF2107g1(n=78)AVF2107g1(n=78)PACCE3(n=125)PACCE3(n=125)PACCE3(n=39)PACCE3(n=39)++––Bev+IFL19.319.324.924.920.520.511.011.012.512.511.911.921.021.09.39.319.9vs13.619.9vs13.69.3vs5.59.3vs5.5贝伐珠单抗一线治疗mCRC小结贝伐珠单抗一线治疗的临床获益一致，与KRAS状态及联合的化疗方案无关抗EGFR抗体一线治疗不可切除mCRC的疗效CRYSTAL:西妥昔单抗联合FOLFIRI一线治疗KRASWTmCRC的III期研究VanCutsem,etal.JCO20111.00.80.60.40.201.00.80.60.40.20OS估计值OS估计值FOLFIRI(n=350)西妥昔单抗+FOLFIRI(n=316)FOLFIRI(n=350)西妥昔单抗+FOLFIRI(n=316)061218243036424854061218243036424854时间(月)时间(月)1.00.80.60.40.201.00.80.60.40.20PFS估计值PFS估计值048121620048121620时间(月)时间(月)HR=0.80p=0.009320.020.023.523.5HR=0.70p=0.00129.99.98.48.4西妥昔单抗联合奥沙利铂为基础化疗一线治疗KRASWTmCRC的II/III期研究西妥昔单抗帕尼单抗COIN2NORDICVII3PRIME1化疗CAPOX/FOL...
