asco结直肠癌热点荟萃北京课件

2016ASCO

结直肠癌热点荟萃

2016.062016ASCO的CRC专场口头报告专场Oralsession临床科学论坛ClinicalScienceSymposium(CSS)壁报讨论PosterDiscussion(PD)教育专场Educationalsession(ED)潜在可切除mCRC：MDT病例讨论ASCO/ECCO联合论坛：医疗的价值辩论：mCRC内科治疗中的争议RASWT一线：抗VEGFvs抗EGFR？维持治疗vs化疗假期；局部进展期直肠癌治疗中的问题去手术化？去新辅助治疗化？辅助化疗模式？教授有约MeetTheProfessor(MTP)直肠癌的影像学2016ASCO的CRC专场口头报告专场Oralsession临床科学论坛ClinicalScienceSymposium(CSS)壁报讨论PosterDiscussion(PD)教育专场Educationalsession(ED)潜在可切除mCRC：MDT病例讨论辩论：mCRC内科治疗中的争议RASWT一线：抗VEGFvs抗EGFR？维持治疗vs化疗假期；局部进展期直肠癌治疗中的问题去手术化？去新辅助治疗化？辅助化疗模式？口头报告专场PART1：Immunotherapybeyond“MSI后MSI时代的免疫治疗”4个研究#3500~#3503免疫专场：1个研究#PART2：SideMatters“肿瘤部位很重要”3个研究#3504~#3506PART3：IsLessMore?“更少的治疗更好？”2个研究#3507-#3508口头报告专场PART1：Immunotherapybeyond“MSI后MSI时代的免疫治疗”PART2：SideMatters“肿瘤部位很重要”#3504：CALGB/SWOG80405“左右半”生存数据更新#3505：美国SEER“部位与生存数据分析”#3506：原发灶部位、分子特征与EGFR单抗疗效的关系PART3：IsLessMore?“更少的治疗更好？”#3507：CREST-梗阻性左半结肠癌支架植入变急诊手术为择期手术#3508：JCOG0212–II/III期中低位直肠癌，LLND是否必要？口头报告专场PART2：SideMatters“肿瘤部位很重要”#3504：CALGB/SWOG80405“左右半”生存数据更新#3505：美国SEER“部位与生存数据分析”#3506：原发灶部位、分子特征与EGFR单抗疗效的关系PART3：IsLessMore?“更少的治疗更好？”#3507：CREST-梗阻性左半结肠癌支架植入变急诊手术为择期手术#3508：JCOG0212–II/III期低位直肠癌，LLND是否必要？#3508Fujitaetal

JCOG0212:II/III期低位直肠癌LLND的必要性我的解读CREST：证实了支架植入可以安全桥接，把急诊手术变为择期手术，减少造口率，不影响肿瘤学效果JCOG0212低位LARC，如果单纯直接手术，建议LLND未来应该对比：TME+术后CRTvsTME+LLNDCRT+TMEvsTME+LLND#3504Venooketal

CALGB/SWOG80405“左右半”生存数据更新#3504，Venooketal

Impactofprimarytumorlocationon

OverallSurvivalandProgressionFreeSurvival

inpatientswithmetastaticcolorectalcancer:

AnalysisofCALGB/SWOG80405(Alliance)AVenook,DNiedzwiecki,FInnocenti,BFruth,CGreene,BHO’Neil,JShaw,JAtkins,LEHorvath,BPolite,JAMeyerhardt,EMO’Reilly,RGoldberg,HSHochster,CDBlanke,RSchilsky,RJMayer,MBertagnolli,HJLenzforSWOGandtheALLIANCE80405:OverallSurvivalbySidednessSideN(Events)Median(95%CI)HR(95%CI)pLeft732(550)33.3(31.4-35.7)1.55(1.32-1.82)

<0.0001Right293(242)19.4(16.7-23.6)

RightLeft80405:OSbySidedness(Bevacizumab)

SideN(Events)Median(95%CI)HR(95%CI)pLeft356(280)31.4(28.3-33.6)1.32(1.05-1.65)

0.01

Right150(121)24.2(17.9-30.3)LeftRightPresentedby:80405:OSbySidedness(Cetuximab)SideN(Events)Median(95%CI)HR(95%CI)pLeft376(270)36.0(32.6-40.3)1.87(1.48-2.32)

<0.0001

Right143(121)16.7(13.1-19.4)LeftRightPresentedby:80405:SidednessisPrognostic

ProgressionFreeSurvival(PFS)

KRASwtN=1025Right1°MedianPFS(mos)Left1°MedianPFS(mos)HazardRatio95%CIP(adjusted*)Allpts8.911.71.03(1.11,1.50)P=0.0006Cet7.812.4

1.56(1.26,1.94)P<0.0001BV9.611.21.06(0.86,1.31)

P=0.55*Adjustedforbiologic,protocolchemotherapy,prioradjuvanttherapy,priorRT,age,sex,synchronousdisease,inplaceprimary,livermetastasesPresentedby:80405:SidednessisPrognostic

OverallSurvival(OS)

KRASwtN=1025Right1°MedianOS(mos)Left1°MedianOS(mos)HazardRatio95%CI(adjusted*)P(adjusted*)Allpts19.433.31.55(1.32,1.82)P<0.0001Cet16.736.01.87(1.48,2.32)P<0.0001Bev24.231.41.32(1.05,1.65)P=0.01*Adjustedforbiologic,protocolchemotherapy,prioradjuvanttherapy,priorRT,age,sex,synchronousdisease,inplaceprimary,livermetastases 19.3MONTHSISABIGDIFFERENCE!!Presentedby:MedianOSbySidedness:

80405andFIRE-3*

Right1°MedianOS(mos)Left1°MedianOS(mos)P(adjusted)CALGB/SWOG80405N=293N=732Cet16.736.0P<0.0001Bev24.231.4P=0.01FIRE-3N=88N=306Cet18.338.3P<0.00001Bev23.028.0P=0.038KRAS

wtN=1025AllRAS

wtN=394*SebastianStintzing,MD,personalcommunicationHeinemann,etal,ASCO,201480405:SidednessPredictiveforBiologics

Biologicby1°SideInteractionBIOLOGICSIDEOFPRIMARY

HAZARD

RATIO(95%CI)P(adjusted*)AnybiologicOSandPFSCetuxvBev;leftCetuxvBev;right1.53(1.13,2.08)Pint=0.005CetvsBev

OSLeft0.82(0.69,0.96)p=0.01PFS0.84(0.72,0.98)CetvsBevOSRight1.26(0.98,1.63)

p=0.08PFS1.26(1.00,1.62)*Adjustedforbiologic,protocolchemotherapy,prioradjuvanttherapy,priorRT,age,sex,synchronousdisease,inplaceprimary,livermetastasesOverallSurvivalbySidednessandBiologic

CALGB/SWOG80405:

SidednessinKRASwtmCRCPrognosticPtsw/L-sidedprimaryhavemarkedlybetterOSthanptsw/R-sidedprimarytumorregardlessoftreatmentarm.Predictive1st-lineCetuximabandBevacizumabhavedifferenttreatmenteffectsinsubgroupsdefinedbysidednessinthisanalysis.Presentedby:SidednessinmCRC:BiologicalsurrogateNon-randomdistributionofmutationsBRAFR-sided,notenoughtoaccountfordiffferenceTranscriptionalsubtypesHypermethylationEpiregulin,AmphiregulinImmunologicaleffectMicrobiomePresentedby:#3505Schragetal

SEER数据库“CRC部位与生存关系分析”#3506Leeetal

EGFR单抗治疗后肿瘤部位、分子特征与生存关系分析mCRC中原发灶部位的价值预后价值：肯定的，尤其在III、IV期左侧好于右侧，独立于各种治疗手段疗效预测价值：需要从以下几个层面来收集数据部位与抗VEGF的疗效预测化疗+VEGF单抗vs单纯化疗：AVF2107g，NO16966部位与抗EGFR靶向治疗的疗效预测：化疗+EGFR单抗vs单纯化疗：CO17，BOND，CRYSTAL,OPUS,PRIMERASWT群体：化疗+EGFR单抗vs化疗+VEGF单抗FIRE-3，CALGB/SWOG80405，PEAKmCRC中原发灶部位的价值：抗VEGF疗效Loupakisetal.JNCI2015;107(3):dju427纳入三个研究的分析PROVETTAN=200治疗：FOLFIRI+BevAVF2107g559治疗分组：IFL±BevNO169661268治疗分组：FOLFOX/XELOX±BevmCRC中原发灶部位的价值：抗VEGF疗效Loupakisetal.JNCI2015;107(3):dju427mCRC中原发灶部位的价值：抗EGFR疗效BruleSY.JEuroCancer.2015;51:1405-14CO17研究对标准治疗失败的mCRC(5-FU、奥沙利铂、伊立替康)N=572治疗分组：西妥昔单抗vsBSCmCRC中原发灶部位的价值：抗EGFR疗效BruleSY.JEuroCancer.2015;51:1405-14抗EGFR治疗后，左右半结肠癌间的生存差距拉大1.SunakawaY,etal.JClinOncol34,2016(suppl4S;abstr613).2.vonEinemJC,etal.JCancerResClinOncol.2014;140(9):1607-1614.3.LuHJ,etal.AsiaPacJClinOncol.2016Mar3.doi:10.1111/ajco.12469.4.HoutsAC,etal.JClinOncol34,2016(suppl4S;abstr550).5.CRYSTALPresentedat2016ASCOmeeting.6.FIRE-3Presentedat2016ASCOmeeting.7.CALGB80405Presentedat2016ASCOmeeting.8.HeWZ,etal.JClinOncol34,2016(suppl4S;abstr683).9.LoupakisF,etal.JNatlCancerInst.2015Feb24;107(3).JACCROCC-05/06#JACCROCC-05/06ωAIOKRK-0104LuHJ.AsiaPacJClinOncol.2016真实世界研究CRYSTALFIRE-3CALGB80405LuHJ.AsiaPacJClinOncol.2016HeWZ.JClinOncol.2016AVF2107gNO16966FIRE-3CALGB80405中位OS（月）