ASCO结直肠癌热点荟萃北京ppt课件.pptx

2016 ASCO 2016 ASCO 结直肠癌热点荟萃结直肠癌热点荟萃陈功陈功中山大学肿瘤医院中山大学肿瘤医院2016.062016.062016 ASCO 2016 ASCO 的的CRCCRC专场专场口头报告专场Oral session 临床科学论坛Clinical Science Symposium(CSS)壁报讨论Poster Discussion(PD)教育专场Educational session(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RAS WT一线：抗VEGF vs 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Meet The Professor(MTP)直肠癌的影像学2016 ASCO 2016 ASCO 的的CRCCRC专场专场口头报告专场Oral session 临床科学论坛Clinical Science Symposium(CSS)壁报讨论Poster Discussion(PD)教育专场Educational session(ED)潜在可切除mCRC：MDT病例讨论辩论：mCRC内科治疗中的争议RAS WT一线：抗VEGF vs 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？2016 ASCO 2016 ASCO 的的CRCCRC专场专场口头报告专场Oral session 临床科学论坛Clinical Science Symposium(CSS)壁报讨论Poster Discussion(PD)教育专场Educational session(ED)潜在可切除mCRC：MDT病例讨论辩论：mCRC内科治疗中的争议RAS WT一线：抗VEGF vs 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PART 1：Immunotherapy beyond“MSI后MSI时代的免疫治疗”4个研究#3500#3503免疫专场：1个研究#PART 2：Side Matters“肿瘤部位很重要”3个研究#3504#3506PART 3：Is Less More?“更少的治疗更好？”2个研究#3507-#3508口头报告专场PART 1：Immunotherapy beyond“MSI后MSI时代的免疫治疗”PART 2：Side Matters“肿瘤部位很重要”#3504：CALGB/SWOG 80405“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PART 3：Is Less More?“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：JCOG 0212 II/III期中低位直肠癌，LLND是否必要？口头报告专场PART 2：Side Matters“肿瘤部位很重要”#3504：CALGB/SWOG 80405“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PART 3：Is Less More?“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：JCOG 0212 II/III期低位直肠癌，LLND是否必要？#3507HilletalCREST-梗阻梗阻性结肠癌性结肠癌支架植入支架植入变急诊手术为择期手术变急诊手术为择期手术#3508FujitaetalJCOG0212:II/III期低位直肠期低位直肠癌癌LLND的必要性的必要性我的解读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JCOG 0212低位LARC，如果单纯直接手术，建议LLND未来应该对比：TME+术后CRT vs TME+LLNDCRT+TME vs TME+LLND口头报告专场PART 2：Side Matters“肿瘤部位很重要”#3504：CALGB/SWOG 80405“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PART 3：Is Less More?“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：JCOG 0212 II/III期低位直肠癌，LLND是否必要？#3504VenooketalCALGB/SWOG80405“左右半左右半”生存数据生存数据更新更新#3504，Venook et alImpact of primary tumor location on Overall Survival and Progression Free Survival in patients with metastatic colorectal cancer:Analysis of CALGB/SWOG 80405(Alliance)A Venook,D Niedzwiecki,F Innocenti,B Fruth,C Greene,BH ONeil,J Shaw,J Atkins,LE Horvath,B Polite,JA Meyerhardt,EM OReilly,R Goldberg,HS Hochster,CD Blanke,R Schilsky,RJ Mayer,M Bertagnolli,HJ Lenz for SWOG and the ALLIANCE CALGB/SWOG 80405Chemo+CetuximabChemo+Bevacizumab1STLINEMET/ADVANCEDCOLORECTALKRASwtCodons12&13FOLFIRIorFOLFOXMDchoiceASCO,JUNE,2014Chemo+CetuximabOS=29.9mosPFS=10.4mosChemo+BevacizumabOS=29.0mosPFS=10.8mosN=1137CONCLUSION:NO DIFFERENCE OS better than anticipated in both arms:Treatment effect and/or Patient selectionAllRASwtOS=32.0mosPFS=11.4mosOS=31.2mosPFS=11.3mosESMO,SEP,2014N=526Patient Characteristics by Tumor Side,80405(KRAS wt)RIGHT-SIDED(N=293)LEFT-SIDED(N=732)TOTAL*(N=1137)PAge (mean)61.2 57.3 58.4 0.0001Gender(M%)54.9%65.0%62.1%0.002Synchronous Stage IV 86.9%76.0%79.3%0.0009Prior Adjuvant 10.6%15.7%14.2%0.03FOLFOX/FOLFIRI 74.4/25.6 72.4/27.6 73.4/26.60.51Primary in place 19.2%29.6%26.6%0.0007Pattern mets:liver only liver mets extra-hepatic 27.5%40.5%32.0%32.1%43.2%24.7%30.9%42.8%28.5%0.02*Transverse colon 66(excluded from analysis);unknown-46*Test of any liver metastases versus extrahepatic80405:Overall Survival by SidednessSideN(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:OS by Sidedness(Bevacizumab)Presented by:SideN(Events)Median(95%CI)HR(95%CI)pLeft356(280)31.4(28.3-33.6)1.32(1.05-1.65)0.01Right150(121)24.2(17.9-30.3)LeftRight80405:OS by Sidedness(Cetuximab)Presented by:SideN(Events)Median(95%CI)HR(95%CI)pLeft376(270)36.0(32.6-40.3)1.87(1.48-2.32)0.0001Right143(121)16.7(13.1-19.4)LeftRight80405:Sidedness is PrognosticProgression Free Survival(PFS)Presented by:KRASwtN=1025Right1MedianPFS(mos)Left1MedianPFS(mos)HazardRatio95%CIP(adjusted*)Allpts8.911.71.03(1.11,1.50)P=0.0006Cet7.812.41.56(1.26,1.94)P0.0001BV9.611.21.06(0.86,1.31)P=0.55*Adjusted for biologic,protocol chemotherapy,prior adjuvant therapy,prior RT,age,sex,synchronous disease,in place primary,liver metastases80405:Sidedness is Prognostic Overall Survival(OS)Presented by:KRASwtN=1025Right1MedianOS(mos)Left1MedianOS(mos)HazardRatio95%CI(adjusted*)P(adjusted*)Allpts19.433.31.55(1.32,1.82)P0.0001Cet16.736.01.87(1.48,2.32)P0.0001Bev24.231.41.32(1.05,1.65)P=0.01*Adjusted for biologic,protocol chemotherapy,prior adjuvant therapy,prior RT,age,sex,synchronous disease,in place primary,liver metastases 19.3MONTHSISABIGDIFFERENCE!Median OS by Sidedness:80405 and FIRE-3*Right1MedianOS(mos)Left1MedianOS(mos)P(adjusted)CALGB/SWOG80405N=293N=732Cet16.736.0P0.0001Bev24.231.4P=0.01FIRE-3N=88N=306Cet18.338.3P0.00001Bev23.028.0P=0.038KRASwtN=1025AllAllRASRASwt wt N=394N=394*Sebastian Stintzing,MD,personal communication Heinemann,et al,ASCO,2014 80405:Sidedness Predictive for Biologics Biologic by 1 Side Interaction BIOLOGICSIDEOFPRIMARYHAZARDRATIO(95%CI)P(adjusted*)AnybiologicOSandPFSCetuxvBev;leftCetuxvBev;right1.53(1.13,2.08)Pint=0.005CetvsBevOSLeft0.82(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)*Adjusted for biologic,protocol chemotherapy,prior adjuvant therapy,prior RT,age,sex,synchronous disease,in place primary,liver metastases Overall Survival by Sidedness and Biologic CALGB/SWOG 80405:Sidedness in KRAS wt mCRCPrognosticPtsw/L-sidedprimaryhavemarkedlybetterOSthanptsw/R-sidedprimarytumorregardlessoftreatmentarm.Predictive1st-lineCetuximabandBevacizumabhavedifferenttreatmenteffectsinsubgroupsdefinedbysidednessinthisanalysis.Presented by:Sidedness in mCRC:Biological surrogateNon-random distribution of mutationsBRAF R-sided,not enough to account for diffference Transcriptional subtypesHypermethylation Epiregulin,AmphiregulinImmunological effectMicrobiomePresented by:#3505SchragetalSEER数据库数据库“CRC部位与生存部位与生存关系分析关系分析”#3506LeeetalEGFR单抗治疗后肿瘤部位、分子单抗治疗后肿瘤部位、分子特征与生存关系分析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：AVF 2107g，NO 16966部位与抗EGFR靶向治疗的疗效预测：化疗+EGFR单抗 vs 单纯化疗：CO 17，BOND，CRYSTAL,OPUS,PRIMERAS WT群体：化疗+EGFR单抗 vs 化疗+VEGF单抗FIRE-3，CALGB/SWOG 80405，PEAKmCRC中原发灶部位的价值：抗VEGF疗效Loupakis et al.JNCI 2015;107(3):dju427纳入三个研究的分析PROVETTAN=200治疗：FOLFIRI+BevAVF2107g559治疗分组：IFL BevNO 169661268治疗分组：FOLFOX/XELOX BevmCRC中原发灶部位的价值：抗VEGF疗效Loupakis et al.JNCI 2015;107(3):dju427mCRC中原发灶部位的价值：抗EGFR疗效Brule SY.J Euro Cancer.2015;51:1405-14CO17研究研究对标准治疗失败的对标准治疗失败的mCRC(5-FU、奥沙利铂、伊立替康奥沙利铂、伊立替康)N=572治疗分组：治疗分组：西妥昔单西妥昔单抗抗vsBSCmCRC中原发灶部位的价值：抗EGFR疗效Brule SY.J Euro Cancer.2015;51:1405-14抗EGFR治疗后，左右半结肠癌间的生存差距拉大1.Sunakawa Y,et al.J Clin Oncol 34,2016(suppl 4S;abstr 613).2.von Einem JC,et al.J Cancer Res Clin Oncol.2014;140(9):1607-1614.3.Lu HJ,et al.Asia Pac J Clin Oncol.2016 Mar 3.doi:10.1111/ajco.12469.4.Houts AC,et al.J Clin Oncol 34,2016(suppl 4S;abstr 550).5.CRYSTAL Presented at 2016 ASCO meeting.6.FIRE-3 Presented at 2016 ASCO meeting.7.CALGB 80405 Presented at 2016 ASCO meeting.8.He WZ,et al.J Clin Oncol 34,2016(suppl 4S;abstr 683).9.Loupakis F,et al.J Natl Cancer Inst.2015 Feb 24;107(3).05101520253035404512.65.71314.414.118.518.316.436.242.82935.841.128.738.337.5JACCROCC-05/06#JACCROCC-05/06AIO KRK-0104Lu HJ.Asia Pac J Clin Oncol.2016 真实世界研究CRYSTALFIRE-3CALGB 80405Lu HJ.Asia Pac J Clin Oncol.2016 He WZ.J Clin Oncol.2016AVF2107gNO16966FIRE-3CALGB 80405中位OS（月）研究：人群：P值：KRAS wt1KRAS wt1KRAS wt2KRAS wt3KRAS wt4RAS wt5RAS wt6KRAS wt7KRAS wt3ITT8ITT9ITT9RAS wt6KRAS WT70.0001 0.00010.0010.0310.050.0030.00010.050.1680.0210.05#OS数据为FOLFOX/SOX+西妥昔单抗；OS数据为FOLFOX+西妥昔单抗45403530252015105016.920.215.920.62324.52526.324.224.72832.1右半结肠癌（西妥昔单抗联合化疗）左半结(直)肠癌（西妥昔单抗联合化疗）右半结肠癌（贝伐珠单抗联合化疗）左半结(直)肠癌（贝伐珠单抗联合化疗）mCRC中原发灶部位的预测价值：小结疗效预测价值：部位与抗VEGF的疗效预测不是疗效预测指标：部位与抗VEGF疗效无关部位与抗EGFR靶向治疗的疗效预测：潜在的替代标志（生物学行为、分子通路）部位可能是疗效预测指标：现有数据(CO 17)，等待更多数据(BOND，CRYSTAL,OPUS,PRIME)右侧结肠也许是EGFR independent：对EGFR单抗治疗获益很小/无效？RAS之外的另一个？RAS WT群体：化疗+EGFR单抗 vs 化疗+VEGF单抗现有数据表明：左半结肠，Cet对比Bev具有明显生存优势；右半结肠，Bev对比Cet具有生存优势一线选择：当两个靶向药物均可以选择时，右半优先推荐Bev，左半优先推荐Cet治疗选择还要考虑其他因素：毒性、耐受性、对其他治疗的干扰（如手术）、经济、个人意愿谢 谢