1、2019 ASCO 结直肠癌热点荟萃陈功中山大学肿瘤医院2019.062019 ASCO 的CRC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 P
2、rofessor(MTP)直肠癌的影像学2019 ASCO 的CRC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？2019 ASCO 的CRC专场 口头报告专场Oral session 临床科学论坛Clinica
3、l 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#3506
4、PART 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
5、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？#3507 Hill et alCREST-梗阻性结肠癌支架植入变急诊手术为择期手术#3508 Fujita et alJCOG 02
6、12: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 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+LLND CRT+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
7、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？#3504 Venook et alCALGB/SWOG 80405“左右半”生存数据更新#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(A
8、lliance)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+Bevacizumab1ST LINEMET/ADVANCED
9、COLORECTALKRAS wtCodons 12&13FOLFIRIor FOLFOXMD choiceASCO,JUNE,2019Chemo+CetuximabChemo+CetuximabOS=29.9 mosOS=29.9 mosPFS=10.4 mosPFS=10.4 mosChemo+BevacizumabChemo+BevacizumabOS=29.0 mosOS=29.0 mosPFS=10.8 mosPFS=10.8 mosN=1137CONCLUSION:NO DIFFERENCE OS better than anticipated in both arms:Treat
10、ment effect and/or Patient selectionAll All RASRAS wt wtOS=32.0 mosOS=32.0 mosPFS=11.4 mosPFS=11.4 mosOS=31.2 mosOS=31.2 mosPFS=11.3 mosPFS=11.3 mosESMO,SEP,2019ESMO,SEP,2019N=526N=526Patient Characteristics by Tumor Side,80405(KRAS wt)RIGHT-SIDEDRIGHT-SIDED (N=293)(N=293)LEFT-SIDEDLEFT-SIDED (N=732
11、)(N=732)TOTALTOTAL*(N=1137)(N=1137)P 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 extr
12、a-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 SidednessSideSideN(N(Events)Events)Median Median(95%CI)95%CI)HRHR(95%CI)95%CI)p pLeftLeft732(732(550)550)33.333
13、.3(31.4-35.7(31.4-35.7)1.551.55(1.32-1.82)1.32-1.82)0.0001 0.0001RightRight293(293(242)242)19.419.4(16.7-23.6)16.7-23.6)RightLeft80405:OS by Sidedness(Bevacizumab)Presented by:SideSideN(N(Events)Events)Median Median(95%CI)95%CI)HR(95%CI)HR(95%CI)p pLeftLeft356(356(280)280)31.431.4(28.3-33.6)28.3-33.
14、6)1.321.32(1.05-1.65)(1.05-1.65)0.010.01RightRight150(150(121)121)24.224.2(17.9-30.3)17.9-30.3)LeftRight80405:OS by Sidedness(Cetuximab)Presented by:SideSideN(N(Events)Events)Median Median(95%CI)95%CI)HRHR(95%CI)95%CI)p pLeftLeft376(376(270)270)36.036.0(32.6-40.3)32.6-40.3)1.871.87(1.48-2.32)(1.48-2
15、.32)0.00010.0001RightRight143(143(121)121)16.716.7(13.1-19.4)13.1-19.4)LeftRight80405:Sidedness is PrognosticProgression Free Survival(PFS)Presented by:KRASKRAS wt wt N=1025 N=1025Right Right 1 1Median PFS(mos)Median PFS(mos)Left Left 1 1Median PFS(mos)Median PFS(mos)Hazard RatioHazard Ratio95%CI95%
16、CIP(adjustedP(adjusted*)AllAll pts pts8.98.911.711.71.03(1.11,1.50)1.03(1.11,1.50)P=0.0006P=0.0006Cet Cet 7.8 7.8 12.412.4 1.56(1.26,1.94)1.56(1.26,1.94)P 0.0001P 0.0001BV BV 9.69.611.2 11.2 1.06(0.86,1.31)1.06(0.86,1.31)P=0.55P=0.55*Adjusted for biologic,protocol chemotherapy,prior adjuvant therapy
17、,prior RT,age,sex,synchronous disease,in place primary,liver metastases80405:Sidedness is Prognostic Overall Survival(OS)Presented by:KRASKRAS wt wt N=1025 N=1025Right Right 1 1Median OS(mos)Median OS(mos)Left Left 1 1Median OS(mos)Median OS(mos)Hazard RatioHazard Ratio95%CI(adjusted95%CI(adjusted*)
18、P(adjustedP(adjusted*)All ptsAll pts19.419.433.333.31.55 (1.32,1.82)1.55 (1.32,1.82)P 0.0001P 0.0001Cet Cet 16.716.736.036.01.87(1.48,2.32)1.87(1.48,2.32)P 0.0001P 0.0001BevBev24.224.231.431.41.321.32(1.05,1.65)(1.05,1.65)P=0.01P=0.01*Adjusted for biologic,protocol chemotherapy,prior adjuvant therap
19、y,prior RT,age,sex,synchronous disease,in place primary,liver metastases 19.3 MONTHS IS A BIG DIFFERENCE!Median OS by Sidedness:80405 and FIRE-3*Right Right 1 1Median OS(mos)Median OS(mos)Left Left 1 1Median OS(mos)Median OS(mos)P(adjusted)P(adjusted)CALGB/SWOG 80405CALGB/SWOG 80405N=293N=293N=732N=
20、732Cet Cet 16.716.736.036.0P 0.0001P 0.0001BevBev24.224.231.431.4P=0.01P=0.01FIRE-3 FIRE-3 N=88 N=88 N=306 N=306Cet Cet 18.3 18.3 38.3 38.3 P 0.00001P 0.00001Bev Bev 23.023.028.0 28.0 P=0.038P=0.038KRASKRAS wtwtN=1025N=1025All All RASRAS wt wt N=394N=394*Sebastian Stintzing,MD,personal communication
21、 Heinemann,et al,ASCO,2019 80405:Sidedness Predictive for Biologics Biologic by 1 Side Interaction BIOLOGICBIOLOGIC SIDE SIDE OF PRIMARY OF PRIMARY HAZARDHAZARD RATIO(95%CI)RATIO(95%CI)P(adjusted P(adjusted*)Any biologic Any biologic OS and PFS OS and PFS Cetux Cetux v Bev;left v Bev;left Cetux v Be
22、v;right Cetux v Bev;right1.531.53(1.13,2.08)(1.13,2.08)P Pint int=0.005=0.005Cet vs BevCet vs Bev OSOSLeftLeft0.82 0.82(0.69,0.96)(0.69,0.96)p p=0.01=0.01PFSPFS0.84(0.72,0.98)0.84(0.72,0.98)Cet vs BevCet vs BevOSOS Right Right1.26(0.98,1.63)1.26(0.98,1.63)p=0.08 p=0.08PFSPFS1.26(1.00,1.62)1.26(1.00,
23、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 mCRC Prognostic Pts w/L-sided primary have markedly better OS than pts w/R-
24、sided primary tumor regardless of treatment arm.Predictive 1st-line Cetuximab and Bevacizumab have different treatment effects in subgroups defined by sidedness in this analysis.Presented by:Sidedness in mCRC:Biological surrogate Non-random distribution of mutations BRAF R-sided,not enough to accoun
25、t for diffference Transcriptional subtypes Hypermethylation Epiregulin,Amphiregulin Immunological effect MicrobiomePresented by:#3505 Schrag et alSEER数据库“CRC部位与生存关系分析”#3506 Lee et alEGFR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+VEG
26、F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,PRIME RAS 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 2019;107(3):dju427纳入三个研究的分析 PROVETTA N=200 治疗：FOLFIRI+Bev AVF2107g 559 治疗分组：IFL Bev NO 16966 1268 治疗分组
27、：FOLFOX/XELOX BevmCRC中原发灶部位的价值：抗VEGF疗效Loupakis et al.JNCI 2019;107(3):dju427mCRC中原发灶部位的价值：抗EGFR疗效Brule SY.J Euro Cancer.2019;51:1405-14CO 17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 vs BSCmCRC中原发灶部位的价值：抗EGFR疗效Brule SY.J Euro Cancer.2019;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 Cli
28、n Oncol 34,2019(suppl 4S;abstr 613).2.von Einem JC,et al.J Cancer Res Clin Oncol.2019;140(9):1607-1614.3.Lu HJ,et al.Asia Pac J Clin Oncol.2019 Mar 3.doi:10.1111/ajco.12469.4.Houts AC,et al.J Clin Oncol 34,2019(suppl 4S;abstr 550).5.CRYSTAL Presented at 2019 ASCO meeting.6.FIRE-3 Presented at 2019 A
29、SCO meeting.7.CALGB 80405 Presented at 2019 ASCO meeting.8.He WZ,et al.J Clin Oncol 34,2019(suppl 4S;abstr 683).9.Loupakis F,et al.J Natl Cancer Inst.2019 Feb 24;107(3).12.65.71314.414.118.518.316.436.242.82935.841.128.738.337.5051015202530354045JACCROCC-05/06#JACCROCC-05/06AIO KRK-0104Lu HJ.Asia Pa
30、c J Clin Oncol.2019 真实世界研究CRYSTALFIRE-3CALGB 80405Lu HJ.Asia Pac J Clin Oncol.2019 He WZ.J Clin Oncol.2019AVF2107gNO16966FIRE-3CALGB 80405中位OS（月）研究：人群：P值：KRAS wt1KRAS wt1KRAS wt2KRAS wt3KRAS wt4RAS wt5RAS wt6KRAS wt7KRAS wt3ITT8ITT9ITT9RAS wt6KRAS WT70.00010.00010.0010.0310.050.0030.00010.050.1680.0
31、210.05#OS数据为FOLFOX/SOX+西妥昔单抗；OS数据为FOLFOX+西妥昔单抗16.920.215.920.62324.52526.324.224.72832.1051015202530354045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
32、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 谢骑封篙尊慈榷灶琴村店矣垦桂乖新压胚奠倘擅寞侥蚀丽鉴晰溶廷箩侣郎虫林森-消化系统疾病的症状体征与检查林森-消化系统疾病的症状体征与检查
