ASCO结直肠癌热点荟萃课件

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,2019-07-29,编辑版ppt,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,7/29/2019,编辑版ppt,#,#,编辑版ppt,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Insert slide title here (max. 2 lines | max. 1 line with Action Title),ASCO,结直肠癌热点荟萃,编辑版ppt,1,2016 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 Professor (MTP,),直肠癌的影像学,编辑版ppt,2,2016 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,？,编辑版ppt,3,2016 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,？,编辑版ppt,4,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,PART 3,：,Is Less More?,“更少的治疗更好？”,2,个研究,#3507-#3508,编辑版ppt,5,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？,编辑版ppt,6,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？,编辑版ppt,7,#3507 Hill et alCREST -,梗阻,性结肠癌,支架植入变急诊手术为择期手术,编辑版ppt,8,编辑版ppt,9,编辑版ppt,10,编辑版ppt,11,编辑版ppt,12,编辑版ppt,13,#3508 Fujita et alJCOG 0212: II/III,期低位直肠癌,LLND,的必要性,编辑版ppt,14,编辑版ppt,15,编辑版ppt,16,编辑版ppt,17,编辑版ppt,18,编辑版ppt,19,编辑版ppt,20,编辑版ppt,21,编辑版ppt,22,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,编辑版ppt,23,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？,编辑版ppt,24,#3504 Venook et alCALGB/SWOG 80405“,左右半”生存数据,更新,编辑版ppt,25,#3504,，,Venook et al,Impact,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,编辑版ppt,26,CALGB/SWOG 80405,Chemo + Cetuximab,Chemo + Bevacizumab,1,ST,LINE,MET / ADVANCED,COLORECTAL,KRAS,wt,Codons 12 & 13,FOLFIRI,or,FOLFOX,MD choice,ASCO, JUNE, 2014,Chemo + Cetuximab,OS = 29.9 mos,PFS = 10.4 mos,Chemo + Bevacizumab,OS = 29.0 mos,PFS = 10.8 mos,N = 1137,CONCLUSION: NO DIFFERENCE,OS better than anticipated in both arms,:,Treatment effect and/or Patient selection,All,RAS,wt,OS = 32.0 mos,PFS =11.4 mos,OS = 31.2 mos,PFS = 11.3 mos,ESMO, SEP, 2014,N = 526,编辑版ppt,27,Patient Characteristics by Tumor Side, 80405 (KRAS wt),RIGHT-SIDED,(N = 293),LEFT-SIDED,(N = 732),TOTAL*,(N = 1137),P,Age (mean),61.2,57.3,58.4, 0.0001,Gender,(M %),54.9%,65.0 %,62.1%,0.002,Synchronous,Stage IV,86.9%,76.0%,79.3%,0.0009,Prior Adjuvant,10.6%,15.7%,14.2%,0.03,FOLFOX / FOLFIRI,74.4,/ 25.6,72.4 /,27.6,73.4 / 26.6,0.51,Primary in place,19.2%,29.6%,26.6%,0.0007,Pattern,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 extrahepatic,编辑版ppt,28,80405: Overall Survival by Sidedness,Side,N (,Events),Median,(,95% CI),HR,(,95% CI),p,Left,732 (,550),33.3,(31.4-35.7,),1.55,(,1.32-1.82), 0.0001,Right,293 (,242),19.4,(,16.7-23.6),Right,Left,编辑版ppt,29,80405: OS by Sidedness (Bevacizumab),编辑版ppt,Side,N (,Events),Median,(,95% CI),HR(95% CI),p,Left,356 (,280),31.4,(,28.3-33.6),1.32,(1.05-1.65),0.01,Right,150 (,121),24.2,(,17.9-30.3),Left,Right,30,80405: OS by Sidedness (Cetuximab,),编辑版ppt,Side,N (,Events),Median,(,95% CI),HR,(,95% CI),p,Left,376 (,270),36.0,(,32.6-40.3),1.87,(1.48-2.32),0.0001,Right,143 (,121),16.7,(,13.1-19.4),Left,Right,31,80405: Sidedness is Prognostic,Progression Free Survival (PFS),编辑版ppt,KRAS,wt,N = 1025,Right,1,Median PFS(mos),Left,1,Median PFS(mos),Hazard Ratio,95% CI,P (adjusted*),All,pts,8.9,11.7,1.03 (1.11, 1.50),P = 0.0006,Cet,7.8,12.4,1.56 (1.26, 1.94),P 0.0001,BV,9.6,11.2,1.06 (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 metastases,32,80405: Sidedness is Prognostic,Overall Survival (OS),编辑版ppt,KRAS,wt,N = 1025,Right,1,Median OS(mos),Left,1,Median OS(mos),Hazard Ratio,95% CI(adjusted*),P (adjusted*),All pts,19.4,33.3,1.55 (1.32,1.82),P 0.0001,Cet,16.7,36.0,1.87 (1.48, 2.32),P 0.0001,Bev,24.2,31.4,1.32,(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,19.3 MONTHS IS A BIG DIFFERENCE !,33,Median OS by Sidedness:,80405,and,FIRE-3*,Right,1,Median OS (mos),Left,1,Median OS (mos),P (adjusted),CALGB/SWOG 80405,N=293,N=732,Cet,16.7,36.0,P 0.0001,Bev,24.2,31.4,P = 0.01,FIRE-3,N = 88,N = 306,Cet,18.3,38.3,P 0.00001,Bev,23.0,28.0,P = 0.038,KRAS,wt,N=1025,All,RAS,wt,N=394,*,Sebastian Stintzing,MD, personal,communication,Heinemann, et al, ASCO, 2014,编辑版ppt,34,80405: Sidedness Predictive for Biologics,Biologic by 1 Side Interaction,BIOLOGIC,SIDE,OF PRIMARY,HAZARD,RATIO (95% CI),P(adjusted*),Any biologic,OS and PFS,Cetux,v Bev; left,Cetux v Bev; right,1.53,(1.13, 2.08),P,int,= 0.005,Cet vs Bev,OS,Left,0.82,(0.69, 0.96),p,= 0.01,PFS,0.84 (0.72, 0.98),Cet vs Bev,OS,Right,1.26 (0.98, 1.63),p = 0.08,PFS,1.26 (1.00, 1.62),*Adjusted for biologic, protocol chemotherapy, prior adjuvant therapy, prior RT, age, sex, synchronous disease, in place primary, liver metastases,编辑版ppt,35,Overall Survival by Sidedness and Biologic,编辑版ppt,36,CALGB/SWOG 80405:,Sidedness in,KRAS,wt mCRC,Prognostic,Pts w/ L-sided primary have markedly better OS than pts w/,R,-sided primary tumor regardless of treatment arm.,Predictive,1,st,-line Cetuximab and Bevacizumab have different treatment effects in subgroups defined by sidedness in this analysis.,编辑版ppt,37,Sidedness in mCRC: Biological surrogate,Non-random distribution of mutations,BRAF,R-sided, not enough to account for diffference,Transcriptional subtypes,Hypermethylation,Epiregulin, Amphiregulin,Immunological effect,Microbiome,编辑版ppt,38,#3505 Schrag et alSEER,数据库“,CRC,部位与生存关系分析”,编辑版ppt,39,编辑版ppt,40,编辑版ppt,41,编辑版ppt,42,编辑版ppt,43,编辑版ppt,44,编辑版ppt,45,编辑版ppt,46,编辑版ppt,47,编辑版ppt,48,编辑版ppt,49,#3506 Lee et alEGFR,单抗治疗后肿瘤部位、分子特征与生存关系分析,编辑版ppt,50,编辑版ppt,51,编辑版ppt,52,编辑版ppt,53,编辑版ppt,54,编辑版ppt,55,编辑版ppt,56,编辑版ppt,57,编辑版ppt,58,编辑版ppt,59,编辑版ppt,60,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, PRIME,RAS WT,群体：化疗,+EGFR,单抗,vs,化疗,+VEGF,单抗,FIRE-3,，,CALGB/SWOG 80405,，,PEAK,编辑版ppt,61,mCRC,中原发灶部位的价值：抗,VEGF,疗效,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：,FOLFOX/XELOX,Bev,Loupakis et al. JNCI 2015;107(3,): dju427,编辑版ppt,62,mCRC,中原发灶部位的价值：抗,VEGF,疗效,Loupakis et al. JNCI 2015;107(3,): dju427,编辑版ppt,63,mCRC,中原发灶部位的价值：抗,EGFR,疗效,Brule SY. J Euro Cancer.2015;51:1405-14,CO 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 BSC,编辑版ppt,64,mCRC,中原发灶部位的价值：抗,EGFR,疗效,Brule SY. J Euro Cancer.2015;51:1405-14,编辑版ppt,65,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).,JACCRO,CC-05/06,#,JACCRO,CC-05/06,AIO,KRK-0104,Lu HJ. Asia Pac J Clin Oncol. 2016,真实世界研究,CRYSTAL,FIRE-3,CALGB 80405,Lu HJ. Asia Pac J Clin Oncol. 2016,He WZ. J Clin Oncol . 2016,AVF2107g,NO16966,FIRE-3,CALGB 80405,中位,OS,（月）,研究：,人群：,P,值：,KRAS wt,1,KRAS wt,1,KRAS wt,2,KRAS wt,3,KRAS wt,4,RAS wt,5,RAS wt,6,KRAS wt,7,KRAS wt,3,ITT,8,ITT,9,ITT,9,RAS wt,6,KRAS WT,7,0.0001,0.0001,0.001,0.031,0.05,0.003,0.0001,0.05,0.168,0.021,0.05,#OS,数据为,FOLFOX/SOX+,西妥昔单抗；,OS,数据为,FOLFOX+,西妥昔单抗,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）,编辑版ppt,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,编辑版ppt,67,谢 谢,编辑版ppt,68,