1、2016 ASCO 结直肠癌热点荟萃陈功中山大学肿瘤医院2016.06,2016 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 P
2、rofessor (MTP)直肠癌的影像学,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？,2016 ASCO 的CRC专场,口头报告专场Oral session 临床科学论坛Clin
3、ical 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
4、#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/
5、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？,#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 Fu
6、jita et alJCOG 0212: 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 + 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P
7、ART 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？,#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: A
8、nalysis 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 80405,Che
9、mo + Cetuximab,Chemo + Bevacizumab,1ST LINEMET / ADVANCEDCOLORECTALKRAS wtCodons 12 & 13,FOLFIRIor FOLFOXMD choice,ASCO, JUNE, 2014,Chemo + CetuximabOS = 29.9 mosPFS = 10.4 mos,Chemo + BevacizumabOS = 29.0 mosPFS = 10.8 mos,N = 1137,CONCLUSION: NO DIFFERENCE,OS better than anticipated in both arms:
10、Treatment effect and/or Patient selection,All RAS wt,OS = 32.0 mosPFS =11.4 mos,OS = 31.2 mosPFS = 11.3 mos,ESMO, SEP, 2014,N = 526,Patient Characteristics by Tumor Side, 80405 (KRAS wt),*Transverse colon 66 (excluded from analysis); unknown - 46*Test of any liver metastases versus extrahepatic,8040
11、5: Overall Survival by Sidedness,Right,Left,80405: OS by Sidedness (Bevacizumab),Presented by:,Left,Right,80405: OS by Sidedness (Cetuximab),Presented by:,Left,Right,80405: Sidedness is PrognosticProgression Free Survival (PFS),Presented by:,*Adjusted for biologic, protocol chemotherapy, prior adjuv
12、ant therapy, prior RT, age, sex , synchronous disease, in place primary, liver metastases,80405: Sidedness is Prognostic Overall Survival (OS),Presented by:,*Adjusted for biologic, protocol chemotherapy, prior adjuvant therapy, prior RT, age, sex, synchronous disease, in place primary, liver metasta
13、ses,19.3 MONTHS IS A BIG DIFFERENCE !,Median OS by Sidedness:80405 and FIRE-3*,KRAS wtN=1025,All RAS wt N=394,* Sebastian Stintzing,MD, personal communication Heinemann, et al, ASCO, 2014,80405: Sidedness Predictive for Biologics Biologic by 1 Side Interaction,*Adjusted for biologic, protocol chemot
14、herapy, 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,PrognosticPts w/ L-sided primary have markedly better OS than pts w/ R-sided primary tumor regardless of
15、treatment arm.Predictive1st-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 mutationsBRAF R-sided, not enough to account for diffference Transcriptiona
16、l subtypesHypermethylation Epiregulin, AmphiregulinImmunological effectMicrobiome,Presented 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+VEGF单抗 vs 单纯化疗：AVF 2107g，NO 16966部位与抗
17、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，PEAK,mCRC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 Bev,mCRC中原发灶部位的价值：抗VEG
18、F疗效,Loupakis et al. JNCI 2015;107(3): dju427,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,mCRC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 (supp
19、l 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 20
20、16 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).,JACCROCC-05/06#,JACCROCC-05/06,AIO KRK-0104,Lu HJ. Asia Pac J Clin Oncol. 2016,真实世界研究,CRYSTAL,FIRE-3,CALGB 80405
21、,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 wt1,KRAS wt1,KRAS wt2,KRAS wt3,KRAS wt4,RAS wt5,RAS wt6,KRAS wt7,KRAS wt3,ITT8,ITT9,ITT9,RAS wt6,KRAS WT7,0.0001,0.0001,0.001,0.031,0.05,0.003,0.0001,0.05,0.168,0.021,0.05,#OS数
22、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）,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,
