asco结直肠癌热点荟萃北京ppt课件

1、2021 ASCO 结直肠癌热点荟萃陈功中山大学肿瘤医院2021.062021 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结合论坛：医疗的价值 争辩：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； 部分进展期直肠癌治疗中的问题 去手术化？去新辅助治疗化？辅助化疗方式？ 教授有约Me

2、et The Professor (MTP) 直肠癌的影像学2021 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 争辩：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； 部分进展期直肠癌治疗中的问题 去手术化？去新辅助治疗化？辅助化疗方式？2021 ASCO 的CRC专场 口头报告专场Oral sess

3、ion 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 争辩：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； 部分进展期直肠癌治疗中的问题 去手术化？去新辅助治疗化？辅助化疗方式？口头报告专场 PART 1：Immunotherapy beyond “MSI后MSI时代的免疫治疗 4个研讨#3500# 3503 免疫专场：1个研讨# PART 2：Side Matt

4、ers“肿瘤部位很重要 3个研讨 #3504#3506 PART 3：Is Less More?“更少的治疗更好？ 2个研讨 #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

5、择期手术 #3508：JCOG 0212 II/III期中低位直肠癌， LLND能否必要？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能否必要？#3507 Hill et alCREST - 梗阻性结肠

6、癌支架植入变急诊手术为择期手术#3508 Fujita et alJCOG 0212: II/III期低位直肠癌LLND的必要性我的解读 CREST： 证明了支架植入可以平安桥接，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，假设单纯直接手术，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 #3

7、506：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能否必要？#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 met

8、astatic 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 AL

9、LIANCE CALGB/SWOG 80405Chemo + CetuximabChemo + Bevacizumab1ST LINEMET / ADVANCEDCOLORECTALKRAS wtCodons 12 & 13FOLFIRIor FOLFOXMD choiceASCO, JUNE, 2021Chemo + CetuximabChemo + CetuximabOS = 29.9 mosOS = 29.9 mosPFS = 10.4 mosPFS = 10.4 mosChemo + BevacizumabChemo + BevacizumabOS = 29.0 mosOS =

10、 29.0 mosPFS = 10.8 mosPFS = 10.8 mosN = 1CONCLUSION: NO DIFFERENCE OS better than anticipated in both arms: Treatment effect and/or Patient selectionAll RAS wtAll RAS 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, 2021ESMO, SEP

11、, 2021N = 526N = 526Patient Characteristics by Tumor Side, 80405 (KRAS wt) RIGHT-SIDEDRIGHT-SIDED (N = 293) (N = 293) LEFT-SIDEDLEFT-SIDED (N = 732) (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% 7

12、9.3%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); unk

13、nown - 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)33.333.3(31.4-35.7(31.4-35.7) )1.551.55( (1.32-1.82)1.32-1.82) 0.0001 0.0001RightRight293 (293 (2

14、42)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)28.3-33.6)1.321.32(1.05-1.65)(1.05-1.65)0.010.01RightRight150 (150 (121)12

15、1)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)(1.48-2.32)0.00010.0001RightRight143 (143 (121)121)1

16、6.716.7( (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% CIP (adjustedP (adjusted* *) )A

17、llAll 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

18、, 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(adjusted9

19、5% CI(adjusted* *) )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, prot

20、ocol chemotherapy, prior adjuvant therapy, 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 (adj

21、usted)CALGB/SWOG 80405CALGB/SWOG 80405N=293N=293N=732N=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 = 0.038KRAS wtKRAS wtN=1025N=1025All R

22、AS All RAS wt wt N=394N=394 * Sebastian Stintzing,MD, personal communication Heinemann, et al, ASCO, 2021 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* *) ) An

23、y biologic Any biologic OS and PFS OS and PFS Cetux Cetux v Bev; left v Bev; left Cetux v Bev; 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

24、.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, 1.62)*Adjusted for biologic, protocol chemotherapy, prior adjuvant therapy, prior RT, age, sex, synchronous disease, in place primary, liver metastases Overall Survival by S

25、idedness and Biologic 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 1st-line Cetuximab and Bevacizumab have different treatment effects in subgroups defined by sidedness

26、in this analysis.Presented by: 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 MicrobiomePresented by:#3505 Schrag et alSEER数据库“CRC

27、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： 一定的，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：需求从以下几个层面来搜集数据 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，P

28、EAKmCRC中原发灶部位的价值：抗VEGF疗效Loupakis et al. JNCI 2021;107(3): dju427纳入三个研讨的分析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 2021;107(3): dju427mCRC中原发灶部位的价值：抗EGFR疗效Brule SY. J Euro Cancer.2021;51:1405-14CO 17研讨对规范治疗失败的mCRC(

29、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.2021;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, 2021 (suppl 4S; abstr 613). 2. von Einem JC, et al. J Cancer Res Clin Oncol. 2021;140(9):1607-1614. 3. Lu HJ, et al. Asia Pac J Clin Oncol. 2

30、021 Mar 3. doi: 10.1111/ajco.12469. 4. Houts AC, et al. J Clin Oncol 34, 2021 (suppl 4S; abstr 550). 5. CRYSTAL Presented at 2021 ASCO meeting. 6. FIRE-3 Presented at 2021 ASCO meeting. 7. CALGB 80405 Presented at 2021 ASCO meeting. 8. He WZ, et al. J Clin Oncol 34, 2021 (suppl 4S; abstr 683). 9. Loupakis F, et al. J Natl Cancer Inst