asco結(jié)直腸癌熱點(diǎn)薈萃北京ppt課件

1、2021 ASCO 結(jié)直腸癌熱點(diǎn)薈萃陳功中山大學(xué)腫瘤醫(yī)院2021.062021 ASCO 的CRC專場 口頭報(bào)告專場Oral session 臨床科學(xué)論壇Clinical Science Symposium (CSS) 壁報(bào)討論P(yáng)oster Discussion (PD) 教育專場Educational session (ED) 潛在可切除mCRC：MDT病例討論 ASCO/ECCO結(jié)合論壇：醫(yī)療的價(jià)值 爭辯：mCRC內(nèi)科治療中的爭議 RAS WT一線：抗VEGF vs 抗EGFR？維持治療 vs 化療假期； 部分進(jìn)展期直腸癌治療中的問題 去手術(shù)化？去新輔助治療化？輔助化療方式？ 教授有約Me

2、et The Professor (MTP) 直腸癌的影像學(xué)2021 ASCO 的CRC專場 口頭報(bào)告專場Oral session 臨床科學(xué)論壇Clinical Science Symposium (CSS) 壁報(bào)討論P(yáng)oster Discussion (PD) 教育專場Educational session (ED) 潛在可切除mCRC：MDT病例討論 爭辯：mCRC內(nèi)科治療中的爭議 RAS WT一線：抗VEGF vs 抗EGFR？維持治療 vs 化療假期； 部分進(jìn)展期直腸癌治療中的問題 去手術(shù)化？去新輔助治療化？輔助化療方式？2021 ASCO 的CRC專場 口頭報(bào)告專場Oral sess

3、ion 臨床科學(xué)論壇Clinical Science Symposium (CSS) 壁報(bào)討論P(yáng)oster Discussion (PD) 教育專場Educational session (ED) 潛在可切除mCRC：MDT病例討論 爭辯：mCRC內(nèi)科治療中的爭議 RAS WT一線：抗VEGF vs 抗EGFR？維持治療 vs 化療假期； 部分進(jìn)展期直腸癌治療中的問題 去手術(shù)化？去新輔助治療化？輔助化療方式？口頭報(bào)告專場 PART 1：Immunotherapy beyond “MSI后MSI時(shí)代的免疫治療 4個(gè)研討#3500# 3503 免疫專場：1個(gè)研討# PART 2：Side Matt

4、ers“腫瘤部位很重要 3個(gè)研討 #3504#3506 PART 3：Is Less More?“更少的治療更好？ 2個(gè)研討 #3507-#3508口頭報(bào)告專場 PART 1：Immunotherapy beyond “MSI后MSI時(shí)代的免疫治療 PART 2：Side Matters“腫瘤部位很重要 #3504：CALGB/SWOG 80405“左右半生存數(shù)據(jù)更新 #3505：美國SEER“部位與生存數(shù)據(jù)分析 #3506：原發(fā)灶部位、分子特征與EGFR單抗療效的關(guān)系 PART 3：Is Less More?“更少的治療更好？ #3507：CREST - 梗阻性左半結(jié)腸癌支架植入變急診手術(shù)為

5、擇期手術(shù) #3508：JCOG 0212 II/III期中低位直腸癌， LLND能否必要？口頭報(bào)告專場 PART 2：Side Matters“腫瘤部位很重要 #3504：CALGB/SWOG 80405“左右半生存數(shù)據(jù)更新 #3505：美國SEER“部位與生存數(shù)據(jù)分析 #3506：原發(fā)灶部位、分子特征與EGFR單抗療效的關(guān)系 PART 3：Is Less More?“更少的治療更好？ #3507：CREST - 梗阻性左半結(jié)腸癌支架植入變急診手術(shù)為擇期手術(shù) #3508：JCOG 0212 II/III期低位直腸癌， LLND能否必要？#3507 Hill et alCREST - 梗阻性結(jié)腸

6、癌支架植入變急診手術(shù)為擇期手術(shù)#3508 Fujita et alJCOG 0212: II/III期低位直腸癌LLND的必要性我的解讀 CREST： 證明了支架植入可以平安橋接，把急診手術(shù)變?yōu)閾衿谑中g(shù)，減少造口率，不影響腫瘤學(xué)效果 JCOG 0212 低位LARC，假設(shè)單純直接手術(shù)，建議LLND 未來應(yīng)該對(duì)比： TME + 術(shù)后CRT vs TME + LLND CRT + TME vs TME + LLND口頭報(bào)告專場 PART 2：Side Matters“腫瘤部位很重要 #3504：CALGB/SWOG 80405“左右半生存數(shù)據(jù)更新 #3505：美國SEER“部位與生存數(shù)據(jù)分析 #3

7、506：原發(fā)灶部位、分子特征與EGFR單抗療效的關(guān)系 PART 3：Is Less More?“更少的治療更好？ #3507：CREST - 梗阻性左半結(jié)腸癌支架植入變急診手術(shù)為擇期手術(shù) #3508：JCOG 0212 II/III期低位直腸癌， LLND能否必要？#3504 Venook et alCALGB/SWOG 80405“左右半生存數(shù)據(jù)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數(shù)據(jù)庫“CRC

27、部位與生存關(guān)系分析#3506 Lee et alEGFR單抗治療后腫瘤部位、分子特征與生存關(guān)系分析mCRC中原發(fā)灶部位的價(jià)值 預(yù)后價(jià)值： 一定的，尤其在III、IV期 左側(cè)好于右側(cè)，獨(dú)立于各種治療手段 療效預(yù)測價(jià)值：需求從以下幾個(gè)層面來搜集數(shù)據(jù) 部位與抗VEGF的療效預(yù)測 化療+VEGF單抗 vs 單純化療：AVF 2107g，NO 16966 部位與抗EGFR靶向治療的療效預(yù)測： 化療+EGFR單抗 vs 單純化療：CO 17，BOND，CRYSTAL, OPUS, PRIME RAS WT群體：化療+EGFR單抗 vs 化療+VEGF單抗 FIRE-3，CALGB/SWOG 80405，P

28、EAKmCRC中原發(fā)灶部位的價(jià)值：抗VEGF療效Loupakis et al. JNCI 2021;107(3): dju427納入三個(gè)研討的分析PROVETTAN=200治療：FOLFIRI + BevAVF2107g559治療分組： IFL BevNO 169661268治療分組：FOLFOX/XELOX BevmCRC中原發(fā)灶部位的價(jià)值：抗VEGF療效Loupakis et al. JNCI 2021;107(3): dju427mCRC中原發(fā)灶部位的價(jià)值：抗EGFR療效Brule SY. J Euro Cancer.2021;51:1405-14CO 17研討對(duì)規(guī)范治療失敗的mCRC(

29、5-FU、奧沙利鉑、伊立替康)N=572治療分組：西妥昔單抗 vs BSCmCRC中原發(fā)灶部位的價(jià)值：抗EGFR療效Brule SY. J Euro Cancer.2021;51:1405-14抗EGFR治療后，左右半結(jié)腸癌間的生存差距拉大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