1、2022ASCO结肠癌进展结肠癌进展 南昌大学第一附属医院肿瘤科 黎军和 分子指标预测期结肠癌高危复发 大型研究结果 Ceteximab疗效的预测 结肠癌辅助化疗终点 Oxaliplatin相关 synchronous stage IV colorectal cancer 化疗策略和方案的调整 其它 分子指标预测结肠癌高危复发及指导化疗分子指标预测结肠癌高危复发及指导化疗 Abr4000 高通量高通量 Abr4001MSI Abr 4002 Abr 4012 18q LOH Background:NSABP C-01/C-02、CCF、C-04、C-06 48 genes significan
2、tly associated with recurrence risk and 66 genes predictive of 5FU/LV benefit.Multivariate analysis yielded 18 genes(7 prognostic genes,6 predictive genes,5 reference genes)and separate prognostic recurrence score(RS)and predictive treatment score(TS)algorithms.Methods:Gene expression was quantitate
3、d by RT-PCR.Recurrence-free interval(RFI),disease-free survival(DFS),and overall survival(OS)were analyzed using Cox regression Results:In the QUASAR validation study the RS predicted recurrence risk(p=0.004).The RS also predicted DFS(p=0.01)and OS(p=0.04).Recurrence risk increased monotonically wit
4、h increasing RS.In multivariate analyses,RS retained prognostic significance(p=0.008)independent of mismatch repair(MMR),T stage,nodes examined,grade,and lymphovascular invasion.MMR deficiency(p12,500 patients(pts)with stage II/III colon cancer:Findings from the ACCENT Database.Background:to determi
5、ne the impact of pts age 70 do not receive the same benefit from combination and/or oral FU as those 70.Any benefit,if present,compared to IV FU/LV would not be clinically meaningful.Tejpar etl.2022ASCO Abstract LBA4 International randomized phase III study of capecitabine(Cap),bevacizumab(Bev),and
6、mitomycin C(MMC)in first-line metastatic colorectal cancer(mCRC):Final results of the AGITG MAX trial.patients:either unfit for or who do not require initial oxaliplatin/irinotecan.Methods:arm A Cap(Cap 2000mg/m2/d or 2500mg/m2 d1-14 q21d),arm B Cap Bev(Bev 7.5mg/kg q3w)arm C Cap Bev MMC(MMC 7mg/m2
7、q6w).Results Conclusions:The addition of BevMMC to Cap significantly improved PFS without significant additional toxicity.OS was similar for all arms.Cap BevMMC is an active,low toxicity regimen that may be considered as a treatment option for pts with mCRC.Tebbutt etl.2022ASCO Abstract 4023 In phas
8、e III CRYSTAL trial，QoL was a secondary endpoint Methods:EORTC QLQ-C30(v3.0)questionnaire Results：In pts with mCRC,cetuximab plus FOLFIRI first-line significantly prolongs PFS compared with FOLFIRI alone while preserving QoL.The PFS benefit is even more pronounced for pts with KRAS wt tumors.Folprec
9、ht etl.2022ASCO Abstract 4076 mFOLFOX-bevacizumab or XELOX-bevacizumab then bevacizumab(B)alone or with erlotinib(E)in first-line treatment of patients with metastatic colorectal cancer(mCRC):Interim safety analysis of DREAM study.Results:induction with mFOLFOX-B or XELOX-B as well as maintenance wi
10、th B or B+E appears to be well-tolerated,without unexpected side effects Tournigand etl.2022ASCO Abstract 4077 Ceteximab疗效的预测疗效的预测 EGFR ligand:amphiregulin epiregulin insulin-like growth factor 1(IGF-1)BRAF-1 皮疹 EGFR polymorphisms Background:Gene expression of the EGFR ligand epiregulin(EREG)may fur
11、ther predict benefit from cetuximab Methods:CRC tumour samples were analyzed from a phase III clinical trial of cetuximab plus BSC vs BSC alone(NEJM 2022;357(20)Results:In the K-ras WT subset,OS was better for cetuximab than BSC among patients with high EREG(HR 0.43;p0.0001)but not for low EREG pati
12、ents(HR 0.77,p=0.28).High EREG AND K-ras WT status(Combimarker)was present in 139(36%).Within the Combimarker positive group the median PFS was 5.4 vs 1.9 months(HR,0.31;p0.0001),and median OS 9.8 vs 5.1 months(HR,0.43;p0.001)in the cetuximab vs BSC arms Conclusions:patients with both high EREG gene
13、 expression and K-ras wild-type status may benefit from cetuximab therapy.Determination of EREG gene expression levels should be prospectively evaluated in patient selection for EGFR targeted therapy.Jonker et al.2022ASCO Abstract 4016 Background:70%to 40%of patients with K-RAS wild type does not se
14、em to benefit from Cetuximab.Colorectal cancer cells with IGF-1 system activation may escape anti-EGFR mediated cell death Methods:IGF-1 expression and K-RAS mutational status was assessed in advanced colorectal cancer patients receiving irinotecan/cetuximab Results:IGF-1 was overexpressed in 41 cas
15、es(66%).IGF-1 negative IGF-1 positive progressive disease 6(29%)26(63%)Median TTP 7.7 months 2.3 months Among K-RAS wild type patients,IGF-1 negative and positive tumors showed a partial response to cetuximab-irinotecan in 7(50%)and 1(5%)cases respectively(p=0.004).Median TTP in IGF-1 negative tumor
16、s was 11 months and 3.2 months in IGF-1 positive colorectal cancers(p=0.03).Conclusions:IGF-1 proved to be a reliable predictive factor for resistance to anti-EGFR monoclonal antibodies in K-RAS wild type colorectal cancer Scartozzi et al.2022ASCO Abstract 4017 Background:To study the power of epiregulin(EREG)and amphiregulin(AREG)expression in primary tumors to predict the outcome in patients with chemorefractory metastatic colorectal cancer(cmCRC)treated with the combination of cetuximab plus