晚期NSCLC一线治疗新进展-PPT.ppt

晚晚期期NSCLCNSCLC一线一线治治疗进疗进展展 陆军军医大学新桥医院 徐 瑜 The power of teamwork 选择少：选择少：放放疗，化疗疗，化疗 肺癌：肺癌：培美曲塞培美曲塞治疗治疗非鳞非非鳞非小细胞肺癌小细胞肺癌靶向驱动基因变异靶向驱动基因变异以病理为指导以病理为指导的治疗的治疗以疾病为指导以疾病为指导的治疗的治疗以分子检测为以分子检测为指导的治疗指导的治疗临床肿瘤学临床肿瘤学 分分子肿瘤学子肿瘤学病理肿瘤学病理肿瘤学肿瘤免疫学肿瘤免疫学精准医学精准医学重建免疫监视重建免疫监视晚期NSCLC一线治疗模式演变过程以肿瘤免疫微环以肿瘤免疫微环境指导的治疗境指导的治疗Evading growth suppressor can-thanosSustaining proliferative signalAvoiding immuneDestruction Inducing angiogenesisEGFRALKROS-1Captain TKIChemo-hulkDestroyeverythingCheckpoint thorAngio-manPart1 Part1 驱动基因阳性驱动基因阳性NSCLCNSCLC治疗进展治疗进展驱动基因检测成为晚期NSCLC一线治疗前的关键步骤NCCN Clinical Practice Guidelines in Oncology(NCCN Guidelines)Non-Small Cell Lung Cancer version1.2018.研究患者人群TKI病例数PFS(月)OS(月)TKI化疗HR(95%CI)TKI化疗HR(95%CI)III期临床中EGFR突变亚组人群IPASS亚裔、不吸烟G2619.56.30.48(0.36-0.64)21.621.90.78(0.50-1.20)First Signal韩裔、不吸烟G428.06.30.61(0.31-1.22)27.225.60.82(0.352-1.922)EGFR突变人群中进行的III期临床NEJ002日本G22810.85.40.322(0.236-0.438)27.726.60.88(0.634-1.241)WJTOG3405日本G1729.66.60.52(0.378-0.715)35.538.81.185(0.767-1.829)OPTIMAL中国E15413.14.60.16(0.10-0.26)32.137.51.065ENSURE亚裔E21711.05.50.34(0.22-0.51)26.325.50.91（0.63-1.31）EURTAC高加索裔E1739.75.20.37(0.25-0.54)19.319.50.80(0.47-1.37)Lux-lung 3高加索裔、亚裔A34511.16.90.58(0.43-0.78)28.228.20.88（0.66-1.17）Lux-lung 6亚裔A36411.05.60.29(0.20-0.33)23.123.50.93（0.72-1.22）EGFR突变型晚期非鳞患者一线TKI治疗PFS更长1.Mok,et al.NEJM 2009;2.Han et al.JCO 2012.30(10).3,Maemondo,et al.NEJM 2010;4.Mitsudomi,et al.Lancet Oncol 2010;5.Zhou,et al.Lancet Oncol 2011;6.Wu YL,et al.Ann Oncol.2015.7.Rosell et al.Lancet Oncol 2012.8.CH Yang,et al.Lancet Oncol.2015.9.Wu YL,et al.Lancet Oncol 2014,15.10.BJ.Solomon,et al.NEJM 2014驱动基因的发现推进了晚期NSCLC OS的延长01234500.20.40.60.81.0Log-rank p1gene,3%MET,1%NRAS,1%MEK1,1%Keynote 407Prombro+CP（nab）vs placebo+CP（nab）鳞癌anyKeynote 189Prombro+pem+铂 vs palcebo+pem+铂 腺癌anyNivolumabBMScheckmate227Nivo+ipilimu and Nivo+chemo vs chemoNSCLCany（50%1,50%1,50%totalPD-L1HR=0.81NAHR=1.07 (NS)HR=0.69HR=0.92HR=0.81Keynote407HR=0.5658.4%vs 35%HR=0.64PD-L1Keynote189HR=0.5247.6%vs 18.9%HR=0.49PD-L1CM227PD-L11%A vs BTMB high HR=0.48NAimmatureTMB，PD-L1TMB low HR=1.17C vs BHR=0.7436.7%vs 23.1%immatureIP150ANA40%vs 41%HR=0.88(NS)Teff，PD-L1B vs CHR=0.5956%vs 41%HR=0.78IMpower131HR=0.7149%vs 41%immature(HR=0.96)PD-L1PD-L1 50%PD-L1 1%50%PD-L1 1%pembrolizumabIO+chemoIO+chemo+bevpembrolizumabIO+chemo+bevIO+chemoIO+chemo+bevIO+chemo TMB10非鳞非鳞NSCLCNSCLC一线免疫一线免疫治疗选择方案治疗选择方案鳞癌一鳞癌一线免疫线免疫治治疗选疗选择方案择方案pembrolizumabIO+chemopembrolizumabIO+chemoIO+chemoTMB10驱动基因突变型晚期NSCLC一线治疗驱动基因野生型晚期NSCLC一线治疗TupdateA+TT+CIOIO+IOIO+CIO+C+A总结To be continued.IV