晚期非小细胞肺癌一线治疗策略课件

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,NSCLC,的一般情况,肺癌发生于支气管粘膜上皮又称支气管肺癌,是世界上最常见的恶性肿瘤之一,目前中国肺癌死亡率为,30.83/10,万，为首位恶性肿瘤死亡原因,多数病人确诊年龄为,35,75,岁，发病年龄高峰为,55,65,岁,到,2025,年，我国每年新增肺癌病例将超过,100,万，成为世界第一肺癌大国。,2009,China both sexes,NSCLC的一般情况肺癌发生于支气管粘膜上皮又称支气管肺癌2,肺癌的发病因素,吸烟，,70-87%,的肺癌患者与吸烟相关,放射性暴露因素,环境或职业暴露因素,石棉,氡,(,采矿或室内装修材料接触,),被动吸烟 大气污染,遗传,/,家族性因素,肺癌的发病因素吸烟，70-87%的肺癌患者与吸烟相关,相对发病率,（,NSCLC,非鳞癌,55%vs.,鳞癌,30,）,相对发病率（NSCLC 非鳞癌 55%vs.鳞癌 30,3,晚期,NSCLC,在非小细胞肺癌中，,60-70%,诊断时已是晚期,晚期,NSCLC,的自然病程为,4-6,月,目前被证明有效的药物,化疗药物,靶向药物,(EGFR-TKI,）,对于,鳞癌,非鳞癌,EGFR,突变型,EGFR,野生型,治疗方案的选择,晚期NSCLC在非小细胞肺癌中，60-70%诊断时已是晚期治,化疗在晚期,NSCLC,治疗地位的确立,汇聚,16,项随机对照研究，,2714,例,NSCLC,患者的荟萃分析显示：化疗有显著生存获益，,HR=0.77,，,p 0.0001,；,MST,增加,1.5,个月；,1,年生存率提高,9%,NSCLC Meta-Analyses Collaborative Group.J Clin Oncol.2019;26(28):4617-25,OS,化疗在晚期NSCLC治疗地位的确立汇聚16项随机对照研究，2,EGFR-TKI,在晚期,NSCLC,治疗的应用,ISEL,研究亚裔亚组生存期,BR.21,研究总生存期,Erlotinib vs Placebo,6.7 vs 4.7,J Thorac Oncol.2019 Oct;1(8):847-55.,Shepherd FA,et al.N Engl J Med 2019;353(2):123-32,EGFR-TKI在晚期NSCLC治疗的应用ISEL研究亚裔亚,6,化疗和,TKI,的联合,(EGFR-TKI),4项期临床研究显示厄洛替尼或吉非替尼联合化疗与单用化疗相比，未有额外临床获益,临床研究,入组人数,研究分组,PFS,/TTP,(,月,),mST(,月,),INTACT 1,1093,顺铂,+,健择,+,吉非替尼,500 mg/d,顺铂,+,健择,+,吉非替尼,250 mg/d,顺铂,+,健择,+,安慰剂,5,.5,5.8,6.0,9.9,9.9,10.9,INTACT 2,1097,卡铂,+,紫杉醇,+,吉非替尼,500 mg/d,卡铂,+,紫杉醇,+,吉非替尼,250 mg/d,卡铂,+,紫杉醇,+,安慰剂,4.6,5.3,5.0,8.7,9.8,9.9,T,RIBUTE,1059,组,1:,卡铂,+,紫杉醇,+,厄洛替尼,150 mg/d,组,2:,卡铂,+,紫杉醇,+,安慰剂,6,周后组,1,用厄洛替尼，组,2,用安慰剂维持治疗,5.1,4.9,10,.6,10.5,TALENT,1172,顺铂,+,健择,+,厄洛替尼,150 mg/d,顺铂,+,健择,+,安慰剂,6,6.2,10.8,11,Giaccone G,et al.J Clin Oncol 2019;22(5):77784.Herbst RS,et al.J Clin Oncol 2019;22(5):78594.,Herbst RS,et al.J Clin Oncol 2019;23(25):58929.,Park JO,et al.J Clin Oncol 2019;25(12):154552.,化疗和TKI的联合(EGFR-TKI)4项期临床研究显示厄,NSCLC,一线治疗的策略,先化疗还是先靶向,?,非选择人群,选择人群,(EGFR,突变,),NSCLC一线治疗的策略先化疗还是先靶向?,非选择人群,非选择人群,TKI-,化疗,VS,化疗,-TKI,一线治疗晚期,NSCLC III,期随机试验,TORCH(,非选择人群,),试验组,厄洛替尼,150mg/d,顺铂,80mg/m,2,D1,健择,1.2g/m,2,D1/8,q3w,6 cycles,标准组,顺铂,+,健择,顺铂,80mg/m,2,D1,健择,1.2g/m,2,D1/8,q3w,6 cycles,厄洛替尼,150mg/d,细胞学或组织学确诊的,IIIB*,与,IV,期,NSCLC,ECOG PS 0-1,分层因素,组织学,吸烟状态,性别,国家,年龄,种族,既往未用化疗,(,既往曾辅助化疗至少,1,年以上可入组，但需不含健择,方案,),R,PD,PD,*,锁骨上淋巴结转移或胸腔积液,ASCO 2019,C.Gridelli,et al.,Abstract#7508,TKI-化疗 VS 化疗-TKI一线治疗晚期NSCLC II,一线健择,/,顺铂治疗组的,ORR,是,一线厄洛替尼治疗组的近,3,倍,标准治疗组,(GP-E),N=380,试验组,(E-GP),N=380,客观反应率,121(32%),70(18%),健择,+,顺铂,厄洛替尼,厄洛替尼,健择,+,顺铂,一线,CR,3(1%),1(1%),一线,PR,103(27%),36(9%),二线,CR,1(1%),2(1%),二线,PR,23(6%),33(9%),无反应,259(68%),310(82%),SD,124(33%),110(29%),PD,64(17%),101(27%),NE,或脱落,71(19%),99(26%),ASCO 2019,C.Gridelli,et al.,Abstract#7508,一线健择/顺铂治疗组的ORR是一线厄洛替尼治疗组的近3,结果,-PFS,和,OS,一线化疗组,PFS,和,OS,均明显优于,TKI,组,ASCO 2019,C.Gridelli,et al.,Abstract#7508,结果-PFS和OS一线化疗组P,12,TKI vs,化疗用于一线治疗,(,非选择,人群,),一线,健择,/,顺铂治疗组,对不同亚组的治疗效果显著优于一线厄洛替尼治疗组,非选择人群一线治疗应该首选化疗,ASCO 2019,C.Gridelli,et al.,Abstract#7508,TKI vs 化疗用于一线治疗(非选择人群)一线健择/,13,选择什么化疗方案,?,生存概率,Schiller et al.,N Engl J Med,.2019;346:92-98.,ECOG1594,选择什么化疗方案?生存概率Schiller et al.N,14,健择,/铂类方案,(N=1739),其它含铂方案,(N=2510),疾病无进展生存期,(,PFS),健择,/,顺铂方案可显著降低疾病进展风险,T.Le Chevalier et al.Lung Cancer.2019;47:69-80.,5.1,月,vs.4.4,月,HR:0.88(0.82-0.93),p0.001,进展风险,12%,2019,年荟萃分析,健择/铂类方案(N=1739)疾病无进展生存期(PFS,15,健择,/顺铂方案,(N=1861),含铂其他方案,(N=2695),总生存期（,OS,）,T.Le Chevalier et al.Lung Cancer.2019;47:69-80.,9.0,月,vs.8.2,月,HR:0.90(0.84-0.96),p0.001,健择,/,顺铂方案可显著降低死亡风险,2019,年荟萃分析,死亡风险,10%,健择/顺铂方案(N=1861)总生存期（OS）T.,16,2009,年荟萃分析,明确了健择,在,三代化疗药物中的优势,研究结果：,Grossi et al,The Oncologist 2009,14(5):497-510.,0.6,0.8,1.0,1.2,1.4,G vs non-G,D vs non-D,V vs non-V,P vs non-P,O