晚期肺腺癌病例分享.pptx

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,#,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,2021/5/20,#,晚期肺腺癌病例分享,病 史,患者，女，,63,岁，无吸烟史，因咳嗽咳痰，痰中带血丝,2,月于,2014,年,8,月就诊，外院胸部,CT,提示右肺占位,体检：神志清，精神可，,ECOG,评分：,1,分，浅表淋巴结未及肿大，两肺呼吸音清，腹部无压痛,胸部肺,CT,示：右肺上叶前段占位，肺癌考虑，伴右肺多发结节灶、纵隔及右肺门肿大淋巴结伴胸膜小结节,上腹部,CT,提示：右肝后段包膜下异常密度灶，考虑胸膜转移头颅,MRI,及骨,ECT,均未见明显占位,2014.8.6,日右肺病灶穿刺病理示：中分化腺癌，免疫组化：,CK+,TTF-1+,CK7+,CK20-,CEA+,CDX2,局部,+,TG-,EGFR基因检测,（,ARMS,法,）,：,19外显子缺失,，,18、20、21外显子无突变,初步诊断：右肺癌伴右肺内、纵膈淋巴结、胸膜转移,（,T4N2M1,，,期）,EGFR,基因敏感突变型,2014.08.05,胸部,CT,2015,年,NCCN,指南,指南推荐，,EGFR,敏感突变患者，,一线首选,EGFR-TKI,治疗,九项临床研究验证,TKI,是,EGFR,突变阳性患者一线治疗的最佳选择,Mok et al NEJM 2009,Lee et al WCLC 2009,Mitsudomi et al Lancet Oncology 2010.,Maemondo NEJM 2010,Zhou et al ESMO 2010,Rosell Lancet Oncol 2012.,Yang JC et al ASCO 2012,Wu YL et al ASCO 2013,研究,分组,N,(EGFR m+),ORR,(%),ORR P,值,中位,PFS(,月,),PFS P,值,IPASS,易瑞沙,卡铂,/,紫杉醇,132,129,71.2,47.3,0.0001,9.5,6.3,0.0001First-SIGNAL,易瑞沙,顺铂,/,吉西他滨,26,16,84.6,37.5,0.002,8.0,6.3,0.086,WJOG3405,易瑞沙,顺铂,/,多西他赛,86,86,62.1,32.1,0.0001,9.6,6.6,0.001,NEJ002,易瑞沙,卡铂,/,紫杉醇,114,114,73.7,30.7,0.001,10.8,5.4,0.001,OPTIMAL,厄洛替尼,卡铂,/,吉西他滨,82,72,83,36,0.0001,13.1,4.6,0.0001,ENSURE,厄洛替尼,顺铂,/,吉西他滨,110,107,62.7,33.6,0.0001,11.0,5.5,0.0001,EURTAC,厄洛替尼,含铂两药,86,87,58,15,NA,9.7,5.2,0.0001,LUX-Lung,3,阿法替尼,顺铂,/,培美曲塞,230,115,56.1,22.6,0.001,11.1,6.9,0.0004,LUX-Lung 6,阿法替尼,顺铂,/,吉西他滨,242,122,66.9,23.0,0.0001,11.0,5.6,0.0001,治疗和评估,TKI,一线靶向治疗：,2014.8.14,给予,吉非替尼片,250mg,每日一次,1,月余后（,2014.9.17,）复查胸部,CT,提示：右上肺病灶明显缩小，评估,PR,，,定期复查，至,2015.5.29,胸部,CT,提示疾病进展,治疗,前,1,月,后,9,月后,4,月后,TKI,耐药后治疗,2015.11.13,奥希替尼被,FDA,批准,2015.5.31,、,7.1,给予培美曲塞,0.6g d1+,顺铂,50mg d1-2,方案化疗,2,周期,2,周期后复查,胸部,CT,提示,左肺部,明显缩小，疗效,PR,，,2.5,月后（,2015.8.17,）,复查胸部,CT,提示肺部病灶进展,TKI,耐药后治疗,化,疗,前,化疗,1,月余,后,2,月后,2.5,月,后,3,月,后,血液,EGFR,基因,检测提示,：,19,外显子,del,，,20,外显子,T790M,TKI,耐药一线化疗后处理,Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer(AURA2):a multicentre,open-label,single-arm,phase 2 study.,参加,AURA17,临床研究,，左肺肿块活检病理示腺癌，,组织,EGFR,基因,检测示：,19,外显子,del,，,20,外显子,T790M,，筛选成功于,2015.9.4,给予,AZD9291 80mg,每日一次,6,周,评估,PR,，,12,周维持,PR,18,周后,患者感纳差、腹胀，气促，乏力，体检：,ECOG,评分1-2,分，两肺呼吸音清，腹部膨隆，移动性浊音阳性，胸部,CT,提示靶病灶进展，腹部,CT,提示腹腔积液，评估,PD,，退出研究,TKI,耐药一线化疗后处理,服,AZD9291,前,服药,6,周后,AZD9291,治疗前后,服药,6,周后,服药,18,周后,AZD9291,耐药,AZD9291,耐药后腹部,CT,引流腹水找脱落细胞（制蜡块）提示低分化腺癌，组化提示：,CK+,TTF-1+,CK7,部分,+,CK20-,CEA,局部,+,TG-,NapsinA-,2016.1.12,给予顺铂,60 mg d1,8,联合人血管内皮抑制素（恩度）,60mg d1,8,腹腔化疗,2016.1.21,多西他赛,40mg d1,8,静脉化疗,+,恩度抗血管治疗，治疗后腹水消失，,2016.2.17,出现胸水，,继续顺铂联合恩度胸腔灌注，胸水消失，,1,月后（,2016.3.17,）,肺部病灶进展，腹胀明显，腹部可及包块,2016.1.16,送组织（腹水蜡块）基因检测,二代测序（,cSMART,）,:,EGFR,基因,19,外显子缺失（,36.77%,），,PIK3CA+(13.87%),AZD9291,耐药后治疗,2016.01.08,AZD9291,耐药,2016.02.17,多西他赛二线化疗后,AZD9291,耐药后治疗,2016.03.17,胸腔化疗后,腹部,CT,患者疾病迅速进展于,2016.4.12,死亡,2014.8.14-2015.5.29,：吉,非替尼一线靶向治疗：,9.5,月,2015.5.31-8.17,：,培美曲塞0.6g d1+,顺,铂5mg d1-2,化疗：,2.5,月,2015.9.4-2016.1.8,：,AZD9291,靶向治疗：,4,月,2015.1-3,：顺铂联合恩度腹腔、胸腔灌注，多西他赛化疗：,2,月,2016.4.12,：因疾病进展,死亡,Case,小结,20,个月,OS:33m vs 18m,P=0.006,PFS:15m vs 15m,P=0.65,Results:Survival(EGFR vs.EGFR+X),OA 10.06.Multiple mutations in lung cancer.Julien Mazires.,Detrimental PI3K effect on PFS when associated with EGFR mutation,OS,PFS,EGFR,vs.,EGFR+PI3K,Characteristics and Outcome of Patients with Lung Cancer Harboring Multiple Molecular Alterations:Results from the IFCT Study Biomarkers France,MDT,讨论,TKI,耐药后策略,全身化疗、继续,TKI,、局部治疗,三代,TKI,耐药机制？,手术、放疗在晚期非小细胞肺癌中的地位？,Check-point inhibition,在,EGFR,基因突变患者的地位？,Resistance mechenism of AZD9291,C797S+T790M:6/15(40%),T790M:5/15(33%),Lost T790M:4/15(27%),2017ASCO 9020#,MET amplification as a,resistance mechanism to osimertinib,Checkpoint inhibitor and EGFR mut,Thanks for your attention!,