。周彩存晚期非小细胞肺癌的精准治疗.pptx

周彩存周彩存，医学博士，博士生导师，主任医师，教授；上海市领军人才，享受国务院特殊津贴现任同济大学附属上海市肺科医院肿瘤科主任，医学院肿瘤研究所所长中国医促会胸部肿瘤分会主委，中国抗癌协会肺癌专业委员会常委，上海市抗癌协会肺癌分子靶向和免疫治疗专业委员会主委，中国抗癌协会肿瘤药物临床研究专业委员会副主任委员，上海市医学会分子诊断专委会副主任委员，中国医师协会肿瘤分会常委，上海市医师协会肿瘤分会副会长晚期非小细胞肺癌的精准治疗Caicun ZhouShanghai Pulmonary Hospital,Shanghai Tongji University, P.R.China肺癌是我国发病率和死亡率最高的恶性肿瘤，5年生存率仅为16％发病率和死亡率仍在上升肺癌对患者、家庭、国家都是一种灾难患 者家 庭国 家生存期短过度治疗无效治疗失去家庭成员的巨大痛苦高昂治疗费用的压力治与不治的艰难选择不断增加的高昂医疗负担肺癌驱动基因谱明确，精准治疗条件最成熟NRAS0.7%MET0.7%PIK3CA 0.8%MEK10.3%BRAF 2.6%ERBB2 2.7%ALK7.9%外显子跳跃融合基因精准治疗，路在何方？无已知的肿瘤驱动基因36%未知肺腺癌（n=200）EGFR23%点突变KRAS25%高加索肺腺癌驱动基因图谱亚裔肺腺癌驱动基因图谱Sholl LM, et al. J Thorac Oncol. 2015;10(5):768-777Seo JS, Genome Res. 2012, 22(11):2109-2119Precision Medicine in Advanced NSCLCImmunotherapy ＰＤ－Ｌ1 ＴＰＳ 50% Mutation load200 Squamous Carcinoma Smoking adenocarcinomaTarget therapy(1st, 2nd, and 3rd generation)New targets Increase of biomarker testing SCLCSquamous Ca.Adeno CaNOSLarge cell No actionabledriver mutationAvastin＋Chemo Non-squamous NSCLC Clinical Lung Cancer Genome Project and Network Genomic Medicine, Science Transl. Med. 2013US Lung Cancer Mutational Consortium (LCMC)Collaboration of 14 US Cancer CentersMultiplex genotyping of 1007 adenocarcinomas (full genotyping 733)Close link to clinical trial platform Kris et al., ASCO 2011, # 7506, Kris et al., JAMA 2014 LCMC: Benefit in overall survival for personalized treatmentKris et al., ASCO 2011, # 7506, Kris et al., JAMA 2014 IPASS开启了EGFR-TKI的肺癌精准医学时代Probabilityof PFS1.0Gefitinib EGFR M+ (n=132)Gefitinib EGFR M- (n=91)Carboplatin / paclitaxel EGFR M+ (n=129)Carboplatin / paclitaxel EGFR M- (n=85)0.8EGFR M+ HR (95% CI) 0.48 (0.36, 0.64), p0.0001EGFR M- HR (95% CI) 2.85 (2.05, 3.98), p0.00010.6Treatment by subgroup interaction test, p0.00004812162024Time from randomisation (months)Primary Cox analysis with covariates; ITT population; HR 1 implies a lower risk of progression on gefitinibMok et al 2009九项临床研究验证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1321290019