肺癌生物靶向治疗进展.ppt

肺癌的生物靶向治疗进展 Current Anti-Cancer Approaches Why do we need new anticancer agents? What makes an ideal therapeutic target? Present in the majority of patients with specific tumor type Causative link with tumourigenesis Essential function in tumor cells Assessing novel targeted agents EGFR Iressa, Tarceva, C225 血管生成 Avastin COX-2 Celecoxib EGFR expression in human tumours High expression is generally associated with invasion metastasis late-stage disease chemotherapy resistance hormonal therapy resistance poor outcome EGFR highly expressed in NSCLC Extensive clinical experiencewith gefitinib Gefitinib Phase II studies: IDEAL 1 2 Tumour response: IDEAL 1 2 (250 mg/day) US EAP experience in 21064 NSCLC Characterisation of tumour response Phase III studies: INTACT 1 2 Gefitinib联合健择或诺维本一线治疗≥70岁或PS 2 NSCLC 意大利多中心II期研究 对象:≥70岁 PS 0-2,可测量病灶 方案: Gefitinib 250mg/d, 至PD A组: NVB 30mg/m2 d1,8 q21d B组: GEM 1200mg/m2 d1,8 q21d ×6周期 IRESSA联合NVB或健择治疗70岁以及老年NSCLC---II期 IRESSA+NVB IRESSA+健择 N 24 35 中位年龄 72 74 PS 0-1 96 91 鳞癌 17 31 G3/4 中 72% 11.4% 死亡 3例 0 CR/PR/SD 1/3/7 0/3/13 PD 6 9 MST 275天 275天 IRESSA对BAC的疗效-SWOG S0126 对象 138例BAC (102初治, 36二线 ）、年龄68，女性51%、PS 0/1 86% Gefitinib 500 mg 初治 RR 21%, CR 6%； MST 12月 复治 RR 10%，CR 0% ； MST 10月 1年生存 50% 女性生存16，男性 7月， p=.003 皮疹者生存12月,无皮疹5个月,p=0.01 Association between activation of ErbB pathway genes and survival following gefitinib in NSCLC 1.低pMAPK患者生存期长(p=0.02), 低ErbB2和低pMAPK联合也预测病人对Gefitinib的反应. 2.ErbB1, pAKT, Ki-67水平不能预测Gefitinib疗效 Association of papillary subtyp