课件：NSCLC靶向治疗.pptVIP

* 原因是后续治疗。 FLEX研究设计： 总体生存期：爱必妥联合化疗组对比单纯化疗组延长了1.2个月（11.3 对比 10.1），风险比HR=0.871，P=0.044，提示：爱必妥联合化疗对比单纯化疗显著延长所有组织学亚型患者的总生存期 这里需要强调的是：FLEX研究的入组人群包括17%的PS2分患者、94%为IV期患者、鳞癌占34%，在这样的人群中取得11.3个月的总生存，是非常有意义的！ 接受爱必妥联合化疗并且在3周之内发生皮疹的患者，中位生存期可达15个月，相比于3周内未出现皮疹的患者生存期几近翻倍（延长了6.2个月）！ . 生存优势显著，风险比HR为0.6，P0.001. Gatzemeier教授说：“这一生存期所有的区间是我们在单纯化疗的患者中看不到的！” * [slide 2] BAY 43-9006: A Novel Signal Transduction Inhibitor That Combines Two Anticancer Activities1 BAY 43-9006 is a novel signal transduction inhibitor that in preclinical models prevents tumor growth by combining two anticancer activities: inhibition of tumor cell proliferation and tumor angiogenesis. BAY 43-9006 inhibits tumor cell proliferation by targeting the RAF/MEK/ERK pathway at the level of RAF kinase. BAY 43-9006 also exerts an antiangiogenic effect by targeting the receptor tyrosine kinases VEGFR-2 and PDGFR and their associated signaling cascades. BAY 43-9006 是一种新型的信号转导抑制剂，其联合两种抗癌方式: 在临床前药理模型显示其通过联合抑制肿瘤细胞增殖和抗肿瘤血管生成两种方式来抑制肿瘤生长. BAY 43-9006通过作用于RAF激酶来 2. BAY 43-9006还通过作用于受体酪氨酸激酶血管内皮生长因子受体-2（ VEGFR-2 ）和血小板衍生生长因子受体PDGFR及其所关联的信号瀑布。也在抗血管生成上发挥作用 Reference: 1. Wilhelm S, Carter C, Tang LY, et al. BAY 43-9006 exhibits broad spectrum anti-tumor activity and targets Raf/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Clin Can Res. 2003;9 (suppl). Abstract A78. In preparation for cliical testing, the murine Ab used in the animal studies was humanized to minimize immunogenicity. As you can see from this cartoon, the entire Ab has been humanized with the exception of a small fraction in the variable region. The antibody binds all isoforms of VEGF A with high affinity and has terminal half life of 2-3 wks * * * * EML4-ALK 融合基因--NSCLC 1. Koivunen, et al. Clin Cancer Res 2008 2. Shaw, et al. ASCO 2009 3. Bang, et al. ASCO 2010 3–7% 的NSCLC 患者具有EML4-ALK 融合基因1 目前已有检测的技术 腺癌患者居多(EGFR未有突变者多见)2 Crizotinib的临床 I/II 期研究, 对于选择性的患者: DCR = 70%3 未来对于NSCLC的个体化治疗起到重大的影响 晚期NS