time egfr突变检测王婧主要内容.ppt

Optimal 研究设计 特罗凯150mg/天直至进展 未经化疗IIIB/IV期NSCLC EGFR基因突变 (外显子 19或L858R) ECOG PS 0–2 N=165 含铂双药化疗 R 1:1 分层因子 突变类型 组织学 吸烟状态 Act Mut+ = activating 突变s; ECOG = Eastern Cooperative Oncology 组; PS = performance status HRQoL = health-related quality of life; FACT-L = Functional Assessment of Cancer Therapy-Lung; LCSS = lung cancer symptom scale 主要终点：无进展生存(PFS) 次要终点：总生存 (OS), 客观有效率 (ORR), 疾病进展时间, 有效持续时间，, HRQoL (FACT-L, LCSS), 生物标记分析 疗效评价 每6周 Zhou, et al. ESMO 2010 OPTIMAL study ：Progression-free survival PFS probability 1.0 0.8 0.6 0.4 0.2 0 Erlotinib (n=82) Gem/carbo (n=72) HR=0.16 (0.10–0.26) Log-rank p0.0001 Time (months) 0 5 10 15 20 25 Patients at risk Erlotinib 82 70 51 20 2 0 GC 72 26 4 0 0 0 13.7 4.6 1-ys 56.9% 1-ys 1.7% 最佳肿瘤应答: OPTIMAL 20 40 60 80 100 患者 (%) CR/PR CR/PR 83% 特罗凯 (n=82) Gem/carbo (n=72) 36% 0 p0.0001 RR 特罗凯组96%的 患者 疾病控制 (CR, PR或SD) Zhou, et al. ESMO 2010 总结: OPTIMAL 对于 EGFR活化 突变的NSCLC患者，特罗凯是高效一线治疗药物 中位PFS延长三倍 (13.7 月 vs 4.6 月) 特罗凯治疗疾病进展和死亡风险降低84% (HR 0.16) 各亚组（组织学 、吸烟史、年龄、性别、疾病分期）特罗凯一线治疗均有获益 除了皮疹 (大部分为轻到中度)，特罗凯严重不良反应较化疗少 2011NCCN指南：非鳞癌一线治疗：EGFR 突变型 EGFR mutation discovered prior to first-line therapy Adapted and simplified from NSCLC NCCN Guidelines (version 3.2011) EGFR mutation discovered during chemotherapy Erlotinib Progression Second-linetherapy Add erlotinib to chemotherapy or Switchmaintenance: erlotinib Progression Second-linetherapy Interest in predictive testing for clinical outcomes with TKIs was fuelled by the discovery in 2004 of somatic mutations in the EGFR gene, in a proportion of patients with NSCLC.1,2,3 The mutations were found in the region of the gene that encodes the TK domain of the EGFR receptor. The mutations seem to be most common in women who have never smoked, and less common in Caucasian than Asian populations. The results also suggested that patients with missense mutations and deletions in the EGFR TK domain were more likely to respond to EGFR TKIs, particularly gefitinib. Overall, 81% of those with res