奥希替尼的临床效果.pptVIP

21例患者参与疗效评估： 7例患者确认影像学缓解 2例患者确认CSF细胞学清除（连续两次CSF取样中未检测到肿瘤细胞） 5例患者确认神经系统功能改善 LM疗效评估 * ※ 患者因肺炎导致死亡。箭头代表在数据截止日期时的观察结果 2例患者发生导致减量的AE：1例皮肤瘙痒，1例中性粒细胞减少 Set area descriptor | Sub level 1 2015 ELCC * The drop in the KM curve at 19 月 in the 160mg arm is because for the 160mg the patient with the longest follow-up has progressed. With further follow-up we are likely not to observe this drop and the 中位 is likely to change at the moment it is very unstable and there are few patients at risk beyond 18 月. ? * *1 patient with single de novo T790M mutation without co-existing sensitising mutation, 4 patients with T790M/L858R co-existing sensitising mutation; response ongoing in 4/5 patients Data cut-off: 4 January 2016*Safety analysis set: all patients dosed ?As of June 1, 2015, of more than 1200 patients across all studies dosed with 奥希替尼, ILD grouped term events were reported in approximately 2.9% of patients (35 events): nine Grade 1,six Grade 2, 18 Grade ≥3, two currently ungraded. Of these, a 所有患者 of four?patients are reported to have died due to ILD (Grade 5) * * 第三代EGFR-TKI类药物治疗晚期非小细胞肺癌的临床观察 1.奥希替尼治疗EGFRm+晚期NSCLC的临床疗效 主要内容 2.奥希替尼和AZD3759治疗NSCLC脑转移患者的疗效 1.奥希替尼治疗EGFRm+晚期NSCLC的临床疗效 ASCO指南推荐 EGFR敏感突变NSCLC患者，一线治疗选择阿法替尼，厄罗替尼或吉非替尼。证据级别：高；推荐级别：均为高 AURA研究 ：奥希替尼一线治疗的EGFRm+晚期NSCLC临床疗效和安全性 I期：剂量爬升和扩展 首要终点：AZD9291安全性、耐受性；次要终点：MTD, PK, 有效性的初步评估 Cohort 120 mg 阳性 Cohort 240 mg Cohort 380 mg Cohort 4160 mg 阳性 阴性 阳性 阴性 阳性 阴性 剂量爬升 未进行T790M状态的筛选 剂量扩展 T790M状态由地方实验室检测后中心实验室确认（cobasTMEGFR突变检测）或中心实验室检测 Cohort 5240 mg 阳性 Rolling six design Tablet## *Paired biopsy cohort patients with T790M positive tumours; safety and efficacy data only reported here; #Prior therapy not permissible in this cohort; ##Not selected by mutation status, US only; §T790M positive from cytology specimen, Japan only T790M 人群 II期剂量扩展: AZD9291 80 mg qd治疗T790M阳性EGFR TKI治疗进展后NSCLC Cytology§ 活检* 活检* 扩展人群 I期研究 II期研究 一线EGFRm# 一线 EGFRm# Adapted from J?nne PA, et al. Ann Oncol 2015;26:(su