EGFR基因突变指导TKI的治疗策略进展例析.ppt

* 应该选用何种检测方法？ * In particular, blood based (serum/plasma) testing is particularly attractive due to the ease of accessibility to samples, but the sensitivity of the methods currently used mean that identifying EGFR mutation positive patients from blood is still challenging ? AstraZeneca research suggests that of the patients who are identified as mutation positive by analysing their tumour, approximately 50% can be identified as mutation positive by analysing circulating free DNA (cfDNA) in blood. Data demonstrated a 0% false positive rate. ? For this reason, blood based testing may not replace biopsy-based testing in the near future. However, it could be used in addition to biopsy testing, for those patients for whom the physician does not have access to a sample * * * * * Internal use only Internal use only 与此同时，吉非替尼治疗EGFR基因敏感突变患者还改善了患者的生活质量。在IPASS研究EGFR基因敏感突变亚组中，吉非替尼组的生活质量改善率达到70.2%，显著高于卡铂/紫杉醇组的44.5%，提高幅度达到58% ，达到统计学显著水平，提示接受吉非替尼治疗后，更多患者获得了生活质量的改善。 与此同时，吉非替尼治疗EGFR基因敏感突变患者还改善了患者的生活质量。在IPASS研究EGFR基因敏感突变亚组中，吉非替尼组的生活质量改善率达到70.2%，显著高于卡铂/紫杉醇组的44.5%，提高幅度达到58% ，达到统计学显著水平，提示接受吉非替尼治疗后，更多患者获得了生活质量的改善，并且，在EGFR突变阳性且从吉非替尼治疗获益的患者中，生活质量(HRQoL)和症状得到改善的时间非常迅速，分别是8天和11天。 IPASS研究结果得到了其它临床研究的印证，2009年柳叶刀杂志和2010年新英格兰医学杂志分别全文发表了比较吉非替尼与标准含铂化疗一线治疗EGFR敏感基因突变患者的前瞻性多中心随机III期研究：NEJGSG002研究与WJTOG3405研究，这两项研究的设计相似，都是前瞻性地入组了EGFR基因突变的IIIB/IV期非小细胞肺癌患者，化疗方案分别为卡铂紫杉醇和顺铂多西他赛主要研究终点都是PFS。两项研究的基线特征都均衡可比，男性约30%-40%，吸烟者约30%-40%，绝大多数为腺癌。 0.52(0.378-0.715) PFS was significantly prolonged with A compared with GC by independent review (median PFS 11.0 vs 5.6 months, HR=0.28, p0.0001); Results from the investigator review were similar: HR=0.26, p0.0001, median 13.7 (A) vs 5.6 months (GC). ORR 66.9% vs 23.0%, p0.0001 DCR 92.6% vs 76.2%, p0.0001 OS (43% of events) HR=0.95, p=0.7593 IPASS IRE ≥3级皮疹3.1%，腹泻3.8%，总AE 28.7% vs 61% * LUX-LUNG3（检测方法同IPASS）：全体人群 PFS 11.1vs 6.9；19、21外显子突变13.6vs 6.9 EURTAC：conducted in 42 centres in Spain, France and Italy，platinum + docetaxel or gemcitabine. In the randomisation, pts were