1晚期NSCLC治疗的变革.pptVIP

KIF5B-RET融合 在不吸烟的白人NSCLC中的突变率约2% 可能对舒尼替尼、索拉非尼和凡德他尼敏感，需要前瞻性临床研究进行验证 KIF5B-RET融合致癌活动可抑制 NSCLC治疗指南的改写 2009年NCCN治疗指南 2009年TKI尚未进入NCCN一线治疗推荐 2010年NCCN治疗指南 2010年TKI进入了NCCN一线治疗推荐 2011年NCCN治疗指南 2011年NCCN指南在推荐腺癌患者常规进行EGFR基因突变检测，阳性患者一线使用TKI。 2012年NCCN治疗指南 2012年NCCN指南在推荐常规EGFR突变检测指导一线治疗之外，加入了ALK的检测推荐。 总结 NSCLC的治疗从病理分型时代进入了分子分型时代。 随着EGFR、ALK、KARS、CMET等基因及其药物的发现，肺癌的治疗将根据其肿瘤驱动基因的异常，个体化地选择靶向药物治疗。其中，目前唯一能够在临床上指导治疗的就是EGFR基因突变。 为了在提高治疗效果同时，给肿瘤患者更高的生活质量，生存的尊严。 需要对所有晚期NSCLC患者进行EGFR基因突变检测，按照结果选择一线治疗方案。 谢 谢！ * Reference Lynch TJ et al. N Engl J Med 2004; 350: 2129-2139. The timelines for three key Phase III trials with IRESSA in NSCLC are shown here: ISEL1, INTEREST2 and IPASS3,4; INTEREST and IPASS were the two pivotal studies for the EU submission. IRESSA was first registered for NSCLC in 2002 but the significance of biomarkers and in particular EGFR mutations was discovered relatively late in its development. Early in development it was possible to show that there was complete inhibition of EGFR receptor signalling by the drug. Following the results from ISEL, a trial in a very refractory patient population, it became clear that it was not just necessary to inhibit the target but to find out if the growth of the tumour was truly dependent on the target. It should be noted that both ISEL and INTEREST were in an unselected patient population and were both initiated before the identification and biological significance of EGFR mutations was understood. FISH analysis was incorporated as a co-primary endpoint in the INTEREST trial to analyse EGFR-gene copy number. IPASS was the first and only trial in which patients were selected for treatment on the basis of clinical characteristics. It was designed shortly after the reporting of the ISEL results. Patient selection in the IPASS trial was based on clinical characteristics because, at the time, there was no clear candidate for a biomarker on which to recruit a large PhIII trial and the understanding of the significance of EGFR mutatio