肺癌靶向治疗研究进展.ppt

晚期非小细胞肺癌EGFR-TKI获得性耐药 的热点研究及进展 主要内容： EGFR-TKI作用机制、耐药机制 新药临床研究 前景展望 k k k EGFR P P ERBB3 P P P P AKT KRAS Jak/Stat P EGFR信号传导的分子机制J k k k EGFR P P P TKI Gefitinib Erlotinib KRAS X Jak/Stat X AKT X EGFR-TKI作用机制 主要内容： EGFR-TKI作用机制、耐药机制 新药研究 前景展望EGFR-TKI耐药机制 49% 5% 3% 2% 11% 23% 2% 3% T790 k k k EGFR P ERBB3 P P AKT KRAS Jak/Stat P T790 Gefitinib Erlotinib T790M介导EGFR-TKI耐药机制 EGFR-TKI耐药热点研究梳理 EGFR-tki耐药 其他 T790突变 MET扩增 3代TKI 2代TKI MET抑制剂 Tivantinib onartuzmab Afatinib Dacomitinib CO1686/ AZD9291 RR10% PFS小于4m C01686——Rociletinib Rociletinib in EGFR-Mutated Non–Small-Cell Lung CancerNC N130 TKI AR NSCLCT790突变情况 March 2012 and April 2014N130 突变阳性46 突变阴性17 DCR 93%59% RR 59%29% PFS 13.1m 5.6m N Engl J Med 2015; 372:1700-1709April 30, 2015DOI: 10.1056/NEJMoa1413654 Best Response to Rociletinib:Each bar represents an individual patient, and the amplitude and direction of the bar represent the percent change in tumor burden during treatment as compared with baseline. Tumor burden was measured as the sum of thel ongest diameters of the target lesions, according to the Response Evaluation Criteria in Solid Tumors, version 1.1. The dashed line at 20% represents the boundary for determination of progressive disease, and the dashed line at ?30% represents the boundary for determination of partial response. FB denotes free base, and HBr hydrogen bromide salt. Rociletinib in EGFR-Mutated Non–Small-Cell Lung CancerNC N253 TKI AR NSCLC March 6,2013~August 1, 2014T790突变情况 N253 突变阳性138 突变阴性62 RR 61%（127） 21%（61） PFS 9.6m 2.8m N Engl J Med.?2015 Apr 30;37218:1689-99. doi: 10.1056/NEJMoa1411817. AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung CancerNCAZD9291 AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung CancerNCAZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung CancerNC. AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung CancerNC前景展望 3代TKI药物应用于耐药的晚期NSCLC患者前景良好。 Ⅰ ~ Ⅱ期临