文档介绍：晚期非小细胞肺癌晚期非小细胞肺癌 EGFR-TKI EGFR-TKI 获得性耐药获得性耐药的热点研究及进展的热点研究及进展主要内容: ?? EGFR-TKI EGFR-TKI 作用机制、耐药机制作用机制、耐药机制??新药临床研究新药临床研究??前景展望前景展望 k k k EGFR P P ERBB3 P PP P AKT AKT KRAS Jak/Stat P P EGFR 信号传导的分子机制 J k k k EGFR P PP P P P TKI Gefitinib Erlotinib KRAS X Jak/Stat X AKT AKT X EGFR-TKI 作用机制主要内容: ?? EGFR-TKI EGFR-TKI 作用机制、耐药机制作用机制、耐药机制??新药研究新药研究??前景展望前景展望 EGFR-TKI 耐药机制 49% 5% 5% 3% 3% 2% 2% 11% 11% 23% 23% 2% 2% 3% 3% T790 k k k EGFR P P ERBB3 P PP P AKT AKT KRAS Jak/Stat P P T790 T790 Gefitinib Erlotinib T790M 介导 EGFR-TKI 耐药机制 EGFR-TKI 耐药热点研究梳理 EGFR EGFR -tki -tki 耐药耐药其他其他 T790 T790 突变突变 MET MET 扩增扩增 3 3 代代 TKI TKI 2 2 代代 TKI TKI MET MET 抑制剂抑制剂 Tivantini Tivantini b b onartuzmab onartuzmab Afatinib Afatinib itinib itinib CO1686/ CO1686/ AZD9291 AZD9291 RR10% RR10% PFS PFS 小于小于 4m 4m C01686 —— Rociletinib Rociletinib in Rociletinib in EGFR-Mutated Non EGFR-Mutated Non –– Small-Cell Small-Cell Lung Lung Cancer( Cancer( NCT01526928 NCT01526928 ) ) N=130 TKI AR NSCLC T790 突变情况 March 2012 and April 2014 N=130 突变阳性(46) 突变阴性(17) DCR 93% 59% RR 59% 29% PFS N Engl J Med 2015; 372:1700-1709 N Engl J Med 2015; 372:1700-1709 April 30, 2015 April 30, 2015 DOI: DOI: Best Response to Rociletinib: Best Response to Rociletinib: Each bar represents an individual patient, and the amplitude and direction of the bar represent the percent Each bar represents an individual patient, and the amplitude and direction of the bar represent the percent change in tumor burden during treatment pared with baseline. Tumor burden was measured as the sum of thel ongest diameters of the change in tumor burden during treatment pared 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 . The dashed line at 20% represents the boundary for tar