肺癌精准治疗新进展.ppt

肺癌从单病种——组织分型——分子分型 * * AUC, area under the curve; Cmax, maximum concentration; CSF, cerebrospinal fluid; LOQ, limit of quantitation; NV, no value determined (compound detected at only 1 or 2 time points). *50 mg/kg, Kp average of brain/plasma from 3 available time points, AUC couldnot be determined ?5 mg/kg study ?No compound detected in the brain. Kp value determined from brain LOQ and plasma Cmax, CSF Kpuu average of 3 timepoints a3rd generation irreversible bAZD9291 metabolite c1st generation reversible Talking Points In rat models, osimertinib was the only EGFR-TKI tested with significant brain permeability1 Macaque PET images indicate osimertinib was the only compound to achieve significant brain penetrance after microdoses of EGFR-TKIs1 Reference Colclough N, Ballard P, Barton P, et al. Preclinical comparison of the blood brain barrier (BBB) permeability of osimertinib with other EGFR TKIs [abstract and poster]. Poster presented at: 28th European Organisation for Research and Treatment of Cancer, the National Cancer Institute, and the American Association for Cancer Research Molecular Targets and Cancer Therapeutics Symposium; 29 November 2016; Munich, Germany. Eur J Cancer. 2016:69(S28). Abs 64. * Colclough 2016 col3 Figure and Table2 Colclough 2016 col2 bullet 3 Colclough 2016 col2 bullet 4, Figure 1 footnotes. Updated slide * 肺癌精准治疗新进展 Li T, et al. J Clin Oncol. 2013 Mar 10;31(8):1039-49. ? ALK ? HER2 ? BRAF ? PIK3CA ? AKT1 ? MAP2K1 ? NRAS ? ROS1 ? RET ? KRAS ? EGFR ? Unknown ? FGFR1 Amp ? EGFRvlll ? PI3KCA ? EGFR ? DDR2 ? Unknown Squamous cell carcinoma* Adenocarcinoma* NSCLCas one disease Histology-based subtyping Molecular-based subtyping 分水岭 2001 2004 2005 2017 2008 非选择人群以OS为终点 临床试验：巨大人群， 靶向治疗获益不明显 IDEAL121-2 ISEL3 BR214 INTEREST5 INTACT126-7 TALENT8 TRIBUTE9 SATURN10 IPASS 全球首个 优势人群 靶向治疗 研究11 以突变选择人群以PFS为 终点, 临床试验：相对较小的 人群，靶向治疗获益明显 NEJ00212 WJOG340513 OPTIMAL14 EURTAC15 ENSURE16 LUX-Lung317 Lux-Lung618 CONVINCE19 未来 1. Fukuoka M, et al. J