非小细胞肺癌治疗展望课件.pptVIP

厦门, CSCO 2009 非小细胞肺癌治疗展望 吴一龙 广东省肺癌研究所 广东省人民医院 广东省医学科学院 Tarceva六周年庆/济南 Therapeutic Advances in the Last 5-10 Years Biomarker-driven therapy for EGFR-mutant ALK-positive NSCLC and targeted therapy (EGFR TKIs Crizotinib) No major advances NSCLC (Advanced Stage) SCLC (Limited Extensive) Unmet Needs to Advance Personalized Therapy in NSCLC Recognition of lung cancer complexity at the genomic level -including inter- and intra patient tumor heterogeneity Integration of this genomic complexity into clinical decision-making process NSCLC (Early Stage) No major advances Future Patient B versus Patient A Patient A Homogeneous Patient A Heterogeneous Patient A Evolution Patient A Patient B versus Traditional View Inter-patient Tumor Heterogeneity Models for Inter- and Intra-Patient Tumor Heterogeneity Intra-patient Tumor Heterogeneity Evolution over time with therapy or EGFR MT+ ALK+ EGFR MT+ EGFR MT- Resistance Mutation T790M Evolutionary Biology Tumor Resistance Intra-tumor heterogeneity is present at baseline Reducing sensitive clones by therapy permits unopposed growth of less fit resistant clones or emergence of a new clone (“Tumor Darwinism”) Separating new “drivers” from emergent “passengers” is becoming increasingly complex Evolution over time with therapy “Driver” Oncogene New “Driver” Evolution over time with therapy “Driver” Oncogene New “Driver” Scenario 1 Scenario 2 from Gandara et al: Clin Lung Cancer, 2012 血液分子标志物研究: 更好的全貌，更容易的方法？ Detection of EGFR activating mutations from plasma DNA as a potent predictor of survival outcomes in FASTACT 2 study: A randomized phase III study on intercalated combination of erlotinib (E) and chemotherapy (C) Mok T, Wu YL et al ASCO 2013 - EGFR 突变状态对治疗选择的影响 A phase II trial comparing pemetrexed with gefitinib as the second-line treatment of non-squamous NSCLC patients with wild-type EGFR (CTONG0806) N ＝157 Primary endpoi