肺癌驱动基因的研究和EGFRTKI以外的靶向治疗研究进展(施春雷).pptVIP

ALK阳性NSCLC患者的预后更差 ALK 阳性 vs ALK 阴性 Yang P, et al. J Thorac Oncol. 2012;7: 90–97 Years since diagnosis PFS/RFS曲线 FISH(positive) versus FISH(negative) Years since diagnosis PFS/RFS曲线 IHC3(positive) versus IHC0/1 (negative) ALK 阳性 vs EGFR突变 vs NSCLC ALK阳性 EGFR突变 驱动基因 ALK融合基因 EGFR突变 临床病理特征 年轻、腺癌（粘液型）、不吸烟 东亚裔、腺癌（非粘液型）、不吸烟 患者预后 差 好 治疗方法 克唑替尼 EGFR-TKIs 中国ALK阳性非小细胞肺癌诊断专家共识 专家组推荐命名： 根据专家的讨论，从检测方法学角度考虑到ALK融合型肺癌不仅是基因序列层面的改变，ALK融合蛋白也是该类疾病中的重要变异，因此将此类疾病统称为ALK阳性非小细胞肺癌 中国ALK阳性非小细胞肺癌诊断专家共识 专家组推荐定义： ALK阳性非小细胞肺癌： 是指包括ALK FISH检测阳性、ALK序列融合变异或ALK融合蛋白表达阳性的肺癌，肿瘤细胞中存在ALK融合基因表达，是非小细胞肺癌的一个分子亚型，常见于腺癌，该类患者通常可从ALK抑制剂治疗中获益。 PROFILE 1007: Crizotinib vs Chemotherapy (2nd/3rd line therapy) Key entry criteria ALK+ by central FISH testing Stage IIIB/IV NSCLC 1 prior chemotherapy (platinum-based) ECOG PS 0?2 Measurable disease Treated brain metastases allowed N=318 Crizotinib 250 mg BID PO, 21-day cycle (n=159) Pemetrexed 500 mg/m2 or Docetaxel 75 mg/m2 IV, day 1, 21-day cycle (n=159) PROFILE 1007: NCEndpoints Primary PFS (RECIST 1.1, independent radiology review) Secondary ORR, DCR, DR OS Safety Patient reported outcomes (EORTC QLQ-C30, LC13) RANDOMIZE CROSSOVER TO CRIZOTINIB ON PROFILE 1005 aStratification factors: ECOG PS (0/1 vs 2), brain metastases (present/absent), and prior EGFR TKI (yes/no) a Shaw et al. ESMO 2012 aRECIST v1.1 ORRa by Independent Radiologic Review 65.3 19.5 ORR (%) ORR ratio: 3.4 (95% CI: 2.5 to 4.7); P0.001 Crizotinib (n=173) PEM/DOC (n=174) 80 60 40 20 0 Treatment 65.7 29.3 6.9 Crizotinib (n=172) PEM (n=99) DOC (n=72) Treatment 80 60 40 20 0 Shaw et al. ESMO 2012 Primary Endpoint: PFS by Independent Radiologic Review (ITT Population) Probability of survival without progression (%) 100 80 60 40 20 0 0 5 10 15 20 25 Time (months) 173 93 38 11 2 0 174 49 15 4 1 0 No. at risk Crizotinib PEM/DOC Crizotinib (n=173) PEM/DOC (n=174) Events, n (%) 100 (58) 127 (73) Median, mo 7.7 3.0 HR (95% CI) 0.49 (0.37 to 0.64) P 0.001 PEM/DOC, pemetrexed/do