慢性晚期NSCLC的新机遇与新挑战.ppt

2014 ASCO指南，EGFR与ALK“RECIST首次进展后”均需持续治疗 Gerber DE,?et al. Am Soc Clin Oncol Educ Book.?2014:e353-65.? 进展，如何评估？ ? PD ? non-PD PD or non-PD ??? 大样本回顾性研究: 一线EGFR突变患者RECIST进展后，持续EGFR-TKIs治疗OS获益 组别 定义 中位OS(自开始EGFR-TKIs治疗) Group A(n=148) RECIST PD + Clinical PD,TKI stopped 16.7 Group B(n=154) RECIST PD without Clinical PD,TKI stopped 24.4 Group C(n=84) RECIST PD without Clinical PD, TKI continued 28.6 Group D(n=64) TKI stopped due to other reasons 15.9 Presented By Yukio Hosomi at 2014 ASCO Annual Meeting 肿瘤的生物学特征：高度异质性 EGFR突变：38%存在异质性 ALK WT ALK Fusion ALK Fusion ALK融合：≈100%存在异质性 1.Marusyk A,et al.Nat Rev?Cancer.?2012 Apr 19;12(5):323-34. 2.Bai H,et al. J Clin Oncol.?2012 Sep 1;30(25):3077-83. 肿瘤异质性是靶向药物耐药的主要原因之一 EGFR 旁路激活占20%； ALK其他通路激活占30%-50%1 肿瘤异质性导致耐药模式2 1.Camidge DR,et al. Nat Rev Clin Oncol.?2014 Jul 1. 2. Meacham CE,et al. Nature.?2013 Sep 19;501(7467):328-37. Lung Cancers with Concomitant EGFR Mutations and ALK Rearrangements Yang JJ, Zhang XC, Wu YL et al. CCR 2014 双突变患者生存期最短 Kris MG,et al. JAMA.?2014 May 21;311(19):1998-2006. 病树前头万木春 多种有效药物的合理安排 靶向治疗的评估体系 肿瘤异质性 By Lisa Hutchinson Chief Editor of Nature Reviews Clinical Oncology Hutchinson L,et al. Nat Rev Clin Oncol.?2014 Feb;11(2):61-2. “So, if we are to beat cancer, we have to think like cancer” Alectinib 敏感 Alectinib 敏感 1.Friboulet L,et al. Cancer?Discov.?2014 Jun;4(6):662-73. 2. Kodama T,et al. Cancer Lett.?2014 Jun 2. pii: S0304-3835(14)00304-8.? ALK’s Next Move: “三次”突变 克唑替尼与Ceritinib经治的患者Alectinib仍有效 总结 * * * * 4. Differential sensitivities to EGFK-TKIs and crizotinib for the 3 patterns of protein coexpression of mutantEGFRand rearranged ALK. H-H, H-L, and L-H indicate high p-EGFR and high p-ALK, high p-EGFR and low p-ALK, and low p-EGFR and high p-ALK, respectively. In the H-H and H-L panels, most patients showed responsiveness to first-line EGFR-TKI treatment, as this representative case did (A–D, P6 and E–H, P8). In the L-H panel, 2 patients showed PRs to second- or third-line crizotin