非小细胞肺癌治疗展望（调研报告）.pptVIP

* * * * * * * The addition of TG4010 to fi rst-line chemotherapy for NSCLC is feasible. Several efficacy metrics show a better outcome when the cancer vaccine is added, supporting the hypothesis of synergy between immunotherapy and chemotherapy. Outcome is particularly improved by the addition of TG4010 when the following biomarkers are normal at baseline: triple-positive CD16+CD56+CD69+ lymphocytes, plasma content in soluble CD54, macrophage colony stimulating factor, and interleukin 6. This suggests that the expected therapeutic effect of TG4010 is conditioned by the patient’s immune or inflammatory status (or both). This hypothesis might apply to other cancer vaccines and immunotherapy products and should therefore be tested in their development. * 只有靶向治疗需要进行基因水平的选择吗？ 虽然我们对于NSCLC很多驱动基因已知，但是没有驱动基因突变的病人还是很多的，他们该如何治疗？ 传统的不经选择的化疗方法疗效局限，且大多数人是在陪靶化疗，没有得到获益，但是还要承受化疗的严重毒副反应。 不同的化疗药物有它特定的优势人群吗？ 虽然我们通过临床特征和病理特征进行选择以后得到了改善。但是并不喜人，化疗也可以通过基因来更加明确的选择吗？ Predictive Tests for First Line/ Maintenance Chemotherapy Platinum Drugs ERCC1 Gemcitabine RRM1 ALIMTA TS (thymidylate synthase) IALT-Bio: ERCC1 Adjuvant Cisplatin-Based Chemotherapy ERCC1 Negative = benefited from cisplatin chemotherapy compared to observation (HR = 0.65) (p 0.002) ERCC1 Positive = no benefit from cisplatin chemotherapy compared to observation (HR = 1.14) (p = 0.40) Olaussen, NEJM 355:983, 2006 临床上如何应用ERCC1 的数据？ 分期、年龄、并发症在治疗方案的选择中起到关键的决定作用。 在年轻的、体力状态评分好的病人中，可以不考虑ERCC1的表达情况，适用铂类治疗。 ERCC1 的表达在那些风险效益比不明朗的患者，例如：老年患者、有并发症的患者以及1B期的患者的治疗策略的选择中起着主要的作用。 R A N D O M I Z E A S S I G N M E N T 1 : 2 Low ERCC1 mRNA (docetaxel and cisplatin) Experimental arm (ERCC1 mRNA level) Control arm (docetaxel and cisplatin) High ERCC1 mRNA (docetaxel and gemcitabine) Primary endpoint: response rate Genotypic International Lung Trial (GILT) Customizing Chemotherapy by ERCC1 mRNA Profiling in Advanced NSCLC Cobo M et al. J Clin Oncol 2007 Outcome Control (n = 141) Genotypic Group (n = 225) Low Genotypic Group (n = 129) Hig