Hamard Cécile, Ruppert Anne-Marie, Lavole Armelle, Rozensztajn Nathalie, Antoine Martine, Cadranel Jacques, Wislez Marie
GRC 04 UPMC, hôpital Tenon, Assistance Publique-hôpitaux de Paris, 4, rue de la Chine, 75970 Paris cedex 20, France.
GRC 04 UPMC, hôpital Tenon, Assistance Publique-hôpitaux de Paris, 4, rue de la Chine, 75970 Paris cedex 20, France; Service de pneumologie, hôpital Tenon, Assistance Publique-hôpitaux de Paris, 4, rue de la Chine, 75970 Paris cedex 20, France.
Ann Pathol. 2016 Jan;36(1):63-72. doi: 10.1016/j.annpat.2015.11.002. Epub 2016 Jan 6.
Recently, developments of therapies that target abnormally activated signaling pathways are increasing for patients with non-small cell lung cancer. EGFR mutations are found in about 10% of lung cancers, especially in adenocarcinoma, women and non-smokers. Three EGFR inhibitors (erlotinib, gefitinib and afatinib) received a European marketing authorization for up to first line treatment of EGFR mutated NSCLC. Effectiveness of EGFR inhibitors is higher than conventional chemotherapy. Third generation EGFR inhibitors (rociletinib, AZD9291) are effective for patients who develop a resistance mutation such as T790M resistance mutation; they obtained temporary authorization for use in France in 2015. The EML4-ALK translocation is found in about 5% of NSCLC and more particularly in adenocarcinoma of young non-smoking patients. Crizotinib is a new therapeutic standard in ALK translocated NSCLC in second line. Ceritinib is a 2nd generation ALK inhibitor which received a European marketing authorization for up to treatment of ALK translocated NSCLC after progression with crizotinib. INCA supports ACSé program evaluating the efficacy of crizotinib in NSCLC amplified for MET or translocated for ROS1 and ACSé program evaluating the efficacy of vemurafenib in tumors non melanoma mutated V600E BRAF. The role of other biomarkers such as KRAS, BRAF, HER2 and PI3KCA mutations remains to be defined in NSCLC.
最近，针对非小细胞肺癌患者的、靶向异常激活信号通路的治疗方法不断涌现。约10%的肺癌中可发现EGFR突变，尤其是在腺癌、女性和非吸烟者中。三种EGFR抑制剂（厄洛替尼、吉非替尼和阿法替尼）已获得欧洲上市许可，用于EGFR突变的非小细胞肺癌的一线治疗。EGFR抑制剂的疗效高于传统化疗。第三代EGFR抑制剂（罗西替尼、AZD9291）对发生T790M耐药突变等耐药突变的患者有效；它们于2015年在法国获得临时使用许可。约5%的非小细胞肺癌中可发现EML4-ALK易位，尤其在年轻非吸烟患者的腺癌中。克唑替尼是ALK易位的非小细胞肺癌二线治疗的新的治疗标准。色瑞替尼是第二代ALK抑制剂，已获得欧洲上市许可，用于克唑替尼治疗后进展的ALK易位的非小细胞肺癌的治疗。INCA支持评估克唑替尼在MET扩增或ROS1易位的非小细胞肺癌中的疗效的ACSé项目，以及评估维莫非尼在V600E BRAF突变的非黑色素瘤肿瘤中的疗效的ACSé项目。其他生物标志物如KRAS、BRAF、HER2和PI3KCA突变在非小细胞肺癌中的作用仍有待确定。
