Köhler Jens, Schuler Martin
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Germany.
Onkologie. 2013;36(9):510-8. doi: 10.1159/000354627. Epub 2013 Aug 19.
Non-small cell lung cancer (NSCLC) consists of several histomorphologically defined phenotypes that display an enormous genetic variability. In recent years, epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma has emerged as a unique subset of NSCLC in terms of etiopathogenesis and tumor biology. Since the introduction of the reversible EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib, patients with metastatic EGFR mutation-positive lung cancer can be offered a therapeutic alternative that has proven its superiority over standard platinum-based chemotherapy. However, primary or acquired resistance limits the therapeutic success of these targeted agents. Irreversible inhibitors targeting all ErbB family receptor tyrosine kinases, such as afatinib and dacomitinib, have been developed to confer sustained disease control in ErbB-dependent cancers. The large LUX-Lung 3 phase III trial recently reported afatinib to be clearly superior over the most effective platinum doublet in patients with EGFR mutation-positive lung cancer. To fully exploit the clinical activity of afatinib, proactive management of its gastrointestinal and dermatologic toxicities is advised.
非小细胞肺癌（NSCLC）由几种组织形态学定义的表型组成，这些表型显示出巨大的基因变异性。近年来，表皮生长因子受体（EGFR）突变阳性的肺腺癌在病因发病机制和肿瘤生物学方面已成为NSCLC的一个独特亚组。自从可逆性EGFR酪氨酸激酶抑制剂（TKIs）厄洛替尼和吉非替尼问世以来，转移性EGFR突变阳性肺癌患者可以获得一种已被证明比标准铂类化疗更具优势的治疗选择。然而，原发性或获得性耐药限制了这些靶向药物的治疗效果。已开发出靶向所有ErbB家族受体酪氨酸激酶的不可逆抑制剂，如阿法替尼和达可替尼，以在ErbB依赖性癌症中实现持续的疾病控制。大型III期LUX-Lung 3试验最近报告，在EGFR突变阳性肺癌患者中，阿法替尼明显优于最有效的铂类双联化疗方案。为了充分发挥阿法替尼的临床活性，建议对其胃肠道和皮肤毒性进行积极管理。
