Takeda Masayuki, Nakagawa Kazuhiko
Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Curr Cancer Drug Targets. 2015;15(9):792-802. doi: 10.2174/156800961509151110143001.
Dysregulation of epidermal growth factor receptor (EGFR) signaling due to receptor overexpression or activating mutation is associated with cancer cell proliferation, metastasis, and survival. EGFR has become an important therapeutic target for non-small cell lung cancer (NSCLC), and several EGFR-targeted agents, such as tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs), have been developed. The EGFR-TKIs gefitinib, erlotinib, and afatinib have been approved for the treatment of advanced NSCLC, and sensitivity to these drugs has been shown to be associated with the presence of EGFR mutations. Various mAbs to EGFR have also been evaluated in preclinical and clinical studies. In particular, phase III trials have shown a clinically significant survival benefit for addition of the anti-EGFR mAbs cetuximab or necitumumab to a platinum doublet in chemotherapy-naïve patients with advanced NSCLC. We here summarize the results of completed and ongoing clinical trials of EGFR-targeted mAbs for the treatment of NSCLC.
由于受体过表达或激活突变导致的表皮生长因子受体(EGFR)信号失调与癌细胞增殖、转移和存活相关。EGFR已成为非小细胞肺癌(NSCLC)的重要治疗靶点,并且已经开发了几种EGFR靶向药物,如酪氨酸激酶抑制剂(TKIs)和单克隆抗体(mAbs)。EGFR-TKIs吉非替尼、厄洛替尼和阿法替尼已被批准用于治疗晚期NSCLC,并且已证明对这些药物的敏感性与EGFR突变的存在相关。各种针对EGFR的单克隆抗体也已在临床前和临床研究中进行了评估。特别是,III期试验表明,在初治的晚期NSCLC患者中,将抗EGFR单克隆抗体西妥昔单抗或奈昔妥单抗添加到铂类双联化疗中可带来具有临床意义的生存获益。我们在此总结了已完成和正在进行的针对NSCLC治疗的EGFR靶向单克隆抗体临床试验的结果。