Morin-Ben Abdallah Sami, Hirsh Vera
Department of Oncology, McGill University Health Centre, Montreal, QC, Canada.
Front Oncol. 2017 May 16;7:97. doi: 10.3389/fonc.2017.00097. eCollection 2017.
Somatic epidermal growth factor receptor (EGFR) mutations are present in around 50% of Asian patients and in 10-15% of Caucasian patients with metastatic non-small cell lung cancer (NSCLC) of adenocarcinoma histology. The first-generation EGFR-tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib have demonstrated improved progression-free survival (PFS) and response rates but not overall survival (OS) benefit in randomized phase III trials when compared with platinum-doublet chemotherapy. All patients treated with EGFR-TKIs will eventually develop acquired resistance to these agents. Afatinib, an irreversible ErbB family blocker, has shown in two randomly controlled trials in patients with EGFR-activating mutations, a significant improvement in PFS and health-related quality of life when compared to platinum-based chemotherapy. Afatinib improved OS in patients with Del19 mutations. In patients having progressed on first-generation EGFR-TKIs, afatinib did lead to a clinical benefit. A randomly controlled trial showed that PFS was significantly superior with afatinib vs. erlotinib in patients with squamous NSCLC in the second-line setting. A phase IIb trial comparing afatinib and gefitinib in first-line EGFR positive NSCLC showed significantly improved PFS with afatinib but OS was not significantly improved.
在组织学类型为腺癌的转移性非小细胞肺癌（NSCLC）患者中，约50%的亚洲患者及10%-15%的白种患者存在体细胞表皮生长因子受体（EGFR）突变。与铂类双联化疗相比，第一代EGFR酪氨酸激酶抑制剂（TKIs）吉非替尼和厄洛替尼在随机III期试验中显示出无进展生存期（PFS）和缓解率有所改善，但总生存期（OS）并无获益。所有接受EGFR-TKIs治疗的患者最终都会对这些药物产生获得性耐药。阿法替尼是一种不可逆的ErbB家族阻滞剂，在两项针对EGFR激活突变患者的随机对照试验中，与铂类化疗相比，其PFS和健康相关生活质量有显著改善。阿法替尼改善了Del19突变患者的OS。在第一代EGFR-TKIs治疗后病情进展的患者中，阿法替尼确实带来了临床获益。一项随机对照试验表明，在二线治疗中，阿法替尼治疗鳞状NSCLC患者的PFS显著优于厄洛替尼。一项IIb期试验比较了阿法替尼和吉非替尼用于一线EGFR阳性NSCLC的疗效，结果显示阿法替尼的PFS显著改善，但OS未显著改善。
