Juan Oscar, Popat Sanjay
Department of Medical Oncology, University Hospital La Fe, Valencia, Spain.
Royal Marsden Hospital, London SW3 6JJ, UK.
Ther Adv Med Oncol. 2017 Mar;9(3):201-216. doi: 10.1177/1758834016687262. Epub 2017 Jan 30.
Discovery of sensitizing mutations in epidermal growth factor receptor ( and the subsequent development of EGFR tyrosine kinase inhibitors (TKIs) have substantially changed the treatment of lung cancer. First-line treatment with EGFR TKIs (gefitinib, erlotinib and afatinib) has demonstrated a superior response rate and progression-free survival (PFS) compared with chemotherapy in -mutation positive patients. However, a number of open questions remain, such as choice between the three EGFR TKIs licensed, treatment of patients unsuitable for chemotherapy due to morbidity or advanced age, management of acquired resistance and optimal biological sample to determine status. Recently the first head-to-head trial comparing gefitinib and afatinib (LUX-Lung 7) has been reported. Moreover, third-generation EGFR TKIs such as osimertinib, rociletinib, olmutinib and ASP8273, with preferential activity against T790M mutant tumours, the commonest resistance mechanism to EGFR TKIs, have shown promising results in early clinical trials, with osimertinib now licensed. In this review, we summarize latest advances in the treatment of -mutation positive patients focusing on controversial areas and emerging challenges to optimally treat these patients in the future.
表皮生长因子受体致敏突变的发现（以及随后表皮生长因子受体酪氨酸激酶抑制剂 （TKIs） 的研发）极大地改变了肺癌的治疗方式。在携带 突变的患者中，与化疗相比，表皮生长因子受体 TKIs（吉非替尼、厄洛替尼和阿法替尼）一线治疗已显示出更高的缓解率和无进展生存期（PFS）。然而，仍存在一些未解决的问题，例如三种获批的表皮生长因子受体 TKIs 之间的选择、因发病率或高龄而不适合化疗的患者的治疗、获得性耐药的管理以及确定 状态的最佳生物样本。最近，首个比较吉非替尼和阿法替尼的头对头试验（LUX-Lung 7）已有报道。此外，第三代表皮生长因子受体 TKIs，如奥希替尼、罗西替尼、奥美替尼和 ASP8273，对表皮生长因子受体 TKIs 最常见的耐药机制 T790M 突变肿瘤具有优先活性，在早期临床试验中已显示出有前景的结果，目前奥希替尼已获批。在本综述中，我们总结了携带 突变患者治疗的最新进展，重点关注有争议的领域以及未来优化这些患者治疗的新挑战。
