Department of Medical Oncology, Santa Maria della Misericordia Hospital, University of Perugia, Piazzale L. Severi n. 1, 06132 Perugia, Italy.
Department of Medical Oncology, Santa Maria della Misericordia Hospital, University of Perugia, Piazzale Menghini, Perugia, Italy.
Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618808659. doi: 10.1177/1753466618808659.
Epidermal growth factor receptor ( EGFR) gene mutations identify a molecularly defined subset of non-small cell lung cancer (NSCLC) patients who display an excellent sensitivity to EGFR tyrosine kinase inhibitors (TKIs). First-generation reversible EGFR TKIs, gefitinib and erlotinib have been proven to improve the objective response rate and to prolong the progression-free survival compared with standard chemotherapy in large phase III trials. Unfortunately, virtually all patients develop resistance to treatment, usually within 9-12 months. Afatinib is an irreversible ErbB family inhibitor initially designed to overcome the development of resistance. Compared with gefitinib in a first-line setting, afatinib prolonged progression-free survival and time to treatment failure, without impacting on overall survival in the general population of EGFR-mutant patients. However, afatinib has been shown to prolong overall survival in the subset of patients with an EGFR exon 19 deletion compared with chemotherapy. The aim of this review is to summarize the clinical evidence available to date and to critically discuss the place in therapy of afatinib in the rapidly expanding landscape of EGFR-mutant NSCLC first-line therapy.
表皮生长因子受体 (EGFR) 基因突变鉴定出非小细胞肺癌 (NSCLC) 患者的一个分子定义亚组，这些患者对 EGFR 酪氨酸激酶抑制剂 (TKI) 显示出极好的敏感性。第一代可逆 EGFR TKI，吉非替尼和厄洛替尼已被证明在大型 III 期试验中与标准化疗相比提高了客观缓解率并延长了无进展生存期。不幸的是，几乎所有患者都对治疗产生了耐药性，通常在 9-12 个月内。阿法替尼是一种最初设计用于克服耐药性的不可逆 ErbB 家族抑制剂。与一线治疗中的吉非替尼相比，阿法替尼延长了无进展生存期和治疗失败时间，而不会影响 EGFR 突变患者的总体生存期。然而，阿法替尼已被证明在 EGFR 外显子 19 缺失的患者亚组中与化疗相比可延长总生存期。本综述的目的是总结迄今为止可用的临床证据，并批判性地讨论阿法替尼在快速发展的 EGFR 突变 NSCLC 一线治疗领域中的治疗地位。
