School of Medicine, South China University of Technology, Guangzhou, China.
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Expert Opin Emerg Drugs. 2022 Jun;27(2):111-126. doi: 10.1080/14728214.2022.2063836. Epub 2022 Apr 14.
Epidermal growth factor receptor (EGFR) is one of the most common driver gene mutations in non-small-cell lung cancer (NSCLC). EGFR-tyrosine kinase inhibitors (TKIs) monotherapy and EGFR-TKI combined with chemotherapy or anti-angiogenesis drugs have significantly prolonged the survival of patients with EGFR-mutant NSCLC. However, disease progression caused by acquired resistance to EGFR-TKIs is inevitable. And patients with EGFR exon 20ins showed limited efficacy to EGFR-TKIs.
In this review, we initially evaluated the efficacy of existing treatments for EGFR-mutant NSCLC. Second, we reviewed the ongoing phase II and III clinical trials, provided the latest results, discussed the scientific rationale of these trials and the potential development issues.
The application of EGFR-TKIs has greatly changed the therapeutic strategies for advanced and resected NSCLC with EGFR mutations, and the 5-year overall survival (OS) rate for advanced NSCLC was close to 40%. The current research direction for the treatment of patients with EGFR mutations focuses on the following three aspects: uncommon EGFR mutation subtypes, brain metastases, and EGFR TKI-based combination therapy. Future studies on EGFR-mutant NSCLC therapy will focus on overcoming EGFR-TKI-related resistance, preventing drug resistance in advance, and developing bispecific antibody drugs.
表皮生长因子受体(EGFR)是非小细胞肺癌(NSCLC)中最常见的驱动基因之一。EGFR 酪氨酸激酶抑制剂(TKI)单药治疗和 EGFR-TKI 联合化疗或抗血管生成药物显著延长了 EGFR 突变 NSCLC 患者的生存时间。然而,由于获得性 EGFR-TKI 耐药,疾病进展是不可避免的。并且 EGFR 外显子 20ins 的患者对 EGFR-TKI 的疗效有限。
在这篇综述中,我们首先评估了现有治疗 EGFR 突变 NSCLC 的疗效。其次,我们回顾了正在进行的 II 期和 III 期临床试验,提供了最新结果,讨论了这些试验的科学原理和潜在的发展问题。
EGFR-TKI 的应用极大地改变了具有 EGFR 突变的晚期和可切除 NSCLC 的治疗策略,晚期 NSCLC 的 5 年总生存率(OS)接近 40%。目前治疗 EGFR 突变患者的研究方向集中在以下三个方面:罕见的 EGFR 突变亚型、脑转移和基于 EGFR TKI 的联合治疗。未来针对 EGFR 突变 NSCLC 的治疗研究将集中于克服 EGFR-TKI 相关耐药性、提前预防耐药性以及开发双特异性抗体药物。