Sun Jong-Mu, Lee Se-Hoon, Ahn Jin Seok, Park Keunchil, Ahn Myung-Ju
a Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.
Expert Opin Pharmacother. 2017 Feb;18(2):225-231. doi: 10.1080/14656566.2017.1285283.
The T790 M mutation of the epidermal growth factor receptor (EGFR) gene is the most common mechanism underlying resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR TKI, shows robust clinical efficacy in patients with T790 M-mutated lung cancer. Areas covered: We analyzed and reviewed clinical data for which patients who experienced acquired resistance to first- or second-generation EGFR TKIs. In addition, we briefly reviewed the potential role of osimertinib as a first-line therapy. Expert opinion: Osimertinib was recently licensed for use in NSCLC patients with acquired resistance to other EGFR TKIs due to a T790 M mutation. However, unresolved issues surrounding the optimal application of osimertinib remain, specifically the development of a plasma-based mutation test to overcome the difficulty of repeat biopsy, the efficacy of osimertinib for brain or leptomeningeal metastases, the development of resistance to osimertinib, and the use of osimertinib therapy as a first-line treatment. Many ongoing studies are currently exploring these issues.
表皮生长因子受体（EGFR）基因的T790M突变是非小细胞肺癌（NSCLC）患者对第一代或第二代EGFR酪氨酸激酶抑制剂（TKIs）耐药的最常见机制。奥希替尼作为第三代EGFR TKI，在T790M突变的肺癌患者中显示出强大的临床疗效。涵盖领域：我们分析并回顾了对第一代或第二代EGFR TKIs产生获得性耐药的患者的临床数据。此外，我们简要回顾了奥希替尼作为一线治疗的潜在作用。专家观点：奥希替尼最近被批准用于因T790M突变而对其他EGFR TKIs产生获得性耐药的NSCLC患者。然而，围绕奥希替尼最佳应用的未解决问题仍然存在，特别是开发基于血浆的突变检测以克服重复活检的困难、奥希替尼对脑转移或软脑膜转移的疗效、对奥希替尼的耐药性发展以及将奥希替尼治疗用作一线治疗。目前许多正在进行的研究正在探索这些问题。
