Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain; Program of Solid Tumors, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
Medical Oncology Department, Gustave Roussy, France.
Crit Rev Oncol Hematol. 2020 Apr;148:102906. doi: 10.1016/j.critrevonc.2020.102906. Epub 2020 Feb 11.
Approximately 4% of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) present EGFR exon 20 in-frame insertions, accounting for 0.3 %-3.7 % of NSCLC. In addition, 2 %-4 % of patients with NSCLC harbor human epidermal growth factor receptor 2 gene (HER2) mutations, being the 90 % of them exon 20 insertions. These mutations confer intrinsic resistance to available EGFR tyrosine kinase inhibitors (TKIs) and anti-HER2 treatments, as they result in steric hindrance of the drug-binding pocket. Therefore, no targeted therapies have been approved for NSCLC patients with EGFR or HER2 exon 20- activating mutations to date and remain an unmet clinical need. Promising efforts to novel treatment development have been made. Early data provide encouraging activity of novel drugs targeting EGFR and HER2 mutations in metastatic NSCLC. In this review we will summarize all the data reported to date about these driver molecular alterations and potential targeted therapies.
大约 4%的表皮生长因子受体(EGFR)突变非小细胞肺癌(NSCLC)存在 EGFR 外显子 20 框架内插入，占 NSCLC 的 0.3%-3.7%。此外，2%-4%的 NSCLC 患者携带人类表皮生长因子受体 2 基因(HER2)突变，其中 90%为外显子 20 插入。这些突变导致对现有 EGFR 酪氨酸激酶抑制剂(TKIs)和抗 HER2 治疗的内在耐药，因为它们导致药物结合口袋的空间位阻。因此，迄今为止，尚无针对 EGFR 或 HER2 外显子 20 激活突变的 NSCLC 患者的靶向治疗药物获得批准，这仍然是一个未满足的临床需求。目前已经做出了有希望的新治疗方法的开发努力。早期数据提供了针对转移性 NSCLC 中 EGFR 和 HER2 突变的新型药物令人鼓舞的活性。在这篇综述中，我们将总结迄今为止关于这些驱动分子改变和潜在靶向治疗的所有数据。
