Department of Respiratory and Critical Care Medicine, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University , Nanjing, 210002, China.
The State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, 210002, China.
Invest New Drugs. 2021 Oct;39(5):1419-1421. doi: 10.1007/s10637-021-01108-3. Epub 2021 Apr 9.
Compound epidermal growth factor receptor (EGFR) mutations are defined as double or multiple independent mutations of the EGFR tyrosine kinase domain (TKD), in which an EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutation is identified together with a mutation of unclarified clinical significance. Lung adenocarcinoma with compound EGFR mutation shows poor clinical response to EGFR-TKIs. Kobayashi et al. reported a non-small-cell lung cancer (NSCLC) patient whose tumor had EGFR exon21 L858R/A871G mutation presented rapid disease progression to erlotinib. However, in this case, we present an EGFR exon21 L858R/A871G mutation patient exerted significant benefit to icotinib, another first-generation EGFR-TKI, indicating that different EGFR-TKIs have diversiform sensitive sites and therapeutic effects, consistent mutation sites might achieve heterogeneous benefits from different EGFR-TKIs. Our case report provides promising EGFR-TKI for clinical treatment with EGFR exon21 L858R/A871G mutation in NSCLC. More dedicated efforts are needed to clarify their biologic effects on disease course and drug responsiveness.
复合表皮生长因子受体(EGFR)突变被定义为 EGFR 酪氨酸激酶结构域(TKD)的双重或多重独立突变,其中鉴定出 EGFR-酪氨酸激酶抑制剂(TKI)敏感突变,同时存在不明临床意义的突变。具有复合 EGFR 突变的肺腺癌对 EGFR-TKIs 的临床反应较差。小林等人报道了一名非小细胞肺癌(NSCLC)患者,其肿瘤具有 EGFR 外显子 21 L858R/A871G 突变,对厄洛替尼迅速出现疾病进展。然而,在这种情况下,我们报告了一名 EGFR 外显子 21 L858R/A871G 突变患者对另一种第一代 EGFR-TKI 伊可替尼表现出显著获益,表明不同的 EGFR-TKIs 具有不同的敏感部位和治疗效果,相同的突变位点可能从不同的 EGFR-TKIs 中获得不同的获益。我们的病例报告为 NSCLC 中具有 EGFR 外显子 21 L858R/A871G 突变的患者提供了有前途的 EGFR-TKI 治疗选择。需要进一步努力阐明它们对疾病进程和药物反应性的生物学影响。