Department of Oncology, Beijing Hospital, National Center of Gerontology, Beijing, China.
Department of In Vitro Diagnostic Testing, Beijing Institute of Medical Device Testing, Beijing, China.
Thorac Cancer. 2018 Dec;9(12):1774-1777. doi: 10.1111/1759-7714.12889. Epub 2018 Oct 8.
Acquired resistance inevitably occurs after initial treatment with first-generation EGFR-tyrosine kinase inhibitors (TKIs). Several mechanisms have been identified, including EGFR T790M mutation and HER2 amplification. Herein, we present the case of a patient who progressed on first-generation EGFR-TKIs and developed EGFR T790M mutation, HER2 amplification, and HER2 mutation. The administration of single-agent osimertinib yielded an inconsistent response, with worsened pleural effusion and a reduction to lung metastases, but remarkably, a partial response was achieved after four weeks of treatment with combined osimertinib and afatinib, with grade 1 rash and grade 2 diarrhea. Our findings indicate an overlap of T790M, HER2 amplification, and HER2 mutation, which is rarely reported. Moreover, HER2 mutation was identified during the development of resistance, suggesting that HER2 mutation may cause resistance to first-generation EGFR-TKIs.
获得性耐药不可避免地会在第一代 EGFR-酪氨酸激酶抑制剂（TKIs）初始治疗后发生。已经确定了几种机制，包括 EGFR T790M 突变和 HER2 扩增。在此，我们报告了一例在第一代 EGFR-TKIs 治疗后进展并发生 EGFR T790M 突变、HER2 扩增和 HER2 突变的患者。奥希替尼单药治疗的反应不一致，胸腔积液恶化，肺转移减少，但令人惊讶的是，奥希替尼联合阿法替尼治疗四周后，皮疹 1 级，腹泻 2 级，获得部分缓解。我们的发现表明 T790M、HER2 扩增和 HER2 突变存在重叠，这很少有报道。此外，在耐药性发展过程中发现了 HER2 突变，提示 HER2 突变可能导致对第一代 EGFR-TKIs 的耐药性。
