Ralki Mike, Maes Brigitte, Pat Karin, Wynants Jokke, Cuppens Kristof
Department of Pulmonology and Thoracic Oncology, Jessa Hospital, Hasselt, Belgium.
Department of Pathology and Molecular Biology, Jessa Hospital, Hasselt, Belgium.
Case Rep Oncol. 2019 Aug 6;12(2):625-630. doi: 10.1159/000502214. eCollection 2019 May-Aug.
Epidermal growth factor receptor (EGFR)-targeted therapy has become standard of care in advanced stages EGFR-mutant non-small cell lung cancer. Acquired resistance to first-line EGFR-tyrosine kinase inhibitor (TKI) and subsequent disease progression is a common problem and mostly due to a secondary mutation (T790M) in EGFR. We report a case of a patient with EGFR-mutated lung adenocarcinoma who developed a complex resistance profile: T790M mutation, HER2 mutation and HER2 amplification after first-line EGFR-TKI. This patient was safely treated with a combination of osimertinib and trastuzumab and achieved a clinically meaningful and clear molecular response. This is the first reported case of acquired resistance to first-line EGFR-TKI based on three resistance mechanisms, treated with molecular targeted combination therapy.
表皮生长因子受体（EGFR）靶向治疗已成为晚期EGFR突变型非小细胞肺癌的标准治疗方法。对一线EGFR酪氨酸激酶抑制剂（TKI）产生获得性耐药及随后的疾病进展是一个常见问题，主要是由于EGFR中的继发性突变（T790M）。我们报告了1例EGFR突变型肺腺癌患者，该患者在一线EGFR-TKI治疗后出现了复杂的耐药情况：T790M突变、HER2突变和HER2扩增。该患者接受奥希替尼和曲妥珠单抗联合治疗，安全有效，并实现了具有临床意义且明确的分子反应。这是首例报道的基于三种耐药机制对一线EGFR-TKI产生获得性耐药并接受分子靶向联合治疗的病例。
