Third-generation EGFR-TKIs can be used to treat advanced non-small cell lung cancer patients with T790M resistance mutation induced by first- or second-generation EGFR-TKIs. However, it will also result in drug resistance, and the resistance mechanisms of third-generation EGFR-TKIs are complex. Here we reported a patient diagnosed with advanced lung adenocarcinoma and EGFR positive in September 2016. Following first-line targeted therapy with gefitinib, genetic testing showed EGFR T790M positive, which resulted in a change to osimertinib targeted therapy. In May 2021, troponin and creatinine levels were elevated, and the tumor hyperprogressed to severe lung cancer. Repeated genetic testing revealed that EGFR genotype converted to a non-classical mutation and EGFR T790M turned negative, which caused third-generation EGFR-TKI resistance. As a result, afatinib combined with anlotinib was selected to stabilize the patient's condition. We were inspired by the case that it reflects the significance and necessity of exploring the resistance mechanism and dynamically detecting genetic status throughout the course of treatment, which may help realize individualized precision therapy, and maximize the potential of patient.

中文翻译：

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阿法替尼联合安罗替尼成功治疗因 EGFR 基因型转换而导致的第三代 EGFR-TKI 耐药引起的严重肺癌。

第三代EGFR-TKI可用于治疗第一代或第二代EGFR-TKI诱导的T790M耐药突变的晚期非小细胞肺癌患者。但同时也会产生耐药性，且第三代EGFR-TKI的耐药机制较为复杂。在此，我们报道了一名2016年9月诊断为晚期肺腺癌且EGFR阳性的患者。一线靶向治疗吉非替尼后，基因检测显示EGFR T790M阳性，导致改用奥希替尼靶向治疗。2021年5月，肌钙蛋白和肌酐水平升高，肿瘤过度进展为严重肺癌。反复基因检测发现EGFR基因型转变为非经典突变，EGFR T790M转阴性，导致第三代EGFR-TKI耐药。因此，选择阿法替尼联合安罗替尼稳定患者病情。我们从这个案例中得到启发，它体现了探索耐药机制、在整个治疗过程中动态检测基因状态的意义和必要性，这可能有助于实现个体化精准治疗，最大限度地发挥患者的潜力。