Successful treatment of severe lung cancer caused by third-generation EGFR-TKI resistance due to EGFR genotype conversion with afatinib plus anlotinib

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.