Significant Benefits of Osimertinib Against Adenosquamous Carcinoma Harboring Germline T790M Mutation

Background The identification of epidermal growth factor receptor (EGFR) mutations represents a milestone in the treatment of advanced non-small cell lung cancer. Patients with lung adenosquamous carcinomas (ASCs) rarely present with germline EGFR T790M mutation. The optimal treatment for cancers with germline EGFR T790M mutation (especially ASC) is not clear. Materials and Methods Using next-generation sequencing, we tested 450 cancer-related genes in a 27-year-old patient's lung adenosquamous carcinoma and matched blood samples. Germline mutations in samples from the patient's available relatives were identified by Sanger sequencing. Results We identified germline EGFR T790M mutation in the patient's lung adenosquamous carcinoma. He was treated with osimertinib and achieved complete response for more than 30 months, without significant drug-related adverse events. Genetic testing showed that germline EGFR T790M mutation might be a characteristic of inherited lung cancer. Conclusion Osimertinib can be a treatment option for patients with lung ASC harboring germline EGFR T790M mutation. Key Points A patient with adenosquamous carcinoma harboring a germline T790M mutation responded well to osimertinib with a progression-free survival of more than 30 months and without any unexpected toxicities. Osimertinib is effective for patients with lung squamous cell carcinoma with T790M and L858R mutations. The germline EGFR T790M mutation is associated with genetic susceptibility to lung cancer. The clinical use of next-generation sequencing could maximize the benefits of precision medicine in patients with cancer.