Exceptional response to afatinib in a patient with persistent G719A EGFR-mutant NSCLC

We present a patient with metastatic NSCLC harboring a compound EGFR mutation with co-occurring G719A and T790M mutation. T790M mutation was treatment emergent mutation when patient was on early generation tyrosine kinase inhibitors. Initial Guardant 360 showed that G719A was the dominant clone. Following, osimertinib, the patient had only a radiographic disease stabilization and then developed both clinical and radiographic progression. On progression, T790M was undetectable but G719A continued to be the dominant clone. Subsequent administration of afatinib led to a clinical and radiological response. To our knowledge, this is the first case report describing co-occurrence of EGFR G719A and T790M mutations and the clonal evolution during treatment with anti-EGFR therapies.