Osimertinib Did Not Respond to a Pulmonary Adenocarcinoma with Triple Mutations of Epidermal Growth Factor Receptor, G719S, T790M and S768I.

Uncommon epidermal growth factor receptor (EGFR) gene mutations include G719S, T790M and S768I. T790M gatekeeper mutation is the most frequent mechanism of acquired drug resistance to first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs). Osimertinib is a specific EGFR-TKI to overcome T790M resistance mutation. However, owing to a new drug and a rare mutation type, it remains unknown whether osimertinib is effective for acquired S768I. Herein, we reported a 76 year-old woman with pulmonary adenocarcinoma, which had acquired EGFR mutations of S768I and T790M in addition to original G719S after long gefitinib treatment. These mutations were detected in biopsy specimen of liver metastases. During two months of osimertinib, multiple liver metastases progressively enlarged. This case suggested that acquired S768I mutation might be resistant to osimeritinib, despite of co-occurrence of T790M.