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Generations of epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR -TKIs) can significantly improve the outcome of EGFR -positive NSCLC patients. However, acquired TKIs-resistant mutations are inevitable. Except the common EGFR alterations, more and more rare mutations are revealed by next-generation sequencing (NGS), the clinical significance of which are still unclear. Here, we report an advanced lung adenocarcinoma patient who harbored two novel EGFR exon 19 deletions (750_758del and I759S) at the beginning and exhibited a short response to icotinib for 7.0 months. Then, secondary resistance EGFR T751_I759delinsS occurred. Chemotherapy combined with bevacizumab and erlotinib was administered in turn but failed. Standard-dose osimertinib (80 mg daily) obtained durable clinical remission for 16 months, and high-dose osimertinib (160 mg daily) further prolonged the survival of 9 months after leptomeningeal metastases (LM) occurring. This study presented the first case of intractable terminal NSCLC in a patient with EGFR 750_758del, I759S and T751_I759delinsS mutations, who responded positively to osimertinib and achieved a prolonged OS of 52 months, providing a potential therapeutic option for the patients harboring these particular EGFR mutations.

oncotargets and therapy

&lt;p&gt;Three Novel &lt;em&gt;EGFR&lt;/em&gt; Mutations (750_758del, I759S, T751_I759delinsS) in One Patient with Metastatic Non-Small Cell Lung Cancer Responding to Osimertinib: A Case Report&lt;/p&gt;