Newly emergent acquired EGFR exon 18 G724S mutation after resistance of a T790M specific EGFR inhibitor osimertinib in non-small-cell lung cancer: a case report

Abstract

BACKGROUND: T790M mutation is well known as the most common mechanism for resistance to the first- and second-generation tyrosine kinase inhibitors (TKIs) for EGFR mutation in non-small-cell lung cancer. Several third-generation EGFR TKIs, such as osimertinib, have been explored and approved for conquering this resistance; however, acquired resistance to osimertinib is evident and the resistance mechanisms remain complex and incompletely explored. CASE PRESENTATION: A non-smoking 58-year-old female patient was initially diagnosed with lung adenocarcinoma harboring EGFR exon 19 deletion and clinically responded to initial gefitinib treatment. The patient progressed on gefitinib after >1 year and a T790M mutation was detected in tissue biopsy by next-generation sequencing (NGS). Osimertinib treatment was administrated for several months and an acquired rare EGFR G724S mutation was detected via NGS blood sample after osimertinib resistance. CONCLUSION: The specific mechanisms of acquiring drug resistance for EGFR-TKIs have not been fully explored. EGFR G724S mutation might be associated with osimertinib resistance but more studies about the mechanism should be explored.