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

• Main Authors: Zhang Y, He B, Zhou D, Li M, Hu C
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-12-01
• Series: OncoTargets and Therapy
• Subjects: NSCLC; EGFR; AZD9291; T790M; G724S; resistance
• Online Access: https://www.dovepress.com/newly-emergent-acquired-egfr-exon-18-g724s-mutation-after-resistance-o-peer-reviewed-article-OTT

Yan Zhang,1 Bixiu He,2 Dongbo Zhou,2 Min Li,1 Chengping Hu1 1Department of Respiratory Medicine, Xiangya Hospital (Key Cite of National Clinical Research Center for Respiratory Disease), Central South University, Changsha, Hunan, P.R. China; 2Department of Gerontology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China 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. Keywords: NSCLC, EGFR mutation, tyrosine kinase inhibitor, next-generation sequencing