Krebswissenschaft und -therapie

EGFR Primary T790M and L858R Double Mutation Confers Clinical Benefit to Erlotinib and Resistance to Osimertinib in One Lung Adenocarcinoma Patient: A Case Report

Abstract

Xiaoai Zhao, Lingxiao Zhang, Le Wang, Zheling Chen, Pan Li, Andi Zhao, Jin Yang, Hua Dong, Lin Shi, Dalei Wang, Xiaochen Zhao, Yizhou Ye, Fugen Li and Zheng Wang

Introduction: EGFR TKI has been widely studied in both research and clinic. However, only few limited studies focus on EGFR primary resistance rather than acquired mutation. Usually, EGFR T790M mutation is resistant to first generation TKI (erlotinib, gefitinib) and sensitive to third generation TKI Osimertinib. Here, we report an EGFR primary T790M and L858R double mutation patient confers clinical benefit to Erlotinib and resistance to Osimertinib.
Case presentation: Here we present a 70-year-old woman with lung adenocarcinoma harboredprimary T790M and L858R EGFR double mutation and underwent multiple lines of treatments. She benefited from the first-generation of EGFR TKI Erlotinib, and later quickly developed resistance to the third-generation TKI Osimertinib after disease progression, then followed a few rounds of chemotherapies. Multiple resistant EGFR mutations were detected, indicating frequent complex tumor heterogeneity in later stage patients caused by subclone evolution. Colonies with distinct Osimertinib resistance mutations included well known EGFR mutations L792V, L718V/R, G796S/A, and novel EGFR G729V and D1014V mutations, which are predicted to be acquired osimertinib resistance mutations by 3D-structural remodeling.
Conclusion: Our study revealed that EGFR primary T790M accompany with L858R mutation could benefit from erlotinib, and has stable disease for 7 months. The patient also benefited from chemotherapy for three months after resistance to osimertinib. ctDNA–based assay is a valuable tool for late stage cancer diagnosis, monitoring and intervention.