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Acquired EGFR L718V Mutation as the Mechanism for Osimertinib Resistance in a T790M-Negative Non-Small-Cell Lung Cancer Patient

  • Zhe Yang
  • Jinqi Yang
  • Yedan Chen
  • Yang W. Shao
  • Xing WangEmail author
Therapy in Practice

Abstract

Background

The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has demonstrated significant clinical benefit in EGFR T790M-mutated non-small-cell lung cancer (NSCLC) patients, with extensive research focusing on the mechanisms of acquired resistance. However, there are limited studies on second-line treatment options for EGFR T790M-negative patients and their clinical outcomes.

Objective

We aimed to provide better understanding of the resistance mechanisms to osimertinib treatment as well as the therapeutic options for T790M-negative NSCLC patients.

Patients and methods

In this case study, a patient was admitted and diagnosed with stage IV lung adenocarcinoma. Tissue specimen and blood samples collected from baseline and during the course of treatment were subjected to genomic profiling of 416 cancer-related genes using hybridization capture-based targeted next-generation sequencing.

Results

Following progression on initial chemoradiotherapy, the patient received EGFR TKI treatment with icotinib upon the confirmation of carrying an EGFR L858R mutation. However, the patient was negative for the EGFR T790M mutation when he became resistant to icotinib. The patient received subsequent osimertinib treatment and achieved a progression-free survival (PFS) of 10.4 months. Upon disease progression, an acquired L718V mutation within the EGFR kinase domain was found, which may interfere with the binding of osimertinib to the kinase domain and confer resistance regardless of T790M status.

Conclusions

This is the first clinical evidence of EGFR L718V giving rise to osimertinib resistance in a T790M-negative context, which provides valuable information for the discovery of resistance mechanisms to osimertinib and guidance for personalized NSCLC treatment in such patients.

Notes

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this article.

Conflict of interest

Yedan Chen is an employee of Nanjing Geneseeq Technology Inc., China. Yang W. Shao is an employee of Nanjing Geneseeq Technology Inc., China, and Geneseeq Technology Inc., Canada. Zhe Yang, Jinqi Yang, and Xing Wang declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Zhe Yang
    • 1
  • Jinqi Yang
    • 2
  • Yedan Chen
    • 3
  • Yang W. Shao
    • 3
    • 4
    • 5
  • Xing Wang
    • 6
    Email author
  1. 1.Tumor Research and Therapy CenterShandong Provincial Hospital Affiliated to Shandong UniversityJinanChina
  2. 2.Medical Oncology DepartmentYanggu Xian People’s HospitalLiaochengChina
  3. 3.Medical DepartmentNanjing Geneseeq Technology IncNanjingChina
  4. 4.Translational Medicine Research InstituteGeneseeq Technology Inc.TorontoCanada
  5. 5.School of Public HealthNanjing Medical UniversityNanjingChina
  6. 6.Hospital OfficeShandong Provincial Hospital Affiliated to Shandong UniversityJinanChina

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