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Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer

  • J. Gao
  • H.-R. Li
  • C. Jin
  • J.-H. Jiang
  • J.-Y. DingEmail author
Review Article
  • 151 Downloads

Abstract

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC. The mechanisms of acquired resistance can be classified as three types: target gene mutation, bypass signaling pathway activation and histological transformation. And the most common mechanism is T790M which accounts for approximately 50% of all subtypes. Many strategies have been explored to overcome the acquired resistance to EGFR TKI. Continuation of EGFR TKI beyond progressive disease is confined to patients in asymptomatic stage when the EGFR addiction is still preserved in some subclones. While the combination of EGFR TKI and chemotherapy or other targeted agents has improved the survival benefit in EGFR TKI resistant patients, there are controversies within them. The next-generation EGFR TKI and immunotherapy represent two novel directions for overcoming acquired resistance and have achieved promising efficacy. Liquid biopsy provides surveillance of the EGFR mutation by disclosing the entire genetic landscape but tissue biopsy is still indispensable because of the considerable rate of false-negative plasma.

Keywords

Non-small cell lung cancer (NSCLC) Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) Acquired resistance Mechanism Strategy 

Abbreviations

EGFR TKI

Epidermal growth factor receptor tyrosine kinase inhibitor

NSCLC

Non-small cell lung cancer

PFS

Progression-free survival

OS

Overall survival

PD

Progressive disease

RR

Response rate

ATP

Adenosine triphosphate

ORR

Objective response rate

CNS

Central nervous system

AE

Adverse event

WT

Wild type

ILD

Interstitial lung disease

PD-1

Programmed death 1

PD-L1

Programmed death ligand 1

Notes

Acknowledgements

This study was funded by Talent Funding Program of Zhongshan Hospital of Fudan University.

Compliances with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical statements

This article does not contain any studies with human participations or animals performed by any of the authors.

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Department of Thoracic Surgery, Zhongshan HospitalFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Department of Thoracic SurgeryXuhui District Center Hospital of ShanghaiShanghaiChina

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