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Series:   Elements in Molecular Oncology

EGFR-Directed Therapy in Lung Cancer

Published online by Cambridge University Press:  05 January 2023

So Yeon Kim ,
Daniel B. Costa ,
Daisuke Shibahara ,
Susumu Kobayashi  and
Balazs Halmos
So Yeon Kim
Affiliation:
Yale School of Medicine, Connecticut
Daniel B. Costa
Affiliation:
Harvard Medical School, Massachusetts
Daisuke Shibahara
Affiliation:
Harvard Medical School, Massachusetts
Susumu Kobayashi
Affiliation:
Harvard Medical School, Massachusetts
Balazs Halmos
Affiliation:
Albert Einstein College of Medicine, New York

Summary

Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a clinically important driver alteration affecting approximately one-third of lung cancer patients. Treatments for EGFR-exon 19 deletion and exon 21 L858R NSCLC have evolved over the last decade from first-generation reversible tyrosine kinase inhibitors (TKI) to third-generation irreversible TKIs, of which osimertinib has been the widely accepted as first-line therapy. Despite survival improvement seen with osimertinib and its efficacy against acquired T790M mutation, resistance through on-target and off-target pathways eventually develop. This Element describes the structural biology and pathophysiology of EGFR-mutant NSCLC and discusses past, current, and future treatment options in the metastatic, neoadjuvant, and adjuvant settings. It describes the biology and recently approved treatment for EGFR-exon 20 insertion mutation and the treatment for the uncommon exon 18 (G719X), 20 (S768I), and 21 (L861Q) mutations. It also outlines the promising clinical applications of circulating tumor DNA (ctDNA).
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Keywords

non-small cell lung cancerEgfrimmunotherapyresistance mechanismsosimertinib
Type
Element
Information
Series: Elements in Molecular Oncology
Online ISBN: 9781009342285
Publisher: Cambridge University Press
Print publication: 26 January 2023

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