Personalized care for patients with EGFR-mutant nonsmall cell lung cancer - Navigating early to advanced disease management

Sep 23, 2026

Uploaded by Kurz

Activating mutations in the epidermal growth factor receptor (EGFR) gene have transformed lung cancer management by enabling targeted tyrosine kinase inhibitors (TKIs) that improve survival and reduce side effects versus conventional therapy. Advances now integrate TKIs across early-stage and locally advanced disease, while phase 3 trials examine combination strategies in metastatic settings. Despite gains in progression-free survival, toxicity and costs increase, making careful patient selection essential. Biomarker evidence, including co-mutations and circulating tumor DNA, supports more refined treatment decisions, and new insights into EGFR TKI resistance expand therapeutic options.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages23

Reading Time58 min

AccessFree to download

Introduction

Actionable EGFR alterations and precision medicine

EGFR mutation prevalence and demographic patterns

Clinical challenges in metastatic EGFR-mutant NSCLC

Personalized treatment goals and scope of the review

DOI: 10. 3322/caac.70024 REVIEW ARTICLE Personalized care for patients with EGFR-mutant nonsmall cell lung cancer: Navigating early to advanced disease management Maxime Borgeaud MD1 | Timothée Olivier MD 1 | Jair Bar MD, PhD2,3 | Stephanie Pei Li Saw MD, PhD4,5 | Kaushal Parikh MD6 | Giuseppe Luigi Banna MD7,8 | Claudio De Vito MD, PhD9 | Jill Feldman10 | Xiuning Le MD, PhD11 | Alfredo Addeo MD1 1Oncology Department, University Hospital Geneva, Geneva, Switzerland 2 Institute of Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel 3Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel 4Division of Medical Oncology, National Cancer Center Singapore, Singapore 5Duke-National University of Singapore Medical School, National University of Singapore, Singapore 6Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA 7Department of Oncology, Portsmouth Hospitals University National Health Service Trust, Portsmouth, UK 8Faculty of Science and Health, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK 9Pathology Department, University Hospital Geneva, Geneva, Switzerland 10Patient Advocate, EGFR Resisters, Deerfield, Illinois, USA 11Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence Alfredo Addeo, Department of Oncology, Geneva University Hospital, 4 GabriellePerret-Gentil Street, Geneva, Switzerland. Email: [alfredo.addeo@hug.ch](alfredo.addeo@hug.ch) Abstract The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene has revolutionized the management of lung cancer, enabling the development of targeted tyrosine kinase inhibitors (TKIs). These therapies offer improved survival and reduced side effects compared with conventional treatments. Recent advancements have significantly reshaped the treatment paradigm for EGFRmutant non-small cell lung cancer. TKIs are now incorporated into the management of early stage and locally advanced disease, and phase 3 trials have explored combination strategies in metastatic settings. Although these intensified approaches improve progression-free survival, they come with increased toxicity and higher costs, underscoring the need for precise patient selection to maximize benefit. Emerging data on biomarkers, such as co-mutations and circulating tumor DNA, show promise for refining treatment decisions. In addition, significant progress in understanding resistance mechanisms to EGFR TKIs has broadened therapeutic options. This review provides a comprehensive overview of the current landscape of This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2025 The Author(s). CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society. EGFR-mutant nonsmall cell lung cancer, highlighting recent breakthroughs and discussing strategies to optimize treatment based on the latest evidence. KEYWORDS activating mutations, epidermal growth factor receptor (EGFR), non-small cell lung cancer (NSCLC), tyrosine kinase inhibitors (TKIs) INTRODUCTION The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene introduced the concept of actionable alterationsin nonsmall cell lung cancer (NSCLC) and paved the way for precision medicine in lung cancer. Mutations in the tyrosine kinase domain of EGFR represent one of the most common druggable alterations in NSCLC. EGFR kinase domain mutations are found almost exclusively in lung adenocarcinomas (LUADs), with a prevalence ranging from 15% to 50% depending on ethnicity.1 They occur more commonly inpatients with no smoking history, femal

FAQs

Why do EGFR activating mutations matter in nonsmall cell lung cancer management?

They enable actionable, druggable alterations and support precision medicine. This discovery led to targeted tyrosine kinase inhibitors that improve survival and reduce side effects compared with conventional treatments.

How has the treatment role of TKIs expanded across disease stages?

TKIs are now incorporated for early stage and locally advanced disease. Phase 3 trials also explore combination strategies in metastatic settings.

What are the key trade-offs of intensified TKI strategies?

While intensified approaches can improve progression-free survival, they also increase toxicity and higher costs, which requires precise patient selection to maximize benefit.

Sep 23, 2026

Uploaded by Kurz