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World J Clin Oncol. Oct 24, 2021; 12(10): 912-925
Published online Oct 24, 2021. doi: 10.5306/wjco.v12.i10.912
Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer
Miguel J Sotelo, José Luis García, Cesar Torres-Mattos, Héctor Milián, Carlos Carracedo, María Ángeles González-Ruiz, Xabier Mielgo-Rubio, Juan Carlos Trujillo-Reyes, Felipe Couñago
Miguel J Sotelo, Department of Medical Oncology, Hospital María Auxiliadora; Department of Medical Oncology, Centro Oncológico Aliada; Oncological Research Unit, Clínica San Gabriel, Lima 15801, Peru
José Luis García, Department of Thoracic Surgery, Hospital Universitario La Princesa; Department of Thoracic Surgery, MD Anderson Cancer Center; Department of Thoracic Surgery, Hospital HM, Madrid 28006, Spain
Cesar Torres-Mattos, Department of Medical Oncology, Hospital Nacional Guillermo Almenara; Oncological Research Unit, Clínica San Gabriel, Lima 15033, Peru
Héctor Milián, Department of Thoracic Surgery, Hospital Universitario La Princesa, Madrid 28006, Spain
Carlos Carracedo, Department of Medical Oncology, Centro Oncológico Aliada, Lima 15036, Peru
María Ángeles González-Ruiz, Department of Radiation Oncology, Hospital Universitario Virgen Macarena, Sevilla 41009, Spain
Xabier Mielgo-Rubio, Department of Oncology, Hospital Universitario Fundación Alcorcón, Alcorcón 28922, Madrid, Spain
Juan Carlos Trujillo-Reyes, Department of Thoracic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona 08041, Spain
Felipe Couñago, Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid; Hospital La Luz; Universidad Europea de Madrid, Madrid 28223, Spain
Author contributions: Sotelo MJ performed the research and wrote the manuscript; Luis García J, Torres-Mattos C, Milián H, Carracedo C, González-Ruíz MA, Trujillo JC, Couñago F and Mielgo-Rubio X contributed critical review of the manuscript for important intellectual content and all authors approved the final version.
Conflict-of-interest statement: Dr. MIELGO-RUBIO reports personal fees and non-financial support from ROCHE, personal fees from ASTRA ZENECA, grants, personal fees and non-financial support from BMS, personal fees from MSD, personal fees from ABBOTT, personal fees from KIOWA-KIRIN, outside the submitted work. Rest of authors declares no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Miguel J Sotelo, MD, PhD, Department of Medical Oncology, Hospital María Auxiliadora; Department of Medical Oncology, Centro Oncológico Aliada; Oncological Research Unit, Clínica San Gabriel, Avda Miguel Iglesias 968, Lima 15801, Peru. miguel.sotelo.lezama@gmail.com
Received: April 16, 2021
Peer-review started: April 16, 2021
First decision: July 6, 2021
Revised: July 29, 2021
Accepted: September 16, 2021
Article in press: September 16, 2021
Published online: October 24, 2021
Processing time: 188 Days and 12.4 Hours
Abstract

Patients with early-stage non-small-cell lung cancer (NSCLC) are candidates for curative surgery; however, despite multiple advances in lung cancer management, recurrence rates remain high. Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival (OS), but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients. The high efficacy of tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor-mutated (EGFR) in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease. Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment, in patients with resected EGFR-mutated NSCLC, and shown that they significantly prolong disease-free survival (DFS), but this benefit does not translate to OS. Recently, an interim analysis of the ADAURA trial demonstrated that, surprisingly, osimertinib improved DFS. This led to the study being stopped early, leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup. These targeted agents are also being evaluated in locally-advanced disease, with promising results, although prospective studies with larger sample sizes are needed to confirm these results. In this article, we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.

Keywords: Non-small-cell lung cancer; Early stage; Epidermal growth factor receptor-mutated; Epidermal growth factor receptor-mutated-tyrosine kinase inhibitor; Adjuvant; Neoadjuvant

Core Tip: Epidermal growth factor receptor-mutated (EGFR) tyrosine kinase inhibitors (TKIs) have changed the natural history of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). Multiple clinical trials conducted in the adjuvant setting have shown that EGFR TKIs prolong disease-free survival (DFS) but not overall survival (OS). Osimertinib demonstrated a surprising improvement in DFS in an interim analysis of the ADAURA study, which led to the study being stopped early, and left many unanswered questions about its potential effect on OS. Locally-advanced disease is also an attractive situation for assessment of the efficacy of these agents, with encouraging results so far. We discuss the recent advances in the management of early-stage EGFR-mutated NSCLC.