Treatment Strategies for Non-Small Cell Lung Cancer with Common EGFR Mutations: A Review of the History of EGFR TKIs Approval and Emerging Data

Abstract

The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC in the first-line setting, therapy selection after progression on EGFR TKIs remains complex. Multiple groups are investigating novel therapies and drug combinations to determine the optimal therapy and treatment sequence for these patients. In this review, we summarize the landmark trials and history of the approval of EGFR TKIs, their efficacy and tolerability, and the role of these therapies in patients with central nervous system metastasis. We also briefly discuss the mechanisms of resistance to EGFR TKIs, ongoing attempts to overcome resistance and improve outcomes, and finalize by offering treatment sequencing recommendations.

Keywords: EGFR TKIs; EGFR mutations; non-small cell lung cancer; targeted therapies; therapy sequencing.

Figure 1

Timeline depicting the publication of landmark trials on anti-EGFR TKIs, approval by the FDA and EMA, and publication of data pertaining novel therapies; EMA, European Medicines Agency; FDA, Food and Drugs Administration; TKIs, tyrosine kinase inhibitors. Created with BioRender.com, accessed on 8 January 2023.