Abstract
Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic drivers in non-small-cell lung cancer (NSCLC). Significant developments have taken place which highlight the differences in tumor biology that exist between the mutant and wild-type subtypes of NSCLC. Patients with advanced EGFR-mutant NSCLC have a variety of EGFR-targeting agents available proven to treat their disease. This has led to superior patient outcomes when used as a monotherapy over traditional cytotoxic systemic therapy. Attempts at combining EGFR agents with other anticancer systemic treatment options, such as chemotherapy, antiangiogenic agents, and immunotherapy, have shown varied outcomes. Currently, no specific combination stands out to cause a shift away from the use of single-agent EGFR inhibitors in the first-line setting. Similarly, adjuvant EGFR inhibitors, are yet to significantly add to patient overall survival if used at earlier timepoints in the disease course. Liquid biopsy is an evolving technology with potential promise of being incorporated into the management paradigm of this disease. Data are emerging to suggest that this technique may be capable of identifying early resistance mechanisms and consequential disease progression on the basis of the analysis of blood-based circulating tumor cells.
Highlights
Treatment of lung cancer, with the adenocarcinoma subtype, has evolved significantly in recent years
This study reported a 2 year disease-free survival (DFS) in favor of erlotinib: 2 year DFS 81.4%, 95% confidence interval (CI) 69.6–93.1% for erlotinib; 2 year DFS 44.6%, 95% CI 26.9–62.4% for chemotherapy
A number of studies highlighted the use of circulating tumor DNA, circulating tumor cells (CTCs), and exosomes which may be used for a liquid biopsy [72,73]
Summary
With the adenocarcinoma subtype, has evolved significantly in recent years. A notable change is the analysis of patient tumors for the presence of oncogenic drivers [1]. The number of actionable mutations is steadily increasing, offering a more personalized approach to the management of patients with lung cancer [2,3]. Epidermal growth factor receptor (EGFR)-mutated lung cancer occurs in 15–20% of patients with adenocarcinoma and is most commonly associated with nonsmokers and those of Asian ethnicity. Targeted EGFR treatment offers superior outcomes and toxicity profiles compared to traditional cytotoxic-based treatments in those with advanced disease. We outline the underlying mechanisms of action of the various EGFR tyrosine kinase inhibitors (TKIs), clinical data, and the evolving role of liquid biopsy in this disease
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