Abstract
Non-small-cell lung cancer (NSCLC) is the most common form of primary lung cancer. The discovery of several oncogenic driver mutations in patients with NSCLC has allowed the development of personalized treatments based on these specific molecular alterations, in particular in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene. Gefitinib, erlotinib, afatinib, and osimertinib are TK inhibitors (TKIs) that specifically target EGFR and are currently approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as first line treatment for sensitive EGFR-mutant patients. However, these four drugs are associated with severe adverse events (AEs) that can significantly impact patient health-related quality of life and patient monitoring. EGFR-TKIs are commonly used together with other types of medication that can substantially interact. Here, we review approaches used for the management of TKI-AEs in patients with advanced NSCLC to promote the benefits of treatments and minimize the risk of TKI treatment discontinuation. We also consider potential TKI–drug interactions and discuss the usefulness of plasma concentration monitoring TKIs based on chromatographic and mass spectrometry approaches to guide clinical decision-making. Adjusting the most appropriate therapeutic strategies and drug doses may improve the performance therapy and prognosis of patients with advanced EGFR-mutated NSCLC.
Highlights
Non-small-cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, with the majority of patients presenting with advanced disease at the time of diagnosis [1]
We focus on the pharmacokinetic (PK) data and known drug interactions for each of the currently available epidermal growth factor receptor (EGFR)-TK inhibitors (TKIs)
We summarize the most severe adverse effects observed with first, second, and third-generation EGFR-TKIs
Summary
Non-small-cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, with the majority of patients presenting with advanced disease at the time of diagnosis [1]. Advances in targeted and individualized treatment of NSCLC since the late 2000s have led to the development of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), such as first-generation reversible gefitinib (Iressa) [2] and erlotinib (Tarceva) [3], and second-generation irreversible afatinib (Giotrif) [4] These U.S Food and Drug Administration (FDA)-approved drugs exhibit higher efficacy in patients harboring specific activating molecular alterations in the tyrosine kinase domain of EGFR (exons 18–21). Osimertinib has been demonstrated to be more efficient than conventional EGFR-TKIs and has been rapidly approved as a first-line treatment of advanced EGFR-mutated NSCLC [11] These compounds are associated with the development of tumoral clone resistance after 6–17 months of therapy [12]. We discuss the role of oncologists in safely managing EGFR-TKIs use to ensure maximum patient benefit
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