Comparative review of drug–drug interactions with epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small-cell lung cancer

The development of small-molecule tyrosine kinase inhibitors (TKIs) that target the epidermal growth factor receptor (EGFR) has revolutionized the management of non-small-cell lung cancer (NSCLC). Because these drugs are commonly used in combination with other types of medication, the risk of clinically significant drug–drug interactions (DDIs) is an important consideration, especially for patients using multiple drugs for coexisting medical conditions. Clinicians need to be aware of the potential for clinically important DDIs when considering therapeutic options for individual patients. In this article, we describe the main mechanisms underlying DDIs with the EGFR-TKIs that are currently approved for the treatment of NSCLC, and, specifically, the potential for interactions mediated via effects on gastrointestinal pH, cytochrome P450-dependent metabolism, uridine diphosphate-glucuronosyltransferase, and transporter proteins. We review evidence of such DDIs with the currently approved EGFR-TKIs (gefitinib, erlotinib, afatinib, osimertinib, and icotinib) and discuss several information sources that are available online to aid clinical decision-making. We conclude by summarizing the most clinically relevant DDIs with these EFGR-TKIs and provide recommendations for managing, minimizing, or avoiding DDIs with the different agents.