Drug-drug interactions of tyrosine kinase inhibitors in treatment of non-small-cell lung carcinoma

The development of tyrosine kinase inhibitors has revolutionized the treatment strategy in patients with non-small cell lung cancer with activating EGFR mutations, ALK or ROS-1 gene rearrangements. The Food and Drug Administration and European Medicines Agency hove approved several inhibitors for the treatment of non-small cell lung cancer: five tyrosine kinase inhibitors targeting EGFR (erlotinib, gefitinib, afatinib, osimertinib and dacomitinib) and six tyrosine kinase inhibitors targeting ALK (crizotinib, ceritinib, alectinib, brigatinib, lorlatinib and entrectinib). Interestingly, these tyrosine kinase inhibitor treatments are administered orally. While this route of administration improves the treatment flexibility and provides a comfortable and preferable option for patients, it also increases the risk of drug-drug interactions. The latter may result in changes in pharmacokinetics or phormacodynamks of the tyrosine kinase inhibitors or their concomitant treatments, with subsequent risks of increasing their toxicity and/or reducing their effectiveness. This review provides an overview of drug-drug interactions with tyrosine kinase inhibitors targeting EGFR and ALK, as well as practical recommendations to guide oncologists and clinical pharmacists in the process of managing drug-drug interactions during the treatment of non-small cell lung cancer with tyrosine kinase inhibitors.