European and American Cancer Society guidelines recommend targeted therapy as the standard treatment for advanced non-small cell lung cancer (NSCLC) stage IV with positive molecular test results (i.e., proven oncogenic drivers). In 2004, an EGFR mutation was identified in lung cancer, becoming the first target of genome-directed therapy. Two mutations, deletions in exon 19 and the single amino acid substitution L858R in exon 21, together account for approximately 85% of the observed EGFR mutations in NSCLC and confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Currently, there are five EGFR TKIs from three generations approved and used in clinical practice: first-generation Erlotinib and Gefitinib; second-generation Afatinib and Dacomitinib; and third-generation Osimertinib. Afatinib is a P-gp and BCRP substrate, whereas the other EGFR TKIs undergo hepatic metabolism via cytochrome P450 (CYP) enzymes. Since the most frequently reported clinically relevant interactions are due to modulation of drug-metabolizing enzymes or transmembrane transporters, this presents a potential for drug-drug interactions of varying intensity that may influence the safety and/or therapeutic effect of the drugs. Hospital pharmacy professionals play a key role in the treatment of oncology patients receiving TKIs by detecting potential drug-drug interactions and adverse drug reactions early, as well as through patient education.
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