EGFR-TKIs in non-small-cell lung cancer: focus on clinical pharmacology and mechanisms of resistance

The clinical introduction of EGFR-TKIs within the oncologic armamentarium has changed the therapeutic landscape of non-small-cell lung cancer (NSCLC) creating widespread expectations both in patients and clinicians. However, several gaps in current understanding leave open important questions regarding the use of these drugs in clinical practice. For instance, there is uncertainty in regard to which EGFR-TKI should be given first in naive patients with EGFR-driven malignancies since different generations of drugs are available with different pharmacological profiles. Furthermore, acquired drug resistance may limit the therapeutic potential of EGFR-TKIs and the choice of the best treatment strategy after first-line treatment failure is still debated. This review article is aimed at describing the pharmacological properties of EGFR-TKIs and the current treatment options for NSCLC patients who develop acquired resistance. This information might be useful to design new rational and more effective pharmacological strategies in patients with EGFR-mutant NSCLC.