Optimal sequence of application of epidermal growth factor receptor inhibitors in advanced non-small cell lung cancer patients with activating EGFR mutations

Background. Successful treatment of patients with EGFR-positive non-small cell lung cancer (NSCLC) is directly related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Currently, three generations of EGFR TKIs are used for treatment of EGFR-positive NSCLC. The issue of what drug or what sequence of its administration will be the optimal treatment option for a particular patient seems relevant. purpose: To analyze available data on the use of TKIs for the treatment of advanced EGFR-positive NSCLC patients, as well as to assess the possible mechanisms of resistance to them and determine the optimal sequence of EGFR TKI therapy. Material and Methods. The review includes data from randomized controlled trials, as well as data from real-world studies on the efficacy of EGFR TKIs and subsequent therapy options in cases of drug resistance. Results. The choice of the optimal first-line treatment option for patients with EGFR-positive NSCLC depends on many factors. To our opinion, afatinib therapy with subsequent osimertinib therapy allows maximal prolongation of low-toxic targeted therapy and delayed administration of cytostatic drugs in patients with T790M mutation. conclusion. Considering the dominant mechanism of resistance development (presence of EGFR -T790M mutation), the use of the second- and third-generation EGFR inhibitors seems to be an optimal treatment option for patients with activating EGFR mutations.