EVOLUTION OF DRUG THERAPY FOR LUNG CANCER WITH EGFR INHIBITORS: NEW ASPECTS
Authors: M.L. Stepanova, L.V. Khalicova, A.S. Zhabina, F.V. Moiseenko
One of the main events in the last 20 years in the treatment of NSCLC is the discovery in some patients of activating mutations of the epidermal growth factor receptor (EGFR). The use of tyrosine kinase inhibitors (TKI) significantly improved both the frequency of the objective response, the time to progression, and overall survival. When applying the 1st and 2nd generation EKFR TKI (gefitinib, erlotinib, afatinib) in patients with NSCLC associated with EGFR mutations, after 8–12 months, resistance to EGFR TKI therapy develops. Among the large number of identified molecular disorders that determine the loss of sensitivity of the tumor to therapy, the most frequent is the appearance of the T790M EGFR mutation. The first targeted drug that was approved for clinical use in patients with NSCLC who had previously received EGFR TKI was osimertinib, an irreversible third-generation EGFR tyrosine kinase inhibitor that binds to cysteine at 797 position of the EGFR tyrosine kinase. One of the key aspects is that only 73–77% of patients can receive treatment for EGFR+ NSCLC in the second line, since some patients may die from the progression of the process against he background of first-line or second-generation TKI therapy or objective status not meeting the criteria for prescribing osimertinib. The review will also present the clinical cases of the use of osimertinib, both in the first and in the second line of drug treatment in EGFR NSCLC.