New possibilities in the treatment of EGFR mutation-positive non-small-cell lung cancer patients after the progression on a 1st and 2nd generation EGFR tyrosine kinase inhibitors

Abstract

Targeted therapy has opened a new era in treatment of patients with non-small-cell lung cancer associated with mutations of the epidermal growth factor receptor (EGFR) gene. However, most patients after starting targeted therapy develop progression within 10-12 months. The basic mechanisms of acquired resistance are known, the secondary mutation in exon 20 of EGFR gene is the leading cause in more than a half of the cases. To detect this mutation is important to repeat molecular testing, that, consequently, requiring re-biopsy. Liquid biopsy is considered as an alternative to re-biopsy. Osimertinib is a third generation EGFR-tyrosine kinase inhibitor, possessing antitumor activity, both, in respect of T790M-positive tumors and of tumors with mutations in exons 18, 19 and 21. In the randomized AURA3 trial, the use of osimertinib was effective in 71% of patients, the median progression free survival was 11 months after the progression on1st-line targeted therapy and was statistically significant than in case of chemotherapy application. Patients with brain metastases also show response to osimertinib treatment. In our study, 29 patients received osimertinib after the progression on targeted therapy of the 1st and 2nd generation tyrosine kinase inhibitors. Objective response was reported in 44.8% (complete response - 3.4%), stabilization - 51.7% and progression - 3.5%. We will show the results concerning the time without progression in the near future. The tolerance of treatment is good. Osimertinib has been approved for 1st-line targeted therapy treatment of patients with the T790M mutation upon progression in Russian Federation, thus we have new opportunities to improve the results of the treatment in this group of patients.