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Abstract
Aim. To identify the mechanisms of resistance to osimertinib in circulating-tumor DNA (ctDNA).
Materials and Methods. An adapted method of complex genomic profiling for cDNA was used to conduct molecular genetic testing. The Trust study (a multicenter non-interventional retro- and prospective study of safety and efficacy of the Osimertinib administration in frames of Early Access Program (EAP) and real clinical practice in patients with locally advanced or metastatic non-small cell lung cancer that progressed during or after therapy with an EGFR tyrosine kinase I-II inhibitor, with confirmed Т790М positive mutation in EGFR gene) examined plasma samples from patients with disease progression on osimertinib. Molecular genetic testing was performed using an adapted comprehensive genomic profiling method for cDNA.
Results. A total of 62 patients with EGFR-positive non-small cell lung cancer after progression on osimertinib were included in the study. Only 35 samples were found to be suitable for testing. In 40 % of cases, genetic disorders were identified that predetermined the development of acquired resistance to osimertinib. EGFR-independent mechanisms prevailed – rearrangements in the RET gene (17.1 %) and MET amplification (11.4 %). EGFR-dependent mechanisms in the form of a tertiary C797S mutation were registered in 8.5 % of patients. A combination of two or more genetic disorders was detected in 22.8 % of patients.
Conclusion. The information obtained can be used to determine therapeutic tactics in patients after progression on osimertinib.
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