The role of T790M mutation in first- and second-line therapy of patients with EGFR-positive non-small cell lung cancer
Summary. Rare mutations of the EGFR (epidermal growth factor receptor) gene, in particular insertions in the 20 exon, account for approximately 10% of all oncogenic EGFR mutations in non-small cell lung cancer (NSCLC) — adenocarcinoma. The T790M mutation, which is better known as the EGFR I–II generation TKI resistance mutation, is also an insertion in the 20 exon and sometimes (about 2–4% of cases) can be detected de novo as a double mutation. However, it was shown that when ultra-sensitive methods have been used for genetic diagnosis, the prevalence of double mutations — T790М + Del19ex or L858R reaches 79%, which is a negative prognostic factor for patients with NSCLC. Therefore, the question arises today, what is the role of the T790M mutation in the I and II lines of therapy for EGFR-positive NSCLC and how the presence of double mutations affects the choice of treatment for patients with lung cancer. At the same time, it is known that insertions of exon 20 and T790M in particular are not sensitive to EGFR TKIs of early generations. However, III generation TKIs, in particular, osimertinib, show activity against tumors with these mutations and therefore may be a reasonable choice for the treatment of patients with NSCLC and these mutations.
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