Modern treatment approaches of patients with NSCLC and «rare» EGFR mutations and own experience in the treatment of patients with an insertion in the 20th exon
Summary. To date, more than 200 different oncogenic mutations of the EGFR gene have been identified and studied, which are important for the development, progression and prognosis of the course of the oncological process. For a long time, the main attention was focused on the two most common oncogenic mutations in the catalytic domain of the epidermal growth factor receptor (EGFR): in exon 19 (Del746–750) (46% of cases) and in exon 21 (L858R) (38%). It was these studies that marked the beginning of targeted therapy for non-small cell lung cancer (NSCLC) and success in the treatment of not only metastatic but also resectable cases. Other variants of EGFR gene mutations account for 10–15% and are traditionally classified as «rare», but with the advent of improved sequencing technologies, the percentage of «rare» mutations reaches 30–44%. An insertion in the 20th exon of the EGFR gene is the most common type of «rare» mutation, which is found in approximately 10% of patients with EGFR-mutated NSCLC. At the same time, patients with insertions in the 20th EGFR exon demonstrate primary resistance to early-generation EGFR tyrosine kinase inhibitors (TKI) and have unsatisfactory clinical outcomes. We reviewed the features of the clinical course of NSCLC with an insertion in the 20th EGFR exon and the evolution of treatment methods for such patients. One of the drugs that demonstrates effectiveness against insertion in the 20th exon of EGFR is the third-generation TKI — osimertinib. Its key feature is a wide therapeutic window for mutated forms of EGFR, including insertions in the 20th exon, suggesting a potential therapeutic advantage as a targeted therapy in tumors of this type. The results of studies on the effectiveness of osimertinib in NSCLC with an insertion in the 20th exon of EGFR, as well as our own clinical experience in the treatment of patients with this mutation, are presented.
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