Abstract
Tumor molecular profiling in patients with non-small cell lung cancer (NSCLC) is used to identify driver mutations, which lead to premature carcinogenesis in more than 80% of adenocarcinoma cases, including epidermal growth factor receptor (EGFR) mutations. Identification of specific somatic aberrations allows to personalize treatment. Personalization of treatment resulted in improvement of NSCLC outcomes. The aim of our study was to consider scientific data on modern concepts of treatment of patients with non-small cell lung cancer with previously detected oncogenic mutations, especially EGFR mutation. In our study we analyzed scientific papers and data of international scientific literature on the problem of lung cancer treatment. Methods used: scientific research, analytical and generalizing. Different drugs are used in treatment of lung cancer. Choice of treatment scheme depends on type and presence of mutations. Patients with advanced non-small-cell lung cancer and detected mutation in the EGFR can be treated with tyrosine kinase inhibitors (TKIs). Nowadays three first generation drugs are recommended by FDA: afatinib, erlotinib, gefitinib. They showed good clinical benefit. Most patients with metastatic NSCLC typically show disease progression after approximately 9 to 13 months of erlotinib, gefitinib, or afatinib therapy. The first and only commercially available third-generation EGFR TKI is оsimertinib - an oral drug, which selectively inhibits both EGFR-TKI and EGFR T790M resistance mutations. Nowadays scientists are in active investigation of mechanisms of acquired resistance to TKIs, but little is known yet. Clinical success can be observed in patients who were treated with TKIs. EGFR T790M is a mutation that leads to acquired resistance to EGFR TKI therapy. Its incidence is approximately 60% after disease progression on TKI drugs (erlotinib, gefitinib, or aphatinib). Third-generation EGFR TKIs demonstrate high efficacy, but acquired resistance development cannot be avoided. Mechanisms of acquired resistance to these agents are still investigated.
Highlights
Non-small cell lung cancer (NSCLC) occupies the leading positions among deaths from cancer [5, 9, 11, 27, 35, 42, 48]
epidermal growth factor receptor (EGFR) mutation testing is recommended in patients with glandular or adenosquamous tumor variant, for squamous cell carcinomas it is uncommon [12, 22]
Clinical success was observed in treatment with the first generation EGFR tyrosine kinase inhibitors (TKIs)
Summary
Non-small cell lung cancer (NSCLC) occupies the leading positions among deaths from cancer [5, 9, 11, 27, 35, 42, 48]. For patients with sensitizing EGFR mutations, the FDA has permitted the use of this drug as first-line therapy in the case of metastatic, recurrent, or progressive tumors [17, 19]. The disease controlled rate was higher in patients treated with osimertinib compared with standart chemotherapy (93% vs 74%) [10] It was found, that osimertinib showed good clinical benefits for treatment of patients with metastatic EGFR T790M-positive NSCLC with disease progression after or during TKI EGFR therapy. That osimertinib showed good clinical benefits for treatment of patients with metastatic EGFR T790M-positive NSCLC with disease progression after or during TKI EGFR therapy Rare these mutations or amplifications occurred together with T790M mutation [43, 46]
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