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Objective: to evaluate the pharmacoeconomic efficacy of “atezolizumab + bevacizumab + paclitaxel + carboplatin” drug combination compared to “pembrolizumab + pemetrexed + carboplatin” combination in adult patients with non-small cell lung cancer (NSCLC) in the first line of therapy.Material and methods. The modeling was applied for cost minimization analyzis of using compared therapy regimens with comparable efficacy, and to estimate the impact on the healthcare budget when increasing the proportion of patients in the target population receiving “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination. Published adjusted indirect comparison data were used in modeling. The calculations were based on the registered prices according to the state register of maximum selling prices.Results. The use of “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination instead of “pembrolizumab + pemetrexed + carboplatin” combination will decrease the direct medical costs of therapy per 1 patient for 2 years by 28,165.00 rubles (–0.4%). The budget impact analysis showed that an increase in the proportion of patients receiving “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination from 50% (current therapy practice) to 100% (considered therapy practice) will reduce the budget load for the population of 6,240 patients over 2 years by 256.1 million rubles (–0.64%).Conclusion. The results of pharmacoeconomic analysis demonstrated that the use of “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination in first-line therapy for metastatic NSCLC is economically feasible and reduces the load on the budget compared to “pembrolizu- mab + pemetrexed + carboplatin” scheme.

Objectives. To systematically review the complex relationship between cardiovascular comorbidities and lung cancer, focusing on their impact on patient prognosis, treatment outcomes, and quality of life, with special emphasis on non-small-cell lung cancer (NSCLC). Methods. A comprehensive literature search was conducted across databases such as PubMed, MEDLINE, and Google Scholar. A total of 137 studies examining the following aspects were included: Prevalence of cardiovascular comorbidities (e.g., coronary artery disease, heart failure, arrhythmias, valvular disease, thromboembolic events) in lung cancer patients; Prognostic implications of cardiovascular comorbidities across different stages of lung cancer; Impact of cardiovascular complications arising from cancer treatments (chemotherapy, radiotherapy); Assessment of quality of life in lung cancer patients with cardiovascular comorbidities. Results. The prevalence of various cardiovascular comorbidities in lung cancer patients across different stages remains high. Prognostic impact of pre-existing cardiovascular comorbidities, especially in early-stage lung cancer remains negative. Cancer therapies can exacerbate existing cardiovascular conditions or induce new complications, significantly reducing the quality of life in patients with both lung cancer and cardiovascular comorbidities. Conclusions. To mitigate the risk of cardiovascular complications in lung cancer patients with comorbidities, a comprehensive approach is necessary. This includes proactive cardiovascular risk assessment and management throughout all stages of lung cancer treatment, the development of treatment strategies tailored to individual patient risk profiles, and continued research into the underlying mechanisms of cardiovascular complications in lung cancer.

Background: Against limited effectiveness of known oncological treatment such as chemio-and radiotherapy or surgery, new ways of treatment, such as for example immunotherapy has developed. Usage of immune checkpoint inhibitors (ICPIs), resulting in overactivation of immune system, may significantly raise efficacy of oncological treatment, but simultaneously predispose to occurrence various autoimmunological health complications. Adverse actions of the therapy may affect multiple organs and systems, with the presented example of immune-related neurological complication, myasthenia gravis. This relatively rare condition may be severe, life-threatening illness. Case report: We present a case of 66-year-old male patient diagnosted with a large tumor histopathologically assessed as squamous cell carcinoma. Due to ineffectiveness of implemented chemio- and radiotherapy, he was qualified for anti-PD1 immunotherapy with nivolumab. General treatment tolerance was very good with positive antineoplastic effect. Autoimmune hypothyroidism has emerged, therefore levothyroxine therapy has been implemented. After about a year of using immunotherapy, significant weakness and decrease in muscle strength has appeared, subsequently, immunotheraphy-related myasthenia gravis was raised. Improvement in the patient's condition was achieved after initiating pyridostigmine treatment. Cessation of antineoplastic treatment wasn’t necessary, what is unusual. Conclusions: Undeniably myastenia gravis may determine serious, life-threatening adverse effect of immunotherapy. Usually requires withdrawal of applied antioncological treatment, and should be treated with immunomodulators, immunosuppressants or intravenous immunoglobulins or plasmaphaeresis, however – as we present- in some cases may be properly cured only with pyridostygmine.

Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase domain, which has shown effectiveness in the treatment of non-small cell lung cancer with activating EGFR mutation. A number of large randomized studies have shown a significant increase in survival without progression in the use of erlotinib and other tyrosine kinase inhibitors in comparison with standard chemotherapy. At the same time, there were no differences in the overall survival rate, which is due to the high frequency of tyrosine kinase inhibitors use in subsequent therapy lines in patients who had progression during the first-line chemotherapy. At the same time, this retrospective study showed an obvious (more than doubling) increase in the overall survival rate of patients receiving treatment with tyrosine kinase inhibitors as compared to historical control. There were no significant differences between the first and second generation tyrosine kinase inhibitors. Mutation of T790M is one of the main mechanisms of resistance to erlotinib. When progressing against the background of erlotinib treatment, the third generation tyrosine kinase inhibitor osimertinib is effective in case of T790M mutation detection. The combination of erlotinib with bevacizumab leads to an increase in survival without progression, without affecting the overall survival rate. The combined use of chemotherapy and tyrosine kinase inhibitors requires further study. An example of a long-term effect on the background of erlotinib treatment in a patient with non-small-cell lung cancer of stage IV with EGFR mutation is given. The total duration of treatment was 68 months, including the therapy with erlotinib in combination with bevacizumab and local radiation therapy on the progression zone (rib metastasis), which lasted for 21 months against the background of the indolent course of the disease.

For a long time, the standards of first-line drug therapy for patients with advanced non-small-cell lung cancer (NSCLC), excluding cases of mutations of EGFR, ALK and ROS1, were platinum-containing regimens. However, the chemotherapeutic regimes used in the therapy of the first line therapy of NSCLC have insignificant efficiency, and therefore the total survival rate of patients remains low: the response rate varies from 12 to 37%, the median survival rate without progression is from 4 to 7 months, the median of total survival – from 8 to 13 months.The use of a new class of immunooncologic drugs called immune checkpoint inhibitors has expanded the treatment options for NSCLC patients. One of the most effective immunooncologic drugs is pembrolizumab, which showed a clear advantage in increasing the overall survival rate in comparison with chemotherapy – median was 30.0 months vs. 14.2 months. (RR 0,63; 95% CI: 0,47–0,86; р = 0,002).The article presents the clinical observation of a patient with the diagnosis of «adenocarcinoma of the upper part of the right lung of the IIIA stage» with the progression developed in two years after the combined treatment. The patient received 29 courses of pembrolizumab immunotherapy in the first line of therapy with partial response achievement.The presented clinical observation confirms the efficacy of pembrolizumab in the first line of NSCLC treatment. Due to the immunotherapy with pembrolizumab there is no progression of the disease during more than 22 months with satisfactory quality of life and absence of pronounced toxicity of treatment.

Molecularly targeted therapy with tyrosine kinase inhibitors (TKI) has been recognized as the optimal treatment option for patients with EGFR-positive non-small-cell lung cancer (NSCLC). At present, 5 drugs of this group are available: first generation – erlotinib and gefitinib, second generation – afatinib and dacomitinib (not registered in Russia), and third generation – osimertinib. The drugs have some peculiarities, this refers to their antitumor activity, safety profile, and resistance mechanisms. Knowledge of these differences is necessary to determine a rational treatment plan. Gefitinib and erlotinib increase the time before progression compared to standard chemotherapy, but do not affect the overall survival rate. Afatinib significantly increases the time before progression, and in the cohort of patients with deletion in the 19th exon – the overall survival rate. Dacomitinib was more effective than gefitinib in terms of time before progression and total survival. On average, the disease progresses after a year and a half of successful treatment. The dominant mechanism of resistance development to TKI of the first and second generation consists in accumulation of mutation of the gatekeeper gene T790M. Most often it is determined in patients with deletion in the 19th exon (Del19). Osimertinib has proved to be effective against tumors not only with activating mutations, but also with T790M resistance mutation, and with minimal activity to EGFR «wild» type receptors. The first indication that it was registered was progression on targeted therapy with first and second generation drugs caused by the secondary mutation of T790M. Later, the advantage of osimertinib compared to gefitinib/erlotinib in untreated EGFR-positive patients was proved. Thus, there are at least two main options for treatment tactics: the consistent use of second and third generation drugs or prescription of osimertinib in the first line with subsequent chemotherapy. Evaluation and consideration of known prognostic factors will allow choosing the optimal tactics for a particular patient.

In 2017 the first published PFS results of PACIFIC study demonstrated new opportunities of immunotherapy in locally-advanced unresectable non-small-cell lung cancer (NSCLC) after chemoradiation (CRT). The positive overall survival results in this trial were received next year. This trial has become the first positive study in the more then 10 years after failure of all trials which investigated different approaches for improvement efficacy of standard CRT (induction therapy, consolidation therapy, target therapy, increased RT dose). The PACIFIC trial has opened new opportunities to improve outcomes in this patient’s population. Durvalumab was registered in Russia in July 2019, however clinical experience of durvalumab administration is still limited and we need to build expertise in this field. In this article we present the first example of durvalumab therapy in post CRT period in Bashkortostan real clinical practices. Patient with IIIB st NSCLC started durvalumab therapy after standard CRT. The complete response was registered after 4 months of therapy and currently after 9 months of therapy it is still remain.

Ceritinib is the second ALK tyrosine kinase inhibitor after crizotinib, registered in the Russian Federation for the treatment of ALKpositive patients with non-small cell lung cancer (NSCLC). Later alectinib was registered. Thus, we have the opportunity, firstly, to continue targeted therapy with second-generation drugs after progression on crizotinib, and secondly, the appointment of more active drugs in the first line provides the best results of treatment.

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.

The objective of the study is to substantiate the applying of broncho- and angioplasty lobectomy as an alternative to pneumonectomy in NSCLC.Material and methods. The results of treatment of two comparable groups of patients with NSCLC were presented. In one group, patients underwent broncho- or angioplasty lobectomies (group A), in another – pneumonectomy (group B). The number of complications, overall and disease-free survival in both groups, as well as the factors affected the results were analyzed.Results. The number of postoperative complications in group A and group B was 12.5 % and 15.6 %, respectively. The median of disease-free survival and overall survival in both groups did not differ meaningfully, consisting of 20 months and 48 months in group A, and 19 months and 25 months in group B (p=0.91) and (p=0.97). The results of treatment were meaningfully affected only by the stage of the disease (p=0.017) and multidisciplinary treatment (p=0.007), including chemotherapy and radiation therapy.Conclusions. Performing of broncho- and angioplasty lobectomies can be justified as an alternative to lung removal in NSCLC within the multidisciplinary treatment.

Randomized clinical trials results have shown the advantage of non-selective EGFR tyrosine kinase inhibitor 2nd generation – afatinib compared with platinum-based chemotherapy in adenocarcinoma EGFR-positive patients in both the first and second-line of treatment. Shown significant improvement in PFS compared with standard platinum contain regimen and gefitinib in the first line of treatment. Also afatinib demonstrated the efficacy in the second line of treatment of squamous cell carcinoma of lung. The advantage of OS demonstrated in the subgroup of patients with Del19 in the global randomized clinical trials. According to the local experience FSBSI «Russian Cancer Research Center n.a. N.N.Blokhin» ORR afatinib therapy was 62.7% in the tumor growth control 94.1%. Median PFS – 18.0 months. The most common adverse events observed a rash, paronychia, and diarrhea requiring dose reduction of up to 30 and 20 mg / day, 34.5% and 16.4% of patients, espectively. On the whole, marked by a favorable toxicity profile and improve the quality of patients life.

The aspects of chemotherapy and erlotinib combination to treatment of non-small-cell lung cancer (NSCLC) are examined in the article. Mechanisms of ITK resistance acquiring and potential ways to its overcoming are discussed. In the randomized clinical trial FASTACT-II the intercalated combination of chemotherapy and erlotinib was used in the 1st line treatment of NSCLC. The efficacy of new approach was proved to Asian patients with EGFR mutated NSCLC.

Targeted cancer therapy directed at individual targets is often accompanied by the rapid development of drug resistance. The development of a new generation of antitumor drugs involves the search for many targets simultaneously to block or, conversely, restore their activity. In this regard, simultaneous analysis of gene expression in a complex network of interactions, primarily cell cycle control elements, is relevant for the search of specific molecular markers for the differential diagnosis of adenocarcinoma (ADC) and squamous cell lung cancer (SCC), as well as new targets for therapy. In this paper we performed an extended quantitative analysis of the expression of two suppressor genes, CTDSPL and its target RB1, as well as 84 genes of the main participants of the p16^(INK4A)-Cdk/cyclin D1-Rb and p53/p21^(Waf1) signaling pathways in the histological types of non-small-cell lung cancer (NSCLC), i.e., ADC and SCC, using the special panel of the Human Cell Cycle Regulation Panel. The expression profile of some genes shows the specificity to the histological type of NSCLC and the presence of metastases. The genes with a significantly increased expression that affect the activity of Rb (cyclins, cyclin-dependent kinases, their activators, inhibitors, etc.) can serve as potential targets for combined therapy of both ADC and SCC.