Introduction. Hepatocellular cancer in the Russian Federation remains an important problem due to the high one-year mortality rate, which is 61.9%. Рercentage of advanced stages of newly diagnosed patients – about 60%. We present the results combination therapy atezolizumab + bevacizumab in the first line in patients with HCC and unfavorable prognostic factors.
Aim. To evaluate the efficacy of using the anti-VEGF/PD-L1 regimen of atezolizumab in combination with bevacizumab as first-line therapy in 23 patients with HCC and tumor thrombosis of the portal vein in real clinical practice.
Materials and methods. The material of Blokhin National Medical Research Center of Oncology on the 23 patients with advanced HCC and tumor thrombosis of the portal vein, we receive the first line of therapy Atezolizumab 1200 mg + Bevacizumab 15 mg/kg 1 time in 21 days until progression or until intolerable toxicity. Efficiency was assessed according to RECIST 1.1 criteria. Analysis and statistical processing of the study results was carried out using the SPSS Statistics 23.0 program, based on the collected database. Survival analysis was performed using the Kaplan-Meier method. Descriptive statistics methods were used to analyze the socio-demographic and clinical characteristics of patients.
Results. At median follow-up, one-year survival is estimated at 51.6%. Median progression-to-progression survival in the poor prognosis group was 13.2 months. The median overall survival was not reached. Efficacy of therapy: a partial response registered in 4 (17.5%), stabilization in 16 (65.5%), progression in 3 (13%). Grade 3 adverse events were detected in 6 (26%) patients. Cases of arterial hypertension of the 3 were observed in 2 patients (9%); bleeding from esophageal varices of the 3rd degree in 3 patients (13%); only 1 patient (4%) had autoimmune hepatitis, grade 3 diarrhea in one patient (4%).
Conclusions. The use of atezolizumab + bevacizumab shows effective efficacy even in the group of patients with HCC complicated by thrombosis of the branches and trunk of the portal vein. Moreover, progression-free overall survival was better than in patients with distal portal vein thrombosis.

Lorlatinib is a new third-generation tyrosine kinase (TKI) inhibitor of ALK/ROS1, which has antitumour activity against most of the known mutations of resistance to crizotinib and second-generation TKI, as well as high intracranial efficacy. The safety of lorlatinib was evaluated in a multi-cohort phase I study involving 295 patients receiving the recommended dose of lorlatinib 100 mg once a day. Adverse events of lorlatinib were mainly mild to moderate severity. The most frequent complications – hypercholesterolemia (82.4%), hypertriglyceridemia (60.7%), edema (51.2%), peripheral neuropathy (43.7%) and side effects from the central nervous system (39.7%), were reversible and well controlled by dose modification and concomitant therapy, as evidenced by the low frequency of discontinuation of therapy due to adverse reactions. The majority of patients (81.0%) required the appointment of at least one hypolipidemic drug. When prescribing concomitant therapy, the possibility of drug interaction with lorlatinib, whose metabolism is carried out with the participation of specific CYP450 enzymes, should also be taken into account. Based on the presented results, an expert consensus opinion was developed on the correction of the main adverse reactions, including hyperlipidemia, complications from the central nervous system, weight gain, edema, peripheral neuropathy and others. No new adverse events were reported in the CROWN Phase III study conducted later. Lorlatinib has a characteristic toxicity profile, which must be taken into account for successful long-term targeted therapy while maintaining a good quality of life for patients. In the Russian Federation, the drug is approved for use in a wide clinical practice both for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) in the first line, and after progression to second-generation TKI. The article presents recommendations for the correction of the main adverse events of lorlatinib, as well as their own experience in managing patients.

Trastuzumab deruxtecan is a new generation Her2-directed antibody-cytostatic conjugate. The unique structure of the molecule, innovative pharmacokinetic and pharmacodynamic properties of the drug allows its effect to be extended not only to the target cells, but also to nearby tumour cells, causing their death. This phenomenon has become known as the abscopal effect, due to which the drug demonstrates effectiveness regardless of the degree of Her2 expression. In clinical trials, trastuzumab deruxtecan therapy significantly outperformed the standard treatment options in patients with Her2-positive breast cancer. Thus, the median time to progression was 17.8 months in patients who were exposed to multiple lines of therapy, including trastuzumab-emtansine, vs 6.9 months in the control group treated with the combination of capecitabine and anti-Her2 agents (RR 0.36, 95% CI 0.28–0.45), which has resulted in a significant prolongation of patients’ lives. The median overall survival reached 39.2 months, while it remained at the level of 26.5 months in the control group (RR 0.6575; 95% CI 0.5023–0.8605; p = 0.0021). In a direct comparison of treatment, trastuzumab deruxtecan was superior to trastuzumab emtansine, significantly increasing the median progression-free survival by 4 times: 28.8 vs. 6.8 months (RR 0.33, 95% CI 0.26–0.43). It also had advantages in terms of objective response rates, quality of life measures, and overall survival. Trastuzumab deruxtecan demonstrated high efficacy in the treatment of HER2-low tumours (Her2-low mBC), surpassing the standard chemotherapy options in all evaluated parameters in pre-treated patients. This article presents the results of
the main clinical trials of trastuzumab derukstecan, additionally discusses its efficacy in CNS metastatic lesions, highlights the safety issues of the drug.

Opportunities in the treatment of patients with metastatic non-small cell lung cancer (NSCLC) are expanding every year. New targets are em erging for molecular-directed antitumor therapy, the so-called targeted therapy. One of such promising targets is damage to the MET gene. Taking into account the large number of active targets in NSCLC, the time factor and the limited amount of tumor material, conducting extensive genomic testing using NGS is preferable to routine diagnostic methods.Mutation in the form of omission of the 14 exon of MET (METex14) occurs with a frequency of 3–4%, amplification of the MET gene – in 2–4% of cases. There is evidence that these disorders correlate with a poor prognosis. At the same time, the METex14 mutation and a high level of copyness are potential predictor markers for the response to capmatinib. For molecular genetic testing, the next-generation sequencing method is optimal, which makes it possible to detect multiple, including rare disorders. Capmatinib is a low molecular weight selective reversible MET inhibitor. In preclinical studies, the drug proved effective against various types of activation of the MET signaling pathway. Clinical studies have confirmed its high antitumor activity. In the GEOMETRY mono1 study, the objective response (OR) in patients with the METex14 mutation as the first line was among 68%, in pretreated patients – 41%, with a median response duration of 12.6 months and 9.7 months, respectively. The drug demonstrated high intracranial activity, regardless of whether radiation therapy was previously performed or not. Objective antitumor response and clinical improvement to targeted therapy with capmatinib are realized fairly quickly. The results obtained during the clinical trial were reproduced in routine practice. The drug has an acceptable toxicity profile. Capmatinib is the first and so far the only drug in the Russian Federation approved for the treatment of patients with a mutation of the MET gene.

Hormone therapy alone or in combination with targeted agents (CDK4/6 inhibitors, alpelisib, everolimus) is currently the standard treatment of metastatic luminal Her2-negative breast cancer. Aromatase inhibitors and fulvestrant are the main hormone therapy agents. Fulvestrant belongs to a special class of antiestrogens – selective estrogen receptor degraders (SERD) and does not have estrogen receptor agonist activity, unlike tamoxifen. In addition, the efficacy of fulvestrant does not depend on the presence of ESR1 mutations in the tumor. The combination of aromatase inhibitors with CDK4/6 inhibitors is the standard first-line treatment in patients with hormone-sensitive tumors, that is, with progression of more than 1 year after the end of adjuvant hormone therapy. Whereas fulvestrant ± CDK4/6 inhibitors are used for disease progression on adjuvant hormonal therapy in the 1st line or as 2nd line for progression on aromatase inhibitor therapy for metastatic cancer. The choice of treatment for patients with a PIK3CA mutation with progression on the 1st line of fulvestrant with a CDK4/6 inhibitor is difficult. This article presents a clinical example of the use of a combination of fulvestrant and alpelisib in a patient with secondary hormone resistance (progression on the adjuvant therapy with aromatase inhibitors) and progression on the first-line therapy with fulvestrant and palbociclib. Carrying out therapy with fulvestrant and alpelisib as the 2nd line provided a long-term (for 14 months) stabilization of the tumor process.

Immune checkpoint inhibitors have revolutionized the treatment of urothelial carcinoma. They are now part of the standard of care for locally advanced or metastatic urothelial carcinoma. Maintenance therapy with avelumab has been found to be the most effective compared to other immune checkpoint inhibitors. To date, platinum-containing chemotherapy followed by maintenance therapy with avelumab is the only regimen that has significantly improved overall survival in patients with advanced bladder cancer. The article presents the experience of maintenance therapy with avelumab on the example of 3 clinical cases of patients with inoperable forms of urothelial carcinoma. The experience of treating 3 patients who achieved stabilization with standard chemotherapy and received maintenance therapy with avelumab was retrospectively analyzed. The age of the patients ranged from 66 to 79 years, the study included two men and one woman. In two cases, muscle-invasive bladder cancer was initially verified, in one – progression 7 years after the start of treatment for non-muscle-invasive bladder cancer. Only in one of the cases, the volumetric formation of the bladder was radically removed, while distant metastases were detected 20 months after the operation, the rest of the patients did not receive radical treatment. The general condition allowed all patients to receive a full course of platinum-containing chemotherapy (gemcitabine + cisplatin or gemcitabine + carboplatin), partial remission was achieved. Maintenance immunotherapy with avelumab was started within a month of completion of chemotherapy. The duration of maintenance therapy currently ranges from 3 to 17 months; stabilization of the oncological process has been achieved in all cases. No clinically significant adverse side effects were noted in any of the cases. Our experience of maintenance immunotherapy with avelumab corresponds to world practice and illustrates the efficacy and safety of this drug.

The development of poly(ADP‐ribose) polymerase (PARP) inhibitors has been the most significant breakthrough in the treatment of advanced ovarian cancer over recent decades, with olaparib being the first drug of this class. The drug showed its efficacy at many stages of the treatment of various oncological diseases, but its maximum clinical efficacy is demonstrated in the initial treatment of BRCA-associated or HRD-positive ovarian cancer. In the phase III SOLO1 (n = 391) and PAOLA-1 (n = 806) clinical trials, treatment with olaparib reduced the relative risk of disease progression by 67% and 59%, and the risk of death by 45% and 38%, respectively. At the same time, the treatment of patients with disease progression after therapy with PARP inhibitors causes reasonable concerns in clinicians, which is associated with many aspects, primarily with the lack of individually developed approaches to the management of this category of patients. This discussion article through the example of the treatment of a particular patient allows to summarize the current data on the features of the tumour process after disease progression on PARP inhibitors and possible ways to resolve the issue of drug resistance in such patients. In the clinical case under discussion, the maintenance therapy with olaparib after combination treatment in a 50-year-old woman with metachronous multiple primary BRCA-associated malignancies (breast cancer in 2005, ovarian cancer in 2018) allowed to achieve a 2-year cancer remission, after which the oligoprogression of ovarian cancer was observed. PET-CT showed a left iliac lymph node metastasis without other progressive manifestations of the disease, after which a left laparoscopic iliac lymphadenectomy was performed, and the olaparib therapy was continued until progression or intolerable toxicity. The duration of olaparib therapy from the date when the local treatment was performed is 23 months as of this writing. The article states the detailed rationale behind choosing the non-standard management and presents the results of recent studies that support the decisions made.

Chemotherapy-induced nausea and vomiting (CINV) is a side effect of cancer treatment, affecting up to 40% of patients. Nausea and vomiting are the most dangerous and also the most common side effects among patients undergoing chemotherapy. CINV remains one of the most worrisome syndromes associated with cancer therapy and can lead to dehydration, electrolyte imbalances, malnutrition, and metabolic disorders. Risk factors for developing CINV include the patient’s gender and age, a history of CINV, and the emetogenicity and timing of chemotherapy. Options for preventing CINV are 5-HT3 receptor antagonists (i.e., ondansetron, granisetron, palonosetron) in combination with corticosteroids (i.e., dexamethasone) or additionally in combination with NK1 receptor antagonists (i.e., aprepitant, fosaprepitant, netupitant, rolapitant). Palonosetron is a selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. The effectiveness of palonosetron for delayed nausea and vomiting is also supported by the results of three randomized trials that demonstrated no side effects of the simplified regimen with palonosetron and single dose dexamethasone for the control of CINV associated with moderately emetogenic chemotherapy or AC regimen. A clinical observation of the treatment of a young patient with breast cancer is given. After the first course of chemotherapy, the patient developed a rather serious complication in the form of vomiting, which required hospitalization for infusion therapy. The above clinical observation demonstrates the effectiveness of palonosetron in neo-adjuvant chemotherapy in a young patient, which made it possible to complete the entire course of treatment. After completion of neo-adjuvant chemotherapy, a radical operation was performed and a complete morphological response was noted.

Most patients with multiple myeloma (MM) suffer from chronic pain of varying degrees of intensity at every stage of the natural disease process. Osteolytic bone lesions are one of the most common complications of MM. The bone disease visualized by PET/CT and MRI affects up to 90% of newly diagnosed MM patients, increasing the risk of the development of skeletal-related events. Pathological fractures and spinal cord compression occur in 17% and 6% of patients, respectively. Bone pain is explained by an increase in pressure in the bone marrow, the release of chemical mediators by myeloma plasma cells, and the occurrence of microcracks in the bones, indirectly to a violation of local metabolism. Management of myeloma bone disease includes anti-myeloma chemotherapy and radiotherapy, antiresorptive therapy with bisphosphonates or denosumab, and direct pharmacological pain correction. Patients with pathological vertebral fractures and without spinal cord compression should be considered for vertebroplasty or kyphoplasty. The use of proteasome inhibitors and monoclonal antibodies for the treatment of MM is associated with a risk of herpes simplex virus (HSV) and varicella-zoster virus (VZV) reactivation. The result of the healing of herpetic eruptions in some patients will be the development of postherpetic neuralgia, manifested by excruciating pain for months or years. Moreover, the treatment with proteasome inhibitor bortezomib is often associated with the development of long-term persistent peripheral neuropathy, often complicated by pain. According to their neurobiological and clinical features, pain is classified into nociceptive, neuropathic, and functional. Bone pain is nociceptive and for postherpetic and chemotherapy-induced neuropathy, the neuropathic component is more significant. Opioids are the drugs of choice for moderate to severe nociceptive pain, while anticonvulsants and antidepressants are the most commonly used adjuvants for neuropathic pain. This review summarizes information on the pathophysiology of various types of pain syndrome in patients with MM, as well as on modern approaches to the prevention and treatment of complications. The issues of the pharmacology of opioid analgesics are discussed. The review concludes with data from a clinical trial of a new domestic non-opioid μ1-opioid receptor agonist Tafalgin, considered a real alternative to narcotic analgesics.

Introduction. Anemia syndrome is a common disease that reduces the quality and life expectancy of cancer patients. Prevention, timely diagnosis and effective treatment of anemia are statistically significantly associated with a favorable clinical outcome of the treatment of patients, and also contributes to better tolerability of anticancer therapy.
Aim. Evaluation of the effectiveness of oral iron preparations and parenteral use of erythropoietin-alpha in patients with breast cancer and colorectal cancer, iron deficiency anemia or severe iron deficiency, immediate and long-term results of treatment, as well as the quality of life of patients with breast cancer and colorectal cancer.
Materials and methods. A retrospective analysis of the material from the Blokhin National Medical Research Center of Oncology, involved 133 patients (validation group 68 people, control group – 65 people), patients with breast cancer or colorectal cancer, suffering from anemia. Depending on the form of anemia, patients were prescribed therapy – oral iron preparations with epoetin alfa in combination or in monotherapy. The effectiveness of therapy was assessed by the rate of blood hemoglobin. Analysis and statistical processing of results using IBM SPSS Statistics 26.0. Survival analysis was carried out using the KaplanMeier method. Descriptive statistics methods are used to analyze socio-demographic and traditional patients.
Results. With a median follow-up of 61.2 months, the exclusion groups did not have significant differences in overall survival (p > 0.05). However, the group of patients with IDA who received therapy to correct the anemic syndrome and the group with FDA without adequate therapy had a greater significance in terms of 5-year OS (93.5 and 69.6%, respectively; p = 0.02). There were also no significant values for the 5-year DFS indicator (p > 0.05). However, the groups of patients with IDA who received and did not receive therapy to correct anemia probably made a big difference in terms of 5-year DFS (90.3 and 63.9%, respectively; p = 0.025). The group of patients with IDA treated with anemia to correct anemic syndrome clearly differed from the group of patients with FAD without therapy to correct anemia in terms of 5-year OS (90.3 and 43.6%, respectively; p < 0.001).
Conclusions. Carrying out antianemic therapy can significantly increase the 5-year relapse-free survival in patients with iron deficiency anemia (90.3 and 63.9%, with and without therapy, respectively; p = 0.025).

Chemotherapy-induced nausea and vomiting (CINV) is one of the most common complications of the systemic anticancer treatment. The manifestations of this complication are largely determined by subjective perceptions and individual characteristics of patients, but this complication may have unprecedented negative impact on the quality of life of cancer patients. There were significant advances in CINV prophylaxis in the recent decades, with many effective antiemetic drugs entering routine clinical practice. Current clinical guidelines for antiemetic therapy provide various possible strategies for CINV prevention, but do not give any specific guidance on the selection of individual agents within each class of emetogenic potential. NEPA, which is a fixed-dose combination of NK1-antagonist netupitant and 5-HT3 antagonist palonosteron, is the most recent antiemetic drug in clinical practice. This article reviews current data on the effectiveness of this drug and aims to define its “niche” in antiemetic therapy. The results of historical and most relevant studies demonstrating the effectiveness of NEPA in CINV prevention, pharmacological features of the drug and its potential advantages are discussed. The role of the drug in the existing therapeutic arsenal was evaluated using the example of a clinical report of treatment of a patient with an aggravated history (type 2 diabetes mellitus with poorly controlled hyperglycaemia) The patient achieved a complete response to the antiemetic therapy: no episodes of vomiting during treatment, the severity of nausea did not exceed the 1st grade, no additional prescription of antiemetic drugs was required.

Pain is an accompanied problem for many pathologic conditions and diseases. Such sensations disappear gradually when related to acute pathology or trauma. However, pain can became chronic and acquire traits of self-sustained disease. In practice, many characteristics can be useful for estimation of pain sensation, and the goal of this paper is to analyze of modern methods for intensity pain assessment in adults and children, of interpretation of pain estimation, and of possible algorithm for next steps. In majority cases, pain intensity is changing parameter. Therefore, pain assessment is performed in some standard points of time. For a quantitative assessment of pain, a scale is proposed to help the patient, relative to the extreme points of which a pointer can be placed indicating the relative severity of his sensations. For such purpose visual analog scale, numeric rating scale, and verbal numeric scale can be used. The Wong-Baker Faces Pain Rating Scale, the FLACC scale, the CRIES pain scale can be exploited in small children. In this population the CHEOPS scale, the OPS scale, and the COMFORT scale were recommended to apply after surgery. The final step of interpretation implies that quantitative data converts to ratings. The last ones form to basis of WHO analgesic ladder that is exploited for drugs selection to treat pain, in particular in patients with cancer pain or postoperative pain. From this approach, moderate and severe pain recommends to administer full opioid agonists. However, today there is a good alternative in the form of selective mu1-receptots agonist, which has lower risk of side opioid effects. Thus, in this time, there is some progress in pain management. This progress, in our opinion, is due to improved analysis of the condition of patients suffering from moderate and severe pain, and the emergence of new opioid agonists with high selectivity for the mu1 subclass of opioid receptors.

Introduction. Implementation of data from registration studies into clinical practice often presents a number of problems due to the heterogeneity of the patient population, the lack of uniformity of thinking among clinicians, and organizational difficulties. Using the example of studying the algorithm for prescribing ribociclib in a cohort of patients from one region in modern realities and the possibilities of drug provision, we have shown the main controversial points in the implementation of the results of clinical trials in the daily practice of an oncologist.
Aim. The purpose of this study was to analyze our own preliminary results of the treatment of patients with hormone-receptorpositive Her-2-negative metastatic breast cancer using ribociclib in the routine practice of prescribing CDK4/6 inhibitors outside of clinical trials, taking into account the peculiarities of regional drug supply.
Materials and methods. A retrospective analysis of the results of treatment of patients (n = 56) who took ribociclib in terms of combined hormone therapy for metastatic hormone-dependent Her-2 negative breast cancer in the practice of oncologists in the Krasnodar Territory from 2019 to 2022 was carried out.
Results. At the time of data collection and analysis, with a total follow-up time of 29 months, the median overall survival was not achieved, 52 patients (92.9%) were alive and continued to follow up. The median progression-free survival was also not reached: disease progression was recorded in 19 patients (33.9%), 37 patients (66.1%) continued treatment. A total of 14 out of 56 patients (25.1%) received ribociclib therapy in combination with drugs for endocrine therapy in the first and second lines. The best results were demonstrated by patients with a high level of expression of progesterone receptors in the tumor (p = 0.005), a low level of Ki67 proliferative activity index (p = 0.035), without metastatic visceral lesions (p = 0.034), who received the minimum number of lines of therapy before the appointment of ribociclib (p = 0.029). The results of the clinical part of the study became available due to the timely optimization of regional drug supply processes with the creation and constant monitoring by clinicians of a stable cohort of patients in the form of updated registers.
Conclusions. The introduction of the experience and knowledge of clinical oncologists into the process of drug supply management and its optimization, taking into account the understanding of data on drug efficacy and toxicity, is a promising direction and requires further discussion.

Introduction. Platinum-based chemo have long been the only option for adjuvant therapy after tumor resection in early-stage NSCLC. Osimertinib is EGFR tyrosine kinase inhibitor which demonstrated efficacy as adjuvant therapy in patients with NSCLC.
Aim. To evaluate the effects of expanding the use of osimertinib as adjuvant therapy for EGFR+ NSCLC on reducing cancer mortality in Russia.
Materials and methods. According to the ADAURA clinical trial, osimertinib has shown a significant reduction in the risk of recurrence or death, with hazard ratio of 0.17 and a 99% confidence interval of 0.11–0.26, p < 0.001. However, long-term overall survival data is not yet available in the literature. To evaluate the potential benefits of osimertinib as an adjuvant therapy for EGFR+ NSCLC, a model was proposed, which aims to describe the time to recurrence and overall survival of patients over a 10-year horizon, with or without use of osimertinib. We also evaluated the additional costs associated with expanding the use of osimertinib for this particular indication.
Results. In Russia, the use of osimertinib as an adjuvant therapy for NSCLC has the potential to benefit approximately 1 280 patients annually. Currently, around 450 patients are already receiving osimertinib as adjuvant therapy, leaving room for an additional 830 patients to be considered for this treatment option. If all eligible patients receive osimertinib, it is estimated that there could be a reduction of 683 cancer-related deaths over a span of 10 years. The long-term effects of osimertinib are particularly noteworthy, as they can positively impact the proportion of patients registered for five or more years by an increase of 0.006 percentage points, and among lung cancer patients by 0.231 percentage points. The additional costs associated with this expansion are estimated at 2.2 billion rubles per year.
Conclusions. The use of osimertinib as an adjuvant therapy for EGFR+ NSCLC has a significant and quantifiable impact on reducing cancer-related mortality in Russia.

Introduction. For the treatment of uterine body cancer (UBC), modern oncologists have at their disposal clinical recommendations of scientific communities, the set of drug options in which is represented by a limited range of drugs that have not been studied enough (phase II studies, no more than 52 patients in each). There is an obvious lack of information about clinical routine data systematization algorithms that describe the molecular biological features of the tumor, its prevalence, patient characteristics, existing treatment models, and form a decision-making program when planning the treatment of UBC patients.
Aim. Тo develop an algorithm for routing patients with UBC on the territory of the Krasnodar Region in the existing conditions for organizing medical care and human resources.
Materials and methods. Local observational retrospective study. Sources – medical records. The data were collected by the co-authors of the article in the course of daily clinical activities. Information from the medical records of 72 patients with endometrial cancer who were referred for microsatellite instability (MSI) testing at the Oncological Dispensary of Krasnodar from 01/01/2021 to 11/16/2022 was analyzed to determine the possibility of receiving immuno/immuno-targeted therapy in the second and subsequent lines medicinal treatment.
Results. In the Krasnodar Oncological Dispensary all the therapy options specified in the clinical guidelines were used. One line of systemic therapy for a common disease was received by 61 patients out of 72, only 41 patients received the second line, and only 19 patients received the third line. Five patients received the immunotargeted combination in the second line and 3 in the third. One patient received immunotherapy with pembrolizumab in the third line. One patient received immunotherapy with pembrolizumab in the third line. An analysis of the factors influencing the possibility of receiving this therapy showed the importance of timely genetic testing of MSI, as well as related organizational issues, such as the ability to quickly receive treatment and ensure appropriate follow-up of patients.
Conclusions. Based on the study, low awareness of clinicians about the possibility and necessity of early testing for the presence of MSI in an endometrial tumor was revealed. The organization of delivery of material from clinics that have a territorial remoteness, insufficient access to patient consultations by related specialists, and low patient compliance limit the introduction of modern methods of therapy for UBC patients. Establishing a system of close professional interaction between physicians will contribute to a wider introduction of new methods of diagnosis and treatment of UBC patients.

The development and introduction of cyclin-dependent kinases 4/6 (CDK4/6) inhibitors into clinical practice is one of the main achievements over the last 10 years in the treatment of metastatic breast cancer. All randomized trials demonstrated clinically significant efficacy of endocrine therapy plus CDK4/6 inhibitors in the first- and second-line therapy for hormone-dependent Her2-negative metastatic breast cancer. Three drugs are currently approved for this indication: palbociclib, ribociclib, and abemaciclib. Despite some differences in chemical, biological and pharmacological properties, as well as a range of incongruities between the patient populations enrolled in the clinical studies on the efficacy of various CDK4/6 inhibitors in the firstline therapy, all drugs showed a completely comparable improvement in progression-free survival with a hazard ratio of 0.5 regardless of previous treatments. Further traceability of the results and the accumulation of real-world clinical practice experience allowed to identify a potential difference not only in overall survival and the toxicity profiles, which are characteristic of each of the drugs, but also in the safety of use in patients of an older age group. As patients aged over 75 years are rarely enrolled in the clinical trials, the obtained results cannot be unequivocally extrapolated to this patient population, which is the decisive factor in determining the clinical experience value for an unselected patient population. The article considers clinical case reports of the use of palbociclib in the first-line therapy for hormone-dependent Her2-negative breast cancer in patients over 75 years of age with severe comorbidities.

The median overall survival for patients with metastatic triple-negative breast cancer is about 12-14 months. Chemotherapy has been the only treatment option for this tumour subtype for a long time, irrespective of immunological and genetic characteristics. Straightforward therapy algorithms have not been defined, and the optimum sequencing of chemotherapy regimens is left to the discretion of the attending physician. Today, impressive findings from clinical studies on the use of immunotherapy and targeted therapy for cancer using PARP inhibitors reflect in current guidelines, raising the chances of patients to prolong life and maintain its high quality. Thus, the use of immunotherapy as first-line treatment of PD-L1-positive tumours allowed to significantly increase the overall survival of patients for the first time in many years. And the use of PARP inhibitors in carriers of BRCA1/2 germline mutations not only significantly prolongs progression-free survival, but also improves quality of life versus standard chemotherapy regimens. The benefit is also observed in patients with an aggressive course of the disease such as damage to the visceral organs and the central nervous system. The presence of BRCA1/2 germline mutations in the genes, damage to the CNS and visceral organs is associated with an extremely unfavourable prognosis and a significant decline in life expectancy. However, a high-quality diagnosis before initiation of treatment, creating proper treatment plans and the use of modern opportunities can improve the outcomes of treatment. The article discusses possible treatment options for metastatic TNBC, reflects current guidelines on the use of immuno- and targeted therapy. A clinical case report of the treatment of a patient with a significantly aggravated history and an aggressive course of TNBC is presented. The patient with visceral metastases, brain damage and early progression after primary treatment has been receiving therapy for two years, while maintaining a satisfactory quality of life.

The syndrome of multiple endocrine neoplasia type I, MEN-1, or Wermer’s syndrome, occupies a separate place in the group of neuroendocrine tumors. Being a genetic, family-determined disease and having a transmission rate of 50%, it is manifested by multiple neoplasms of various malignant potential in many organs. Given the trend towards personalization of treatment, specialists in various fields are constantly looking for improved diagnostics and new methods of treatment. We present our own experience in the treatment of MEN-1 syndrome with somatostatin analogues. The patient, born in 1972, was observed by an endocrinologist at the age of 22, when a pituitary microadenoma was detected. After 18 years, a pancreatic tumor was detected, which was successfully removed. Histological and immunohistochemical studies verified a Grade 1 neuroendocrine tumor. Control computed tomography revealed multiple masses in the head and tail of the pancreas. Given the condition, patients since 2013 have been prescribed biotherapy with an analogue of somatostatin – octreotide. However, taking the drug was not regular, and the patient noted a deterioration in her condition. In 2019, by decision of the council, biotherapy with Lanreotide was prescribed. Even taking into account irregular examinations due to absenteeism, the control examination in 2022 showed normalization of the levels of chromogranin A and serotonin, the absence of new tumor foci and the progression of those present during Positron emission tomography. Thus, a multidisciplinary approach and the appointment of adequate therapy helps to improve the quality of life and stabilize patients with MEN-1 syndrome.

Pancreatic cancer (PaCa) is one of the most aggressive and unfavourable current oncological diseases. The vast majority of patients have unresectable or metastatic disease at diagnosis. Despite considerable achievements in the drug therapy of most malignant tumours, the immediate and long-term results of the treatment of PaCa still remain extremely unsatisfactory, as overall survival at 5 years does not exceed 10%. The high molecular genetic heterogeneity, which is characteristic of pancreatic adenocarcinomas, the low frequency of driver changes, the diagnostic difficulties, and the rapid progressive deterioration of the general health condition of most patients are just a few of the reasons for the lack of highly specific treatment. Understanding that about 10–15% of pancreatic tumours are a manifestation of genetically determined syndromes has changed the pharmaceutical treatment options for this cohort of patients. BRCA1/2 mutation carrier status is one of these reasons, while the relative risk of PaCa is 2.36 in BRCA1 mutation and 3.34 in BRCA2, respectively. The PARP inhibitor therapy experience and proven efficacy allowed to successfully use this group of drugs in the treatment of BRCA-mutated ovarian and breast cancers. The double-blind, placebo-controlled phase III POLO trial showed the benefit of olaparib as maintenance therapy in BRCA-mutated PaCa. This article presents a clinical case report of the use of olaparib in a patient with familial BRCA1-mutated metastatic PaCa.

Arsenal of a modern chemotherapist exists on a wide choice of treatment of metastatic renal cell carcinoma – the discovery of immunodrugs – checkpoint inhibitors, new multikinase inhibitors and their combinations allow choosing the optimal treatment for patients of any risk group. However, the increase in the economic burden on a medical institution, which is observed every year with the emergence of more and more indications for antitumor therapy, is a limitation for the full implementation of modern immuno-targeted regimens. Therefore, it is necessary to consider the possibility of using more affordable drug options that are optimal in their antitumor response and are not significantly inferior to the newly introduced schemes. The article presents a brief overview of the mechanism of resistance of a renal cell tumor to drug exposure, describes the evolution of drug therapy for metastatic kidney cancer before the advent of sunitinib: attempts to use various cytotoxic agents, the development of immune-mediated cytokine therapy. The results of clinical trials of sunitinib in the treatment of renal cell carcinoma, comparative studies of RECORD-3 and COMPARZ, as well as private clinical cases of the use of sunitinib in real clinical practice are described. Clinical cases show the efficacy and safety of sunitinib in the presented patients – the time without progression was 30 and 26 months, and adverse events were controlled and consistent with ongoing clinical trials: patients had hematological toxicity in the form of neutropenia, anemia, arterial hypertension, dermatological toxicity in the form of discoloration hairline and palmar-plantar syndrome. All phenomena were successfully stopped, only in the case of neutropenia, the drug was postponed until the restoration of hematological parameters. It is noted that sunitinib occupies an important place in the treatment of metastatic kidney cancer at the present time.