MEETING DATE: July 7, 2023

ITEMS ON THE AGENDA:

1. The role of the adjuvant atezolizumab plus bevacizumab in patients with hepatocellular carcinoma (HCC) at high risk of recurrence following surgical resection or ablation. Profile of the patient who will benefit the most from this therapy.

2. To evaluate the prospects for therapeutic options for patients with early HCC in Russia.

Liver cancer remains a public health concern globally, with an increasing trend in the number of incident cases worldwide. Early, precise diagnosis and timely treatment contribute to the improvement in overall and relapse-free survival. It is important that the entire arsenal of local treatments (resection, ablation and liver transplantation) can be applied in cases when HCC is detected at a very early and early stage of the disease. Tumour recurrence after surgical treatment or ablation is a complex and underexplored problem in the treatment of patients with HCC. Many factors that can predict the risk of relapse after surgical treatment have been described: tumour size >5 cm, >3 foci, micro- or macrovascular (Vp1-2) invasion, poor degree of tumour differentiation (G3-4). Our advisory board tried to identify the most important risk factors for early relapse, and to determine the role and impact of the results of the first positive clinical trial focused on the issue of early HCC, IMbrave050: a phase 3 trial of adjuvant atezolizumab + bevacizumab vs active surveillance in patients with HCC at high risk of disease recurrence following resection or ablatio.

Introduction. Non-small cell lung cancer (NSCLC) is a form of lung cancer with high incidence and low overall survival. Immunotherapy is a promising treatment method for which the selection of optimal treatment regimens for each individual patient is important.

Aim. To evaluate the effectiveness and safety of immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC.

Materials and methods. The study included 247 patients (190 men and 57 women) aged 37 to 87 years who received ICIs as monotherapy with nivolumab (n = 58; 23.4%), pembrolizumab (n = 78; 31.6%) and atezolizumab (n = 13; 5.3%), and in the form of combination chemoimmune therapy (n = 98; 39.7%). The objective response of the tumor to treatment was recorded in the presence of partial or complete regression of the tumor. The tumor response to treatment was determined in accordance with the iRECIST criteria.

Results. Objective response was achieved in 20.6% of patients, of which 13.7% were on the first line setting, and 7% of patients were on the 2nd or more line setting. Disease control was recorded in 83.3% of patients. Patients receiving combination chemoimmune therapy had a better response to treatment than those receiving monotherapy (χ² = 9.309; p = 0.020). Grade 3–4 immuno-related adverse events were observed only in 5 (2.02%) patients.

Conclusions. NSCLC immunotherapy allows to achieve high rates of objective response and disease control (20.6 and 83.3%, respectively), with a small number of grade 3–4 immuno-related adverse events (2.02% according to our data), which indicates an acceptable safety profile.

Introduction. In the structure of Russian cancer incidence, malignant neoplasms (MN) of the liver occupy 1.61%. Patients with initially unresectable hepatocellular cancer (HCC) or progressive HCC after local treatment methods, in the absence of contraindications, are subject to systemic therapy.

Aim. To evaluate the direct effectiveness and long-term results of treatment of patients with inoperable HCC with the combination of atezolizumab and bevacizumab in real clinical practice.

Materials and methods. A multicenter (7 centers) retrospective observational study was conducted. It includes 56 previously untreated patients and 12 pretreated patients with a confirmed diagnosis of HCC who were treated with atezolizumab and bevacizumab. The male to female ratio was 2:1, with an average age of 60 years. ECOG 0-1 was in 86.8%, Child-Pugh liver function A – in 76.5%, B – in 23.5%, macroscopic portal vein invasion – in 27.9%, extrahepatic spread – in 35.3%, AFP more than 400 IU/ml – in 38.2%.

Results. Use of the atezolizumab and bevacizumab regimen as a first line led to a partial response in 7 patients (12.5%), to stabilization in 39 (69.6%), to progression in 10 (17.9%). The disease control rate was 82.1%, median progression free survival (PFS) was 9.9 months (95% confidence interval (CI) 6.2-n/a). Median overall survival (OS) was not reached (95% CI 10.2-n/a). PFS was significantly influenced by the functional state of the liver according to the Child-Pugh scale. Median PFS in class A was 18.0 months, in class B – 5.6 months: HR 2.54; 95% CI 0.92–7.05; p = 0.03.

Conclusion. The atezolizumab and bevacizumab regimen in real clinical practice demonstrates tolerability of therapy and treatment results that are not inferior to the data obtained in the registration study. No new adverse events were identified.

Cervical cancer (CC) remains one of the common tumour diseases of women. It accounts for 9.8% of all neoplasia in women. The Food and Drug Administration approved pembrolizumab with PD-1 inhibitor antibodies for the treatment of RSM following the KEYNOTE-158 clinical trial. PD-L1/PD-1 inhibitors have shown promising results against objective response rate in female patients with CC. A clinical case of pembrolizumab treatment of a patient with metastatic CC with progression after radiotherapy and pelvic organ evisceration is described. The patient underwent IHC examination of the tumour material and was found to have PDL1 expression of more than 1% according to the 22C3 antibody assay. According to the instructions for Pembroria® it was decided to start systemic chemotherapy in the regimen of paclitaxel 175 mg/m², carboplatin AUC5 and pembrolizumab at a dose of 200 mg every three weeks. After the third course, a control MRI study was performed. A partial response according to iRECIST criteria was confirmed. After the sixth course of therapy cytostatics were cancelled, the patient continued monotherapy with pembrolizumab 200 mg once every three weeks. At the control MRI after 10 months of therapy, the tumour conglomerate in the right hindbrain fossa was not detected and a complete response was confirmed. In the given observation anti-PD1 therapy and metastatic CC allowed to achieve complete remission of the disease. Thus, the clinical observation demonstrates the efficacy of pembrolizumab therapy in patients with advanced CC.

The possibilities in the treatment of patients with non–small cell lung cancer are constantly expanding – thanks to high-performance genomic profiling methods, we are discovering new targets in the tumor for drug action, as a result, new targeted drugs appear, some of them have several application points. Multipurpose drugs have a number of advantages and therefore have become the main direction of drug development. Entrectinib is an oral low molecular weight multikinase inhibitor that blocks three targets at once – the receptors of tyrosine kinases ROS1, NTRK1/2/3 and ALK, in 2023 was approved by the Ministry of Health of the Russian Federation for the treatment of adult patients with ROS1-positive metastatic non-small cell lung cancer. This form of lung cancer is classified as a rare orphan disease, which usually occurs in younger people (about 50 years old), more often in women and non-smokers. Until recently , we had the only active targeted drug – crizotinib. It provided a sufficiently high immediate effect and long-term control of the disease. However, his intracranial activity was not evaluated prospectively, and a retrospective analysis showed modest results. Entrectinib is distinguished from its competitor by high intracranial activity, and, as is known, metastatic brain damage in patients with activating mutations is quite common. With comparable indicators of objective response, its duration and time to progression, entrectinib provides a high level of intracranial control and reduces the risks of progression in the central nervous system in patients who did not have brain metastases at the beginning of therapy. In addition, entrectinib demonstrates good tolerability.

The incidence of hepatocellular carcinoma (HCC) in Russia and worldwide is steadily increasing over time. The majority of HCC patients are diagnosed at a late stage of the disease, which is not suitable for potentially curative treatment methods. Before the emergence of new treatment regimens, the median overall survival for this condition was just over one year. Studying combinations of immunotherapy and targeted therapy has improved clinical outcomes compared to monotherapy with tyrosine kinase inhibitors, but the new treatment regimens cannot be prescribed to all patients with advanced HCC. The combination of atezolizumab with bevacizumab may be prescribed to eligible patients with advanced hepatocellular carcinoma who do not have varicose veins and have no history of hypertensive crises. In real clinical practice, it is extremely difficult to select patients who meet the inclusion criteria for clinical trials. Monotherapy with tyrosine kinase inhibitors is also effective regardless of the etiology of HCC development and can be prescribed to patients with signs of liver insufficiency (Child-Pugh B) as opposed to combined therapy. Double immunotherapy has shown its efficacy in second-line treatment, and in the future, these combinations may also demonstrate their effectiveness in first-line treatment of hepatocellular carcinoma. There is insufficient evidence on the effectiveness of immunotherapy in patients awaiting liver transplantation. For this category of patients, the drugs of choice are lenvatinib and sorafenib. The article highlights the specific considerations in choosing the treatment regimen based on the etiology of the disease, treatment goals, concomitant patient conditions, and the presence/severity of liver insufficiency.

Non-small cell lung cancer (NSCLC) that occupies a leading place in the pattern of cancer incidence and mortality is a highly heterogeneous group of diseases. The presence of a wide spectrum of NSCLC driver mutations has led to a fundamentally different understanding of the treatment strategy for this cohort of patients and a significant improvement in long-term oncological outcomes, even in the metastatic process. Chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene loci on chromosome 2 are found in approximately 3–5% of patients with metastatic NSCLC (mNSCLC) and in most cases are associated not only with a number of specific clinical features, but also with high sensitivity to targeted therapy with tyrosine kinase inhibitors (TKI). Crizotinib was the first approved ALK inhibitor, but although most patients achieved response within the first two years after start of the treatment, disease progression occurred often due to intracranial injury. The development of second-(ceritinib, alectinib), brigatinib and third-generation (lorlatinib) drugs has led to a statistically significant improvement in progression-free survival (PFS) rates, as well as control over intracranial manifestations of the disease and a change in the initial treatment strategy for these patients. In addition, new-generations of TKIs were developed to solve the problem of acquired resistance, as well as to achieve the best outcomes in the presence of such unfavourable factors as the presence of a TP53 mutation and/or ALK inhibitor low-sensitive translocation variants of the intracellular kinase domain of EML4 (echinoderm microtubule‐associated protein‐like 4)‐ALK (anaplastic lymphoma kinase) protein. Thus, advances in the therapeutic options for ALK-positive mNSCLC has completely changed the course of the disease, resulting in a significant increase in overall survival (OS) rates not only with the sequential use of different generation TKIs, but also with the choice of the most effective first-line option. In this article, we present an analysis of data on the efficacy and toxicity of lorlatinib, a third-generation TKI, in the first-line treatment for ALK+ mNSCLC.

Current clinical guidelines of various domestic and foreign professional communities indicate combination regimens as an option for the first-line therapy for metastatic сlear cell renal cell carcinoma, regardless of the patient’s prognosis group. This review article is devoted to the analysis of the current evidence base for the use of different variants of combination therapy regimens in patients with metastatic renal cell carcinoma and assessment of the role of single-component cancer therapy options in the initial treatment of this disease. We reviewed the results of studies of current immuno-oncology therapy regimens in the first-line renal cell carcinoma therapy with a focus on a favourable prognosis group, taking into account the latest updates from the studies evaluating the efficacy of combination treatments (pembrolizumab/axitinib, pembrolizumab/lenvatinib, nivolumab/cabozantinib, avelumab/axitinib). We found that although the use of certain combinations of immunooncology and targeted drugs give better results of disease control, objective response and progression-free survival rates, none of the studied combinations to date has shown a significant increase in overall patient survival rates, which is a key treatment efficacy indicator in metastatic cancer. Conclusions drawn from this review indicate that monotherapy with tyrosine kinase inhibitors, such as sunitinib or pazopanib, appears to be sufficient and optimal from a clinical and economic point of view in the treatment of a favourable prognosis group. For patients with a favourable prognosis, tyrosine kinase inhibitor monotherapy may be a primary rather than an alternative therapeutic option until the benefit of combinations in terms of overall survival rates has been showed.

More than 25 years ago, the discovery of imatinib, the first ATP-competitive inhibitor of BCR::ABL1, the driving oncoprotein of chronic myeloid leukemia, revolutionized patients life by transforming a fatal condition into a chronic disease. The review analyzes data on the effectiveness of chronic myeloid leukemia therapy with tyrosine kinase inhibitors and a number of provisions that require discussion and, possibly, revision at the present stage. The first clinical trials of imatinib, the first ATP- competitive inhibitor of BCR::ABL1, started in 1998, demonstrated extremely high therapeutic efficacy, impressively increasing the rates of relapse-free and overall survival in patients with chronic myeloid leukemia. The life expectancy of the overwhelming number of patients has become comparable to the life expectancy of the main population. Over the years, the arsenal of therapeutic agents for the treatment of chronic myeloid leukemia has been significantly enriched: three ATP-competitive tyrosine kinase inhibitors of the 2^nd generation have been created and approved for use, 2 drugs of the 3^rd generation: ponatinib, and the first allosteric tyrosine kinase inhibitor asciminib have been registered for the treatment of patients with the T315I mutation. Regular cytogenetic and molecular genetic monitoring makes it possible to adequately assess the volume of the leukemic clone and is an integral part of evaluating the effectiveness of therapy, allowing to control and maintain remission in a number of patients without the use of tyrosine kinase inhibitors. Today imatinib remains the key drug of the 1^st line of therapy, at the same time, the appointment of 2^nd generation tyrosine kinase inhibitors in the first line of therapy can lead to an earlier and deeper response. The choice of the drug for each individual patient, taking into account the best tolerability and maximum effectiveness, allows individualizing treatment and expanding the possibilities of therapy.

Introduction. The development and study of new enteral nutrition (EN) formulas is a major challenge to modern practical medicine. The creation of enteral nutrition products, which in addition to their intrinsic nutritional properties have detoxifying properties, will contribute to enhanced clinical efficacy and more active recovery of patients.

Aim. To conduct a comparative pharmaco-economic analysis of the effectiveness of using new domestic products for enteral nutrition produced by LEOVIT Nutrio (Russia), which have detoxifying activity, and products from other manufacturers.

Materials and methods. The studies were carried out using standard cost-effectiveness analysis techniques. A comparative analysis of following products:Nutrien Standard (JSC Infaprim, Russia), Supportan drink (FreseniusKabi, Germany), Nutridrink compact protein (Nutricia, Holland) and Peptamen (Nestle, Switzerland), Detoxifying Protein Cocktail, Restoring Protein Cocktail and Detoxifying Drink (LEOVIT Nutrio LLC, Russia).

Results and discussion. Calculations for all analyzed economic parameters showed the advantages of using new domestic products for enteral nutrition. It was found that the total direct costs for enteral nutrition in the group of cancer patients who additionally took a detoxification cocktail were the smallest and amounted to 3332.0 rub, the increase in blood protein concentration over 14 days of therapy was 11.1 g/l, and for albumin over the indicated period is 6.7 g/l. Compared to products from other manufacturers, the lowest cost in relation to the achieved effect (CER) was observed when using a restorative cocktail – 305.69 rub. for protein and 512.62 rub. by albumin. The total direct costs for enteral nutrition in the group of patients who took the Detoxification Drink in comparison with other products on the Russian market were also the lowest and amounted to 840.00 rubles.

Conclusions. The authors concluded that there are significant economic advantages of using the new domestic enteral nutrition LEOVIT compared to other products and consider them as the product of choice when providing enteral protein nutrition to patients with various diseases accompanied by intoxication of the organism.

Introduction. Malnutrition of cancer patients is a big problem today. This is especially evident in patients with tumors of the gastrointestinal tract, where the frequency of this condition reaches high values. Malnutrition has a direct negative impact on the tolerability of treatment, long-term results and quality of life of this category of patients, so it is important to identify this condition and, if possible, correct it.

Aim. To evaluate the effect of protein nutritional support on blood counts, prolongation of intervals between chemotherapy courses, postoperative complications, progression-free life expectancy and OS in patients with gastric cancer after surgical treatment and during adjuvant chemotherapy.

Materials and methods. The study included 106 patients with gastric cancer who received surgical treatment followed by postoperative chemotherapy according to the XELOX regimen. The patients were divided into 2 groups: in the first group, patients received additional protein nutrition (Nutridrink Compact Protein) both before and after surgical treatment, and during chemotherapy; in the second group, patients did not receive nutritional support – the control group.

Results. Median levels of leukocytes, neutrophils and platelets during treatment were higher in group 1. Surgical complications in the group with nutritional support occurred significantly less frequently than in the control group, the same applies to complications after chemotherapy. During treatment, lengthening of the intervals between courses occurred statistically significantly more often in group 2 (without protein nutrition). 4-year overall survival was statistically higher in the protein diet group. The median PFS in patients from the first group was higher and amounted to 55.6 months, in the second group – 46.7 months.

Conclusion. The presence of additional protein nutrition is an independent factor in the prognosis of the disease, since it significantly increases both relapse-free and overall survival of patients.

Despite remarkable progress in the management of pediatric oncological diseases they remain one of the leading causes of mortality. The disease progression due to tumor resistance, treatment-induced toxic effects and infections complications may contribute to the lethality. New diagnostic technologies facilitate the identification of clinically significant genetic alterations for individualization of therapy approach in order to increase its effectiveness, reduce associated toxicity and improve quality of life of patients and their families. The most promising diagnostic approach is based on next-generation sequencing and includes targeted-, whole exome- and genome sequencing of patients’ blood DNA and tumor tissue. Despite the low rate of detected pathogenic alterations, some of them have prognostic significance, determine sensitivity to anticancer agents and targeted therapy. Moreover, targeted therapy in some cancer types shows benefit over standard therapeutic options. The application of targeted therapy in pediatric patients poses more challenges than in adults. This is due to the absence of established doses, regimens and indications for targeted agents in pediatric clinical trials, risks of associated toxicity and its high cost. This paper summarizes the data on molecular genetic markers, which are potentially helpful in guiding therapy for cancer in children.

Introduction. The standard initial treatment for patients with hormone receptor positive, HER2 negative, metastatic breast cancer (HR+/HER2– mBC) involves the use of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy. The combination therapy has proven effectiveness in numerous Phase II and III randomized controlled trials (RCTs). Nonetheless, RCTs may not fully represent real-world clinical situations due to their stringent inclusion criteria, resulting in a specific patient population.

Aim. Analyze of ribociclib using for treating patients with HR+/HER2– advanced breast cancer (mBC) at the Republican Clinical Oncology Dispensary.

Materials and methods. Patients diagnosed with HR+/HER2– mBC who were treated in clinical routine with ribociclib in combination with different endocrine agents between 2016 and 2020 were identified and enrolled in this retrospective study. Clinicopathological characteristics and clinical outcomes were recorded with particular emphasis on ribociclib therapy course (progression-free survival (PFS), toxicity, dose reduction).

Results. Data from n = 101 patients were evaluated. The mean patient age was 61 years. The study included 67 (66.3%) patients with progression after radical treatment and 34 (33.7%) patients with primary disseminated breast cancer. Dose reduction due to adverse events was performed in n = 14 cases (13.9%). Presence of prior therapy lines and lower ECOG status were associated with shorter PFS, whereas estrogen positivity and the choice of fulvestrant over aromatase inhibitor were positively associated with PFS. Metastatic pattern, progesterone positivity and dose reduction due to toxicity did not significantly impact on PFS.

Conclusion. Our real-world data analysis on ribociclib treatment in Russian regional hospital supports data from RCTs regarding both treatment efficacy and safety of CDK4/6i for treatment of patients with HR+/HER2– mBC. Currently, by expanding our experience with CDK4/6 inhibitors in different groups of patients with mBC, we will be able to provide patients with optimal treatment options.

Introduction. Multiple myeloma (MM) accounts for 1% of all cancers and about 10% of all hematological malignancies. Although there are many types of current therapeutic approaches, MM still remains an incurable disease, which points to the need for improvement of the management of patients with this disease in real-world clinical settings.

Aim. To analyze the actual practice of treating Russian patients with multiple myeloma (MM).

Materials and methods. A multicenter observational retrospective study was conducted. The final analysis included data from 268 patients with the diagnosis code C 90.0, C90.1, C 90.2, C 90.3 ICD-10, aged ≥ 18 years, treated and monitored in 3 Russian centers.

Results. 31.7% of patients had bone and/or extramedullary plasmacytomas. According to Durie Salmon, there were patients with stage III (56.1%) prevailed in ISS - with stage II (41.8%). Cytogenetic studies were performed only in 5.2% of patients. Patients most often encountered diseases of the cardiovascular system (43.3%), kidneys (14.7%), endocrine system (13.1%). The average number of days of hospitalization is about 41.9 days per calendar year. In the first line, 90% of patients received bortezomib-based regimens, 15.8% received high-dose chemotherapy with autologous hematopoietic stem cell transplantation. 66.7% of first-line patients responded to treatment. In the 2nd line, the most commonly prescribed regimen was Rd (lenalidomide with dexamethasone (26.83%), bortezomib-based regimens (24.39%), regimens with the inclusion of new agents (daratumumab, ixazomib, carfilzomib) (17.07%) 40.82% patients responded to treatment.Three-line regimens were dominated by chemotherapy (29.73%) and with the inclusion of new agents (daratumumab, pomalidomide, carfilzomib) (27.03%), 39.3% responded to treatment.

Conclusion. Optimization of therapy for patients with MM and the need to improve approaches to the treatment of this disease remains a significant problem in the modern healthcare system. The results of the management and treatment of patients in real practice is of decisive importance for the choice of the most effective methods of therapy.

Introduction. Melanoma is an aggressive form of skin cancer caused by the transformation of melanocytes into malignant cells. Currently, immunotherapy is one of the most promising treatment methods, but searching the most optimal treatment regimens is still ongoing.

Objective. To evaluate the effectiveness and safety of the use of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma.

Materials and methods. The study included 229 patients (114 men and 115 women) aged 21 to 91 years who received (ICIs) as nivolumab (n = 168; 73,4%) and pembrolizumab (n = 30; 13,1%) monotherapy, and combination of nivolumab and ipilimumab (n = 31; 13,5%). The objective response of the tumor to treatment was recorded in the presence of partial or complete regression of the tumor. The tumor response to treatment was determined in accordance with the iRECIST criteria.

Results. Complete regression was observed in 16.7, 15.9 and 8,7% of patients, partial – in 11.1, 11.4 and 17.4%, stabilization was detected in 51.2, 50.0 and 34.8% and progression – in 21.0, 22.7 and 39.1% of patients with first, second and third and more-line setting, respectively. The median response time was 3.14, 5.18 and 3.63 months, the median response duration was 16.21, 8.96 and 30.15 months in first, second and third and more-line setting, respectively. Grade 3–4 immuno-related adverse events (irAEs) were observed in 8 (3.5%) patients.

Conclusions. Immunotherapy of metastatic melanoma allows achieving high rates of objective response and disease control (27.5 and 76.9%, respectively). This method of treatment is characterized by an insignificant amount of grade 3–4 irAEs (3.5% according to our data), which indicates an acceptable safety profile.

Introduction. Despite the registered standard treatment option for patients who underwent radical resection for metachronous metastases of colorectal cancer (CRC), the feasibility of adjuvant chemotherapy (ACT) for all patients seems controversial. Due to studies demonstrating improved disease-free survival rates with postoperative chemotherapy vs observation, it would seem that there is reasonable expectation of improved overall survival (OS) rates, which, however, were not statistically different between groups. This article presents the interim results of our own study.

Aim. To analyse the efficacy of ACT vs dynamic observation in patients who underwent surgery for metachronous metastases of colorectal cancer.

Materials and methods. It was a prospective-retrospective, non-randomized, non-inferiority study. A total of 120 patients were recruited between June 2008 and September 2022. The ACT group included 71 patients. All patients received only oxaliplatin-based chemotherapy regimens; the dynamic observation group included 49 patients.

Results. The interim analysis showed that the median disease-free survival (mDFS) in the ACT group (n = 71) was 20.9 months (13.7–28.3) vs 24.4 months in the dynamic observation group (n = 49) (11.1–37.7), HR: 0.76 (95% CI: 0.45–1.29), p = 0.29. Two-year disease-free survival (DFS) rates were 46.6% in the post-surgery chemotherapy (CT) group (n = 50) and 55.5% in the experimental group (n = 31), HR: 0.69 (95% CI: 0.39–1.2), p = 0.21.

Conclusion. ACT has not improved the long-term treatment outcomes in patients who underwent radical resection for metachronous metastases of CRC.

At least 25% of the anticancer drugs are intended for oral use, while the creation and rapid introduction of oral drugs into clinical practice is constantly growing. Between 2006 and 2021, 80 oral forms of anticancer drugs were approved. It has been shown that patients prefer oral therapy to intravenous therapy if such a replacement is possible with equal efficacy and toxicity of the drugs. This once again emphasizes that the issue of adherence to treatment with oral forms is open and relevant for study. Currently, adherence, as the main factor in achieving the best clinical outcome, has been studied from different perspectives. However, there are no structured data globally, and, accordingly, evidence-based and specific recommendations in the absence of adherence. The review includes data from studies performed over the past 10 years, studying the adherence of patients to treatment with oral anticancer drugs. The data sources for the review were the Medline, Embase, and Scopus databases. Literature analysis showed that the most important aspects in the field of adherence to treatment with oral anticancer drugs include the level of patient adherence to treatment, factors affecting non-compliance, correlation of treatment adherence and clinical outcomes in malignant neoplasms. At the same time, the article considers the impact of non-compliance on the health care system as a whole. The most reliable and up-to-date data in the study area were examined to subsequently identify measures aimed at achieving the best practice in the organization of healthcare for patients with malignant neoplasms. The research results demonstrate the variability and heterogeneity of data, the lack of unified methodological approaches. In turn, this prevents the formation of objective and reliable conclusions about adherence. To make rational strategic decisions on monitoring adherence to treatment, it is necessary to initiate large-scale studies, adopt uniform standard procedures and recommendations for assessing adherence.

Malignant biliary tract tumors are highly aggressive, with a 5-year survival rate in advanced disease 2–7%. During last decade therapeutic options for treatment biliary cancer were extremely limited. The unchanged standard of first-line therapy since 2010, based on ABC-02 trial, has been GemCis combination. The TOPAZ-1 phase III trial for the first time for last 12 years reported a survival benefit with the antiprogrammed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer, achieving a median survival of 12.9 months (11.6–14.1) compared to 11.3 months (10.1–12.5) in the placebo group (RR 0.76 [0.64–0.91]). The objective response rate was 26.7% in the durvaulmab group compared with 18.7% in the placebo group. Median of overall survival is highly dependent on the best antitumor response achieved, with patients in the durvalumab group with a partial/complete response having a median survival of 19.5 months (95% CI: 15.7–28.3), with stable disease 13.6 months (95% CI: 12.2–14.7), and with progression disease 5.7 months (95% CI: 3.6–8.9). This article describes the features of the tumor microenvironment and immunogenicity of cholangiocarcinomas, provides studies of the early phases of immunotherapy with durvalumab and tremelimumabm, and provides a detailed analysis of the key study TOPAZ-1. In addition, we describe a clinical case that demonstrates long-term disease of advanced cholagiocarcinoma due to impact of significant advances in the modern treatment of cholangiocarcinoma with the introduction of immunotherapy with durvalumab, targeted therapy and the use of a new technique of local radioembolization.

Cutaneous melanoma is the most common tumor that metastasizes to the gastrointestinal tract, however, the diagnosis of visceral metastases remains difficult due to its low symptoms. Lifetime verification of melanoma metastases in the digestive tract is only 1–4%. Additional difficulties in verifying visceral melanoma metastases arise due to spontaneous regression of the primary tumor. The presented rare clinical case illustrates a variant of the course of disseminated melanoma of the skin with metastatic lesions of the gastrointestinal tract, while the dissemination was preceded by spontaneous regression of melanoma of the skin. Despite the lifetime endoscopic verification of multiple visceral metastases of cutaneous myeloma, the patient’s prognosis is unfavorable. The fact of spontaneous regression of cutaneous melanoma influenced the late diagnosis of melanoma dissemination, also due to the rarity of melanoma metastasis in the mucosa of the upper digestive tract, endoscopists are not sufficiently aware of endoscopic variants of melanoma metastases. It should be noted that endoscopic diagnostic methods must necessarily be included in the examination plan of a patient with melanoma, and when dynamically monitoring patients with melanoma after treatment, it is necessary to pay attention to non-specific signs of gastrointestinal tract damage (abdominal pain, anemia). In addition, in a patient with a history of melanoma, with endoscopic detection of an unpigmented neoplasm, it should be differentiated with a possible metastatic lesion, histological and immunohistochemical examination of the biopsy should be performed.

Colorectal cancer is one of the most common malignancies in the general population and has many histological subtypes. Signet-ring cell adenocarcinoma is a rather rare variant of this pathology. It is characterized by molecular genetic and morphological features that are absent in classical adenocarcinomas, which causes some nuances in the clinical course and approach to therapy of this type of tumor. In our clinical case, a 68-year-old patient went to a general practitioner with complaints of abdominal pain, changes in the act of defecation, and according to the primary physical and instrumental examination, he was diagnosed with chronic distal colitis, and later he was prescribed anti-inflammatory therapy. However, six months later, the patient went to the doctor again with complaints of worsening condition and symptoms, after examination, he was diagnosed with adenocarcinoma of the sigmoid colon, but due to low adherence to treatment, as well as late diagnosis, the patient died within six months. Surgical treatment of the patient was limited to resection of the sigmoid colon due to peritoneal adhesions. In the postoperative period, the development of fibrinous-purulent peritonitis and increasing cardiovascular failure were clinically noted. At autopsy, the histological variant of the lesion was changed to the signet-ring cell form with metastasis to the liver and greater omentum. Death occurred from disseminated intravascular coagulation syndrome with the development of acute renal failure and centrilobular necrosis of the liver. Clinical observation emphasizes the importance of introducing modern molecular diagnostic methods into wide practice.

Over the past two decades, the medical community around the world has been not only a witness, but an active participant in the global transformation of healthcare taking place against the backdrop of the rapid development of modern biomedical technologies. Of course, within the framework of these transformations, several quite independent directions can be distinguished. However, most of them, one way or another, can be united by the concept of “personalized medicine”, which is the subject of discussion among doctors of all specialties, which emphasizes its undoubted relevance. One of the clearest confirmations of this is the rapid growth in the number of review publications devoted to the consideration of issues of a personalized approach in medicine. Using the example of one of the most unpredictable tumors – skin melanoma – in recent years, expressive data have been obtained indicating the effectiveness of individual approaches, personalization of treatment as a result of the use of timely, gene-molecular studies. Despite the fact that in most cases melanoma is localized on the skin and, with a certain degree of oncological alertness, can be detected in the early stages, statistics indicate disappointing facts about the advanced state of the disease. Over the past 40 years, the incidence has increased by 300%. The possibilities of targeted and immunotherapy in the treatment of melanoma in patients with an advanced and unresectable stage of the disease allow long-term effective control of the disease and its symptoms.