Lung cancer is one of the most common malignant tumors with the highest mortality, with about 85% of cases of the disease being non-small cell lung cancer. To date, adjuvant chemotherapy based on platinum preparations remains the standard of treatment for patients with radically operated stage II or III non-small cell lung cancer. However, a large proportion of patients still have a risk of developing a recurrence of lung cancer even after complete resection of the tumor. That is why there is a need to search for new methods of treatment of early stages of NSCLC, which will minimize the likelihood of postoperative relapses and improve survival in a potentially curable group of patients. Already today, clinical trials are beginning to advance the treatment of non-small cell lung cancer in the early stages beyond the standard cytotoxic chemotherapy. Immunotherapy, represented by immune checkpoint inhibitors, is being investigated in an increasing number of clinical trials in patients with operable NSCLC at early stages, gradually enriching existing treatment methods. At the same time, some issues related to adjuvant immunotherapy have yet to be considered. The choice of the drug, the use of monotherapy or combined treatment regimens remain unclear. This review examines the progress of research aimed at improving adjuvant therapy through the inclusion of immune checkpoint inhibitors in the treatment of early stages of resectable non-small cell lung cancer. Adjuvant immunotherapy can improve relapse-free survival in individual patients with resectable lung cancer, and current or planned studies using biomarkers and immunotherapy may also ultimately lead to an improvement in the overall survival of this group of patients.

Indications  to immunotherapy in cancer treatment continue to expand, thus there are more and more questions about clinical aspects of using different checkpoint inhibitors. Despite similar mechanism of action between widely used antibodies to PD-1 (nivolumab, pembrolizumab, prolgolimab) and PD-L1 (durvalumab, avelumab, atezolizumab), inhibitors are different due to features of monoclonal antibodies structure they are based on. For instance, toxicity leading to discontinuation of treatment occurs more frequently with anti-PD-L1 drugs than PD-1 inhibitors. On the contrary, the average incidence of any grade IRAEs was higher in patients treated with anti-PD-1 drugs. The revealed differences in the toxicity of the analyzed groups of drugs could be associated with the type of action of the drug. The feature of the PD-L1 inhibitors is more frequent occurrence of antibody-dependent cellular cytotoxicity reactions. However, PD-1 inhibitors  showed a statistically significant survival benefit, according to a meta-analysis comparing anti-PD-1 and anti-PD-L1 groups. Besides data on differences in the efficacy and toxicity profiles of these agents, in this article we also analyze different issues in the structure of drug molecules, in particular, the role of LALA mutation in anti-PD-1 inhibitors. Understanding the key distinctive points of check-point inhibitors  (CPI) in the future may allow  to solve the problem of rechallenge  and reintroduction after management of severe IRAEs.

Hepatocellular carcinoma is a common type of liver malignancy and one of the leading causes of cancer death worldwide. In the Russian Federation, according to statistical reports, there is also an increase in the incidence. For over 10 years, the tyrosine kinase inhibitor sorafenib has been the only approved treatment for advanced hepatocellular carcinoma. Lenvatinib was registered as the second drug for the treatment of advanced hepatocellular carcinoma in the first line. In the era of checkpoint inhibitors, the possibility of such therapy in the first and subsequent lines of advanced hepatocellular carcinoma remains relevant. The combination of atezolizumab with bevacizumab in a phase III study (IMbrave150) improved treatment outcomes such as overall survival and progression-free survival. The results of the phase III randomized trial IMbrave 150 showed undoubtedly better efficacy of the atezolizumab + bevacizumab combination compared to sorafenib in terms of a median progression-free survival of 6.8 vs 4.3 months. The above clinical observation demonstrates the result of treatment of a patient with advanced hepatocellular carcinoma with a combination of atezolizumab and bevacizumab. After verification of the diagnosis, since January 2021, therapy with a combination of atezolizumab 1200 mg, bevacizumab 15 mg/kg was started with an interval of 21 days.

At present, 20 courses of therapy have been carried out in this regimen, and the stabilization of the disease is maintained. Against the background of the ongoing therapy, no adverse events were noted, including immune-mediated ones that required the abolition or reduction of doses of drugs. In the above clinical observation, a patient with severe comorbidity achieved stabilization of the disease in the first three months of therapy. Combination therapy showed a favorable tolerability profile.

Introduction. Cyclin-dependent kinase 4/6 inhibitors are indicated in endocrine therapy for the treatment of hormone receptorpositive, HER2-negative, advanced, or metastatic breast cancer. In the recent past, abemaciclib made its debut as a combinatorial partner for adjuvant therapy in hormone-dependent breast cancer. This article demonstrates the analysis of our own experience of introducing abemaciclib into clinical practice.

Aim. The aim of the study was to evaluate the preliminary results of treatment of patients with hormone receptor-positive HER2-negative metastatic breast cancer using abemaciclib outside the framework of clinical trials, in the real clinical practice of an oncological dispensary.

Materials and methods. A retrospective analysis of the results of treatment was carried out in 27 patients who were prescribed abe-maciclib in various regimens and lines from April 2021 to January 2022 in the conditions of routine practice in the Krasnodar region.

Results and discussion. Analysis of the total population of 27 patients at a median follow-up of 8 months showed that the median PFS was not reached. The one-year PFS was 68.8%. Treatment outcomes were independent of prescribing abemaciclib to treat baseline metastatic disease or breast cancer progression after previous radical treatment (p = 0.60). The PFS did not depend on the expression of progesterone receptors in the tumor tissue (p = 0.326) and the proliferative activity index Ki-67 (p = 0.618). Patients who received no more than 2 lines of previous drug treatment for a history of metastatic breast cancer had the greatest benefit from abemaciclib therapy (p = 0.001).

Conclusions. Despite a relatively difficult group of patients (96% of patients with visceral metastases), abemaciclib has demonstrated efficacy and safety. The effectiveness did not depend on the analyzed factors: Ki-67, the level of expression of progesterone receptors, the type of metastatic disease (de novo metastatic or progressive breast cancer). In view of the best results, it is advisable to prescribe abemaciclib in the early lines of therapy.

The Advisory Board was held on December 24, 2021. The molecular genetic research lead specialists and national lead oncologists discussed issues of diagnosis of NTRK gene translocations in patients with non-small cell lung cancer (NSCLC), as well as current opportunities for the treatment of patients with NSCLC caused by NTRK gene fusions. The experts reaffirmed the necessity to identify timely patients with NSCLC caused by NTRK gene fusions, as the correct diagnosis of the disease, including the use of modern diagnostic methods of NTRK gene fusion (NGS is the most sensitive and specific method) determines the success of patient treatment. In this regard, it is critical that physicians know the advantages and disadvantages of each molecular diagnostic method used to have the opportunity to choose the best approach in each clinical case. In order to have a clear, well-functioning strategy for managing patients with suspected NSCLC caused by NTRK gene fusion, it is necessary to use molecular genetic tests, as well as include TRK inhibitors (in particular, the drug larotrectinib; at the time publication of the Resolution, the drug larotrectinib is not registered in the territory of the Russian Federation) in the clinical guidelines for the treatment of lung cancer. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor. The clinical studies on larotrectinib have demonstrated high response rates and durable responses in adults and children with tumours associated with NTRK gene fusions, including primary CNS tumours and brain metastases. The objective response rate observed with larotrectinib was 79%, with 16% achieving a complete response and 64% achieving a partial response. At the same time, the median progression-free survival on larotrectinib was 28.3 months, and the median overall survival was 44.4 months.

Before the development and implementation of the first PI3K inhibitor (alpelisib), the presence of a mutation in the PIK3CA gene had only prognostic value: it determined the unfavorable course of luminal HER2-negative metastatic breast cancer (testing for mutations was not part of routine screening methods). Achievements in the treatment of HR+HER2- mBC are primarily associated with the use of CDK4/6 inhibitors, which allowed not only a significant increase in the median progression-free survival while maintaining high quality of life, but also significantly increased overall survival of patients with luminal HER2-negative metastatic breast cancer. However, subgroup analyses demonstrate that the presence of the PIK3CA mutation is an independent factor in decreasing progression-free time and overall survival, even in patients treated with CDK4/6 inhibitors. Mutations of the PIK3CA gene are diagnosed in 30-40% of luminal metastatic breast cancer patients, they are associated with an increased risk of relapse and disease progression, are associated with a significant reduction in survival rates and treatment effectiveness, and determine the development of primary and secondary resistance to endocrine therapy. Standard endocrine therapy with fulvestrant combined with alpelisib has significantly improved treatment outcomes in patients with HR+HER2-metastatic breast cancer with the PIK3CA mutation who previously received treatment for advanced disease or had progression during adjuvant therapy. This combination is now included in all major international guidelines and is a priority therapy option. Testing for PIK3CA mutations is the current diagnostic standard in luminal HER2-negative mBC. The review presents an update of the main clinical trials with alpelisib, treatment results from real clinical practice, and also considers aspects of use in pretreated patients with different medical history. The article outlines the main recommendations for the prevention and correction of adverse events, and presents our own experience of using alpelisib in a patient with a classic course of breast cancer with a PIK3CA mutation.

In recent years, significant advances have been made in systemic therapy for patients with metastatic melanoma of the skin, resulting in an increase in one-year overall survival (OS) from 25 to 85% and 5-year OS from less than 10 to 60% in certain patient subgroups. Approximately 50% of patients with metastatic skin melanoma are diagnosed with metastatic brain lesions in the course of the disease. Modern drug therapy for metastatic brain lesions is slowly but surely proving to be effective. Thus, in the presence of a mutation in the BRAF gene, BRAF inhibitor monotherapy provides an intracranial objective response rate (iORR) of 25 to 40%, whereas BRAFi + MEKi combined targeted therapy (CTT) achieves already 58% iORR, including in patients with symptomatic metastases to the brain. However, the duration of responses achieved on targeted therapy (TT) is shorter than for extracranial disease prevalence. On the other hand, regardless of the presence of a BRAF mutation, immunotherapy (PD-1 monotherapy) achieves a response in approximately 20-22% of patients, but these responses are more durable, although fewer than on TT. The combination of CTLA-4 + PD-1 checkpoint inhibitors produces long-lasting responses with a iORR of 51-54%. However, the achievement of these results and an overall increase in life expectancy with immunotherapy is mostly possible in symptom-free patients and in patients receiving low or no doses of glucocorticosteroids (10 mg or less on prednisolone). Therefore, for symptomatic patients, especially those whose tumors have been identified with a BRAF mutation, a combination of targeted therapy, which would quickly achieve an objective response in 58%, and anti-PD1/PDL1 immunotherapy, which is likely to increase the duration of the response achieved and give a chance for a sustained remission, looks promising. This article provides an overview of key studies and our own experience with the triple combination in metastatic brain lesions.

Introduction. Olaparib is the only PARP inhibitor approved in Russia for the maintenance therapy for BRCA-positive ovarian cancer after frontline chemotherapy. We conducted a real-world analysis of olaparib efficacy and safety for this indication.

Aim. To assess the efficacy of PARP inhibitors in real-world clinical practice.

Materials and methods. Patients with stage III-IV BRCA-mutated ovarian cancer who received olaparib maintenance therapy in expanded access program in 03.2019-12.2020 timeframe. Briefly, key inclusion criteria were: serous or endometrioid highgrade ovarian cancer; pathogenic BRCA1/2 mutation; primary or interval debulking; complete or partial response to frontline platinum-based therapy. Olaparib was administered as tablets (300 mg BID) up to 2-years, disease progression or unacceptable toxicity, whichever occurred first. The primary endpoint of the study was progression-free survival (PFS), overall survival (OS) and safety were key secondary endpoints. Statistical analysis was done with R and RStudio software.

Results and discussion. 23 patients were enrolled. Median age was 49 years, all patients had high-grade serous adenocarcinoma histology. Complete debulking at primary or interval surgery was achieved in 30% of patients. With median follow-up time equal to 22 months, median PFS and OS were not reached. The 2-year PFS and OS were 65 and 84%, respectively. Grade 3-4 adverse events was detected in 7 (30.4%) patients.

Conclusion. Our results supports high efficacy of olaparib in real clinical practice setting reported in the SOLO1 trial.

Metastatic renal cell carcinoma accounts for almost 85% of all cases of malignant neoplasms of the kidney. Sunitinib is an anti-angiogenic tyrosine kinase inhibitor, one of the indications is the treatment of mRCC in adults. Sunitinib is an oral tyrosine kinase inhibitor that includes the vascular endothelial growth factor receptor (VEGFR) and the platelet-derived growth factor receptor (PDGFR). Sunitinib is primarily used as a first-line drug at an initial dose of 50 mg. 1 time per day for 4 weeks followed by a 2-week break. Recommendations, if dose modification is necessary, indicate a dose reduction to 37.5 mg per day and, if necessary, a further dose reduction to 25 mg per day. Another promising regimen is to continue the daily dose of 50 mg with more frequent breaks: 2 weeks of treatment followed by a pause of 1 week. The analysis presented in the article shows that patients with mRCC who switched to sunitinib 2/1 regimen due to adverse events from the standard 4/2 regimen do show an improved safety profile. There is evidence of a significant reduction in overall grade 3-4 toxicity, as well as a reduction in the incidence of specific drug toxicity such as fatigue, hypertension, hand and foot syndrome, and thrombocytopenia. The article presents a clinical observation of a patient with advanced renal cell carcinoma who has a contraindication for immunotherapy. The patient underwent cytoreductive laparoscopic resection of the left kidney. Taking into account the existing contraindications to immunotherapy, the patient was prescribed sunitinib monotherapy at the standard dosage in the first line. After two courses of therapy, due to adverse events, the therapy regimen was changed from 4/2 to 2/1. The ongoing therapy in the 2/1 regimen demonstrated a satisfactory safety profile with adequate clinical efficacy.

Urothelial cancer occupies a significant place in the routine practice of cancer treatment. Systemic antitumor treatment of patients with metastatic urothelial cancer in the first line is currently well studied, has its own standards, implemented in clinical practice. However, the problem of choosing antitumor treatment for patients with metastatic urothelial cancer in the second line remains relevant. Vinflunine is one of the treatment options for such patients. This article presents the case of successful treatment of metastatic urothelial cancer in the second line with vinflunine. A 63-year-old patient with a diagnosis of C65 Urothelial cancer of the pelvis of the left kidney T3N0M1, stage IV, bone metastases. Condition after cytoreductive left-sided nephrectomy, para-aortic lymphadenectomy from 04/16/2021. Concomitant pathology: Anemia. Diabetes mellitus type 2 Hypertonic disease. As the 1st line of treatment, 6 courses of CT were performed according to the scheme: Cisplatin + Gemcitabine. The effect was evaluated according to MSCT data of 3 zones and bone scintigraphy in accordance with Recist 1.1. The best response was obtained after the 4th cycle in August 2021 in the form of stabilization. October 2021 follow-up examination revealed progression. Since October 2021, chemotherapy of the 2nd line with Vinflunin is carried out in mono mode. All AEs are well controlled and do not require discontinuation of the drug. According to the results of the control examination, stabilization was achieved. Thereby vinflunine has been shown to be effective as a second-line treatment for platinum-resistant recurrent urothelial cancer.

Introduction. Diffuse large B-cell lymphoma (DLBCL) is the most common (30-35%) type of B-cell lymphomas. Only about 60% of all newly diagnosed advanced-stage DLBCL can be completely treated by x6 CHOP-R only. High dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation in the first remission (upfront auto-HSCT) can serve an option to improve prognosis in these patients (pts).

Aim. To improve prognosis in DLBCL IV stage, IPI ≥2 pts by upfront auto-HSCT.

Materials and methods. Included 105 pts: DLBCL NOS, age 18-65, stage IV, IPI ≥2, CR/PR after x6 CHOP/EPOCH + R from 2010 to 2019 at NMRC of Oncology named after N.N. Petrov of MoH of Russia were retrospectively analyzed. HSCT group includes pts with upfront HDCT followed by auto-HSCT (n = 35). The control group includes pts with non-invasive follow-up after induction only (n = 70). Primary endpoints were overall (OS) and progression-free survival (PFS). Secondary endpoints were response rate, relapse rate and treatment toxicity.

Results and discussion. The 3-yr OS (p = 0.01) and 3-yr PFS (p = 0.018) were significantly higher in HSCT group. The complete response rate was significantly increased after upfront auto-HSCT (p < 0.001). Early relapse served as an independent negative prognostic factor in OS (p < 0.001) and experienced statistically less in HDCT group (p = 0.027). Early (ER) and late relapse (LR) rate were higher in pts with DEL (ER - p < 0.001, LR - p < 0.001 in control group and ER - p < 0.001, LR -p = 0.013 in all pts). The overall relapse rate was higher if pts had >1 extranodal site with lung involvement (p < 0.004 in the control group and p = 0.021 in all pts). Prognostic models suggested DEL and presence of >1 extranodal site with lung involvement as an independent negative prognostic factors for increasing the relapse probability in two years after treatment.

Conclusion. Upfront HSCT can serve as a clinical option to consolidate the first remission in IV stage DLBCL pts with DEL and/or >1 extranodal sites with lung involvement.

Introduction. Erythropoietin (EPO) application is a pathogenetic method for anemia correction in cancer patients.

The purpose of study. Clinical evaluation of the efficacy and safety of Eralfon® (epoetin alpha) in treatment for anemia in patients with malignant solid tumors during medical anticancer therapy.

Materials and methods. We analyzed the data on anemia treatment with Eralfon® in 184 patients with malignant solid tumors receiving various medical anticancer therapies. Eralfon® was injected subcutaneously 12 000 IU 3 times per week or 40 000 IU once a week. Clinical antianemic effect, the time to maximum antianemic effect, adverse events (AE) were analyzed.

Results. Patients were stratified by the grade of anemia, stages of treatment, presence of bone metastases, bleeding, previous medical and radiation anticancer therapies, dosage of Eralfon®. The time to effect was shorter in patients under 65. There were no significant differences in efficacy depending on the dosing regimen of Eralfon®. Efficacy was lower in patients with advanced tumors, especially in bone metastases. A history of tumor bleeding, chemotherapy and/or radiation therapy prolonged the period of hemoglobin recovery to normal values. Arterial hypertension and venous thrombosis were the most common AE associated with Eralfon®. Eralfon® 12 000 IU 3 times per week caused less frequent complications, with no cases of ossealgia and myalgia.

Conclusion. Eralfon® demonstrated clinical efficacy in treatment for anemia in patients with solid malignant tumors receiving medical anticancer therapy. Dosage of 12 000 IU 3 times per week provided better control of the antianemic effect and adverse events.

The EGFR mutation is one of the most common mutations in malignant neoplasms. The epidermal growth factor receptor (EGFR) is a growth factor receptor that induces cell differentiation and proliferation when activated by binding one of its ligands. The receptor is located on the cell surface, where ligand binding activates a tyrosine kinase in the intracellular region of the receptor. The tyrosine kinase phosphorylates a number of intracellular substrates and further activates pathways leading to cell growth, DNA synthesis and oncogene expression. Gene amplification is a process characterized by an increase in the copy number of a restricted region in the chromosome shoulder, which is associated with overexpression of the corresponding amplified gene. Amplification of the EGFR gene is detected in about 40% of glioblastoma cases. It should be noted that EGFR gene amplification is accompanied by the acquisition of many mutations, which include intragenic deletions and point mutations. The most common EGFR mutation in glioblastomas of the brain is a deletion in exon 2-7 (EGFRvIII) frame, which occurs in 50% of all cases of EGFR-amplified glioblastoma. Despite great advances in molecular biology and targeted therapies, patients with non-small cell lung cancer (NSCLC) and glioblastoma still lead in mortality. Most of them have “classical” EGFR mutations (deletions in exon 19 and 21), but 15-20% of patients have rare mutations, which most often include point mutations, deletions and insertions in exon 18 and 25. Thus, rare EGFR mutations are a promising diagnostic and therapeutic target in cancer. This review summarizes data on the role of EGFR in the carcinogenesis of NMPL and glioblastoma. The literature search was performed using the Pubmed database.

Introduction. Patients with hormone-receptor-positive (HR+) breast cancer (BC) over 40 years old who take tamoxifen are not subject to mandatory castration. However this cohort of patients is not homogeneous.

Aim. The present study is aimed at studying the features of ovarian steroidogenesis in perimenopausal breast cancer patients receiving adjuvant hormone therapy (HT) with tamoxifen.

Materialy and methods. The study included 82 patients aged 42 to 53 years with GH+BC who received HT with tamoxifen 20 mg daily. Within 9 months from the start of HT in patients, the levels of estradiol and follicle-stimulating hormone in the peripheral blood were studied every 3 months.

Results. In 66.7% of patients who received chemotherapy (CT), the development of amenorrhea was noted. Half of the patients in the HT-only group demonstrated amenorrhea. Oligomenorrhea was observed in 20.8% and 16.7% in each group, respectively. The incidence of amenorrhea in women treated with chemotherapy was higher (OR 2.02; 95% CI: 0.73-5.67), but the differences were not statistically significant (p = 0.1766). In the general cohort, in 15.7-16.8% of patients, the level of estradiol exceeded 251 pg / ml - the upper limit of the norm of the follicular phase of the menstrual cycle. Differences between groups in the incidence of estradiol levels > 251 pg/ml were statistically significant (p = 0.0293). 3.4-5.6% of patients in the total cohort (depending on the period of observation) had an estradiol level > 649 pg / ml, which corresponded to the highest ovulatory value.

Conclusions. Against the background of HT with tamoxifen in some perimenopausal patients hyperestrogenism is observed which indicates the implementation of the effect of induction of ovarian steroidogenesis and can be considered as an additional potential risk factor for the progression of HR+BC. Amenorrhea after CT is not a reliable marker of ovarian suppression.

Introduction. The emergence of new markers that determine the choice of therapy for metastatic colorectal cancer (CRC) has led to an increase in overall survival. The optimal treatment tactics now take into account both clinical and molecular-genetic characteristics of the tumor.

Aim. Investigation of the features of the KRAS, NRAS and BRAF mutations and amplification of the HER2 gene depending on microsatellite instability (MSI) in CRC.

Materials and methods. The study included 400 patients with CRC. MSI, BRAF V600E mutation, mutations in the KRAS and NRAS genes was identified to them. MSI was determined by fragment analysis, and mutations in the KRAS, NRAS, BRAF genes by realtime PCR. HER2 amplification was determined in 100 patients with a negative RAS/BRAF. NTRK translocations were determined in all patients with MSI. Data on preoperative levels of CEA and CA19-9 were obtained from 185 patients.

Results and discussion. The prevalence of MSI was 6.8%. The prevalence of KRAS, NRAS, BRAF mutations in CRC with MSI was 66.7%, and in CRC with MSS - 52.3%. In patients with MSI, the level of CEA was lower than in MSS (p = 0.0061). The overall prevalence of KRAS and NRAS mutations was 45% and 2.5%. The overall prevalence of the BRAF V600E mutation was 5.8% and was more common in MSI-positive tumors (p < 0.0001). Regardless of MSI, BRAF-positive tumors were characterized by right-sided localization (p < 0.0001), category T3-4 (p = 0.013), lymph node involvement (p = 0.004), carcinomatosis (p = 0.046), high levels of CA19-9 (p = 0.014). HER2 amplification was found in 7% of wild-type RAS/BRAF cases and was associated with rectal cancer (p = 0.044), category T3-4 (p = 0.041), and distant metastases (p = 0.038). HER2 amplifications and NTRK translocations were not detected in cases with MSI.

Conclusion. MSI-positive CRC had a higher prevalence of mutations in major genes. CRC with the BRAF V600E mutation and HER2 amplification had aggressive clinical and morphological parameters.

Introduction. Radiation therapy is an effective method of treating pain in patients with bone metastases, but during radiotherapy there is often an increase in pain. The presence of a new drug containing a combination of orphenadrine and diclofenac in oncologists expands the possibilities of analgesia.

Aim. To evaluate the efficacy and safety of the use of a fixed combination of diclofenac and orphenadrine in patients with pain due to metastatic bone damage during radiotherapy.

Materials and methods. The patients were randomized into two groups: the first group (n = 30) received the drug Neodolpasse intravenously once a day for two days; the second - 2 times a day (n = 30) - 2 days. Efficacy was evaluated based on the following measurements: intensity of pain by NRS immediately after administration of the drug, after 30 minutes, after 1, 2, 4 and 24 hours, the dynamics of daily doses of analgesics.

Results and discussion. In group 1, a meaningful decrease in pain intensity (p < 0.05) from 48.7 ± 10.6 mm to 26.8 ± 10.7 mm was achieved 30 minutes after the completion of infusion. The pain intensity measured by the Numeric Rating Scale (NRS) reached its minimum value 2 hours after the completion of infusion (22.5 ± 12.0 mm). In group 2, the pain intensity decreased 30 minutes after the completion of infusion, a meaningful decrease (p < 0.05) in pain intensity was achieved from 56.5 ± 9.8 mm to 34.0 ± 10.5 mm, and up to 29.8 ± 10.2 mm after the second dose. The pain intensity decreased by 45.9% in group 1 and by 47.9% in group 2 towards the end of the Neodolpasse therapy cycle. During the study, two mild to moderate adverse events (nausea, drop in blood pressure) that did not require any significant drug therapy were observed.

Conclusion. The results of the study confirm that the use of the drug according to the proposed method is a safe and effective way of treating pain syndrome during radiotherapy in patients with metastatic bone damage.

HCC is considered refractory when it comes to progression during treatment with TKIs (sorafenib, lenvatinib). The combined immunotherapy of nivolumab with ipilimumab was studied in the one cohort of CheckMate-040 study, excluding immunotherapy-naive patients. The question of choosing an immunotherapy option in the presence of several options remains open. Like separate issue remains the prospect of using immunotherapeutic combinations after progression on immunotherapy. We present a long history of treatment of a patient with advanced HCC, which has been observed for 8 years at the Blokhin National Medical Research Center of Oncology. The example of this clinical observation shows the result of a multidisciplinary individual approach to the treatment of advanced HCC with the background of hepatitis C virus without liver cirrhosis (Child -Pugh A), stage BCLC-C. During this period of time, the patient received 5 lines of antitumor therapy, which were repeatedly supplemented with TACE procedures, radiation therapy and surgical treatment, with oligometastatic progression. The longest period of therapy without progression was recorded with the use of Nivolumab 240 mg in the 3rd line for 18 months, without clinically significant toxicity. The disease progressed with damage of the brain substance, one-stage microsurgical removal of metastases was performed, followed by EBRT. 4-line TKI therapy was not long-term. Due to the lack of a potential therapy option, it was recommended to resume therapy with anti-PD-1 with the addition of anti-CTLA-4, which gave its objective effect. Since November 2021 patient received 4 courses of Nivolumab 1 mg/kg + ipilimumab 3 mg/kg once every 3 weeks, and a partial effect was achieved (-42% according to RECIST 1.1). Then we performed nivolumab 240 mg IV every 2 weeks — which the patient continues to the present time.

Brain metastases (BM) are associated with poor prognosis, short overall survival, and severely compromised quality of life in patients with advanced breast cancer (BC). BM create therapeutic challenges in BC due to the difficulty for the majority of drugs to cross the blood-brain barrier. Hormone-positive HER2-negative breast cancer usually progresses slowly compared to other subtypes and it is the most common subtype among patients with BC. The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have rapidly transformed breast cancer treatment landscape within past few years. Integrating CDK4/6 inhibitors in clinical practice significantly improved both progression-free and overall survival in all patient population, including patients with BM. In this article we summarize the results of phase III randomized controlled trials (MONALEESA-2, MONALEESA-3, MONALEESA-7, and Completion-1), suggesting the efficacy of the combination of ribociclib with various endocrine therapies, and present a clinical case discussion of a patient with advanced hormone-positive HER2-negative BC with brain, hepatic and bone metastases treated with combined targeted and endocrine therapy.

Non-small cell lung cancer is a very heterogeneous group of diseases. When choosing an effective patient management strategy, an oncologist focuses on the stage of the disease, the morphological form of the tumor, as well as its molecular genetic markers. Most of the targeted mutations in lung cancer today are in adenocarcinoma. The standard for detecting this type of cancer in 2022 is the determination of mutations in the EGFR genes (18-21 exons) and BRAF (V600E), translocations of the ALK and ROS1 genes, and determination of PD-L1 status regardless of gender, age, and history of smoking. Often, lung cancer is detected in the advanced stages, but the detection of ALK gene translocation can give the patient a high chance of a longer life expectancy and long-term control of the disease. In this article, on the example of a clinical case of a patient with ALK-positive lung adenocarcinoma, a multidisciplinary approach to the management of cancer patients, long-term control of the disease with the use of the second-generation targeted medication alectinib, as well as treatment options for disease progression are demonstrated.

Hereditary breast cancer (BC) accounts for about 5-10% of cases. BRCA-associated tumors have been identified as a separate group of malignant neoplasms with distinctive clinical manifestations and specific treatment features. Understanding of biological mechanisms leading to cancer in BRCA1/2 mutation carriers and discovery of potential molecular targets, such as poly (ADP-ribose) polymerase (PARP), involved in base excision repair mechanisms, led to the development of a new class of targeted drugs belonging to the PARP inhibitors group. PARP inhibition leads to the preservation of single-stranded DNA breaks, the arrest of the replication fork, and the realization of the “synthetic lethality” phenomenon due to the inability to repair double-stranded DNA breaks by homologous recombination in cells with mutations in the BRCA1/2 genes. Two randomized trials OlympiAD and EMBRACA evaluated and proved the effectiveness of PARP inhibitors in patients with metastatic BRCA-mutated HER2-negative breast cancer in comparison with standard chemotherapy. At the same time, data on the potential use of PARP inhibitors for the treatment of BRCA-mutated HER2-positive breast cancer patients are extremely limited. This article presents a clinical example of the use of olaparib in a patient with BRCA-mutated HER2-positive metastatic breast cancer.

The development of a new area of antitumor drug therapy, immunotherapy using immune checkpoint inhibitors targeting PD-1/PD-L1, has significantly changed approaches to the treatment of advanced non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated the clinical benefit as well as the long-term effect of these drugs. Currently, the problem of treatment of patients after disease progression against the background of the use of checkpoint inhibitors is relevant. Equally relevant is the issue of choosing the correct and most effective treatment tactics for NSCLC patients with oligoprogression, as well as with abscopal effect. This paper describes a clinical case of a patient with lung adenocarcinoma without driver mutations with PD-L1-positive status, who was treated with nivolumab after second-line chemotherapy for disease progression, and after oligoprogression of the disease into the brain was given stereotactic radiotherapy of metastatic lesion and continued therapy with nivolumab. Partial regression of metastases was achieved with a prolonged effect on the background of continued treatment with nivolumab for 24 months. Tolerability of therapy was satisfactory: no adverse events were observed. The patient retained the result for 1.5 years.

Radiation therapy (RT) is one of the main methods of treatment of malignant tumors. More than 70% of patients with malignant tumors of various localizations require RT as part of their combination treatment. Cutaneous reactions can occur in up to 95% of patients during or after their treatment. Clinically, cutaneous radiation reactions are manifested by hyperemia, edema, burning and itching of the skin, which cause significant discomfort to patients and reduce their quality of life, especially if these processes are localized on the exposed parts of the body. Also in some localizations of malignant tumors together with RT are used antitumor drugs, which, in turn, increases the frequency of skin toxicity and worsens the clinical picture. Timely detection of the above symptoms, their adequate comprehensive therapy with the use of basic skin care products can significantly reduce or eliminate their manifestations. This article presents the clinical experience of using La Roche-Posay products during radiotherapy and chemoradiotherapy (the patients gave their informed consent for the publication of the clinical observations).

Metastatic triple-negative breast cancer remains the most unfavourable among all breast cancer subtypes from the prognostic point of view. Despite the active introduction into practice of combinations of cytostatics with immunotherapeutic agents, as well as PARP inhibitors, sequential lines of chemotherapy with the median overall survival which does not exceed 15 months remains the main method of treating patients in this group. This breast cancer subtype is characterized by a rapid development of drug resistance at the early stages of systemic treatment and a predominantly visceral progression, which determines a low life expectancy in patients. The combination of capecitabine and ixabepilone has proved to be effective in the treatment of tumours that are resistant to taxanes and anthracyclines. The use of this combination is characterized by an acceptable and controlled toxicity profile. This article presents a clinical case of therapy with a combination of ixabepilone and capecitabine of a patient with breast cancer progression during the previous therapy of taxanes, a platinum-based doublet chemotherapy and eribulin. This approach, together with symptomatic laparocentesis and pleurodesis, allowed for overall survival exceeding 45 months with the preservation of a satisfactory functional status of the patient.