Introduction. Lung cancer remains the one of the most common and fatal cancers in the world. For a long time, chemotherapy was the only treatment option for metastatic lung cancer. Currently, immunotherapy became the one of the preferred options of treatment.

The purpose of our work was to evaluate the long-term results of using the PD-1 inhibitor nivolumab in real-world settings.

Materials and methods. 108 pretreated patients with metastatic NSCLC were included in this non-randomized, observational study. The median follow-up time was 54.5 months.

Results. Median overall survival was 8.8 months (6-12, 95% CI). The five-year overall survival rate was 19.4%. Median progressionfree survival was 3.9 months (3-5, 95% CI). The five-year progression-free survival rate was 7.7%. Overall response rate (ORR) was 18%. In patients with ORR, the median overall survival was not achieved. Prolongation of immunotherapy after disease progression had a positive effect on the overall survival of patients. Clinically significant immuno-related adverse events developed in 21% of patients, but only 7.3% showed the development of adverse events grade 3-4 that required discontinuation of immunotherapy. A rare complication that we met was a case of encephalopathy, to which the patient achieved durable complete response despite discontinuation of immonotherapy.

Conclusion. Received survival, efficacy and safety data may inform treatment decisions for patients with metastatic NSCLC in real world settings.

In the recent years the growing life expectancy of the population and increasing cancer burden in elderly patients substantiate the urgent need for the search of optimal cancer treatment strategies. This article provides an overview of the current literature on the efficacy and safety of checkpoint inhibitors in the elderly population. A literature search for published studies using Medline (PubMed) and Elibrary databases was performed. All studies containing data on treatment results including tumor response criteria, treatment response rate, tumor control rate, overall survival were included. Case studies, animal studies and studies containing duplicate results were excluded from the analysis. In elderly patients with cancer there is a substantial number of comorbid conditions and functional disorders, which may decrease the efficacy and modulate the tolerability of immune checkpoint inhibitors (ICI). Besides, different changes associated with immunologic ageing, including thymolysis, increase of the number of memory B-cells and a decrease of hematopoesis intensity are observed. Several studies performed a comparative analysis of efficacy and toxicity of ICIs in elderly and younger patients. In most cases similar results for efficacy and toxicity were demonstrated. To evaluate the toxicity and the influence of treatment on functional status and other important measures in geriatric population further studies of factors, influencing the tolerability and treatment response of newer ICI in elderly cancer patients are needed, including additional adverse events associated with treatment.

Breast cancer (BC) is the most common cancer and the primary cause of cancer death. About 5 to 10% of breast cancer cases have a hereditary background. BRCA-related breast cancer is characterized by more aggressive phenotype than sporadic breast cancer. Olaparib is one of the drugs that can improve the results of treatment in this group of patients. Several phase I and II trials have shown that PARP inhibitors are effective as monotherapy in patients with metastatic breast cancer and germline BRCA1/2 mutation. A randomized, open-label, phase III trial (the OlympiAD study) comparing olaparib monotherapy and standard treatment in patients with HER2-negative mBC and a germline BRCA1/2 mutation showed hopeful results. The olaparib group registered an objective response of 59.9% compared to 28.8% in the standard therapy. A complete response was reported for 9.0% of patients in the olaparib group and 1.5% in the standard therapy group. A clinical case of treatment of a triple-negative breast cancer patient with BRCA1 c.5382insC (rs80357906) mutation is presented. There was a response to over 9-month olaparib therapy after progression on two systemic chemotherapy lines. The pedigree of the patient was also considered, her relatives with malignant tumours were identified. Screening tests were done to detect the patient’s relatives with a germline mutation in the BRCA1 gene. More thorough tests are planned to be done for early detection of malignant neoplasms in the identified healthy relatives with BRCA1 c.5382insC mutation.

Tyrosine kinase inhibitors of the first, second and third generations are the main treatment method for non-small cell lung cancer with EGFR mutation. About 60% of patients progressing on a first-generation or second-generation tyrosine kinase inhibitor acquire T790M mutation. An alternative is first-line osimertinib, but second-line treatment options are limited, and therefore it is important to find a strategy that allows to extend the effective treatment of TKI. One of the rational approaches is the use of a combination of a first-generation tyrosine kinase inhibitor with anti-VEGF agents. The available information sources show an increase in the effectiveness of the combined use of erlotinib and antiangiogenic drugs-bevacizumab and ramucirumab. The combination of erlotinib and bevacizumab in several studies of the second — third phase, led to a statistically significant increase in progression-free survival, but did not show a significant increase in overall survival. In the Phase 3 RELAY study, the combination of erlotinib and ramucirumab showed comparable efficacy with the third-generation TKI — osimertinib in the first line, however, overall survival results are not yet available. At the same time, there are more opportunities to choose the secondline mode, taking into account the known frequency of detection of the T790M mutation. The optimal treatment sequence is discussed, with the option of prescribing a combination of erlotinib with bevacizumab or ramucirumab in the first line and osimertinib in the second in the presence of the T790M mutation. In such patients, osimertinib may be prescribed in the second line.

With an increasing number of alternative effective therapies available for patients, there is an increasing need for a more accurate selection for therapy (compared to observation, for example, after radical surgical treatment), selection of the optimal therapy (prediction of primary resistance or, conversely, high sensitivity), and criteria for stopping treatment (complete tumor elimination) or changing therapy (molecular, i.e. preclinical and preradiological progression). We look for answers to all these questions in a variety of biomarkers. Many clinical markers (e.g. ECOG performance status or disease prevalence), molecular genetic (e.g. such as mutations in the BRAF gene, NRAS, NF1, TMB), immunological (e.g. tumor infiltration by lymphocytes and expression of PDl1, PDl2, PD1 or other «immune checkpoints» on tumor cells and microenvironmental cells), as well as factors circulating in the blood and plasma (e.g., blood cell-to-cell ratio, circulating tumor DNA or cytokines in the peripheral blood). In this study, we have tried to analyze the data accumulated so far and attempt to relate them both to current clinical practice and available therapies, as well as to outline the prospects for upcoming research in this area. In our opinion, the available data may influence the current routine practice of oncologists and allow for a more careful choice of first-line therapy to maximize benefit and minimize harm. Although it is likely that some organizational effort will be needed to change established clinical practice in order to identify such biomarkers.

The development of a new direction in anticancer medical therapy – the use of immune checkpoint inhibitors targeting PD-1/ PD-L1 and CTLA-4 – has significantly changed the approach to tumor treatment in the last few years. The PD1 blocker nivolumab in major registered clinical trials improved overall survival, including in metastatic melanoma, with a favorable toxicity profile. However, its efficacy in patients with brain metastases from melanoma was poorly studied, since the inclusion criteria  for  most clinical trials do not envisage recruiting such patients. The  immune-mediated toxicity of  immune checkpoint inhibitors is currently well enough studied. However, cases of cutaneous toxicity are quite rare and present certain difficulties for differential diagnosis and treatment. This article presents two cases of effective nivolumab treatment in patients with generalized BRAFwt and BRAFmut cutaneous melanoma. The  first case is of  interest due to the  presence of  brain  metastases in the patient. Nivolumab therapy helped achieving complete regression of intracranial metastases with the long-term effect. The second case, in addition to effective treatment, demonstrates a rare manifestation of skin toxicity – vitiligo on the face and upper extremities.

In 2019 malignant neoplasms of the female reproductive system (ovarian cancer, (OC), endometrial carcinoma (EC) and cervical cancer (CC) were diagnosed in 58 860 patients – 17.6% of all malignant tumors in women in Russia. The morbidity and mortality rates from these neoplasms remain high over the past 10 years. This article provides a detailed review of the current evidence base for  the  use of  various immunotherapeutic agents in  mentioned malignant neoplasms. It has been demonstrated that in  relapsed OC (ROC), the  only proved indication for  immunotherapy is tumors with microsatellite instability (MSI), whereas PD-L1 does not have an independent role in this disease. MSI occurs in approximately 8% of patients with metastatic OC. A significantly higher frequency MSI — up to 25% is detected in metastatic EC. MSI-positive subtype of the disease is characterized by an extremely high sensitivity to immunotherapy - the  rate of  objective response with pembrolizumab exceeds 50%. For  MS-stable  EC, the  combination of  pembrolizumab and lenvatinib is an effective therapeutic option. In  advanced CC, on the other hand, PD-L1 has a predictive role for immunotherapy efficacy — the KEYNOTE-158 study showed that about 15% of  patients with extensively pretreated metastatic PD-L1-positive CC can achieve long-term remission with pembrolizumab compared to 0% in PD-L1 negative tumors. Current evidence shows that PD-L1 expression can be observed in ≥ 30% of patients.

Renal cancer is a common malignancy. The frequency of renal cell carcinoma (RCC) in the structure of oncological diseases is steadily increasing. Despite the migration of the stage towards an increase in the frequency of primary detection of localized forms of the disease, renal cancer belongs to the aggressive and unpredictable malignant neoplasms. One third of patients already have distant metastases at the time of diagnosis. Surgery is the only radical method of treatment of renal cancer. However, despite the successes of surgery in the treatment of RCC, according to various data, more than 30% of radically operated patients show dissemination of the tumor process during follow-up. Radiation therapy and chemotherapy are ineffective in treating metastatic RCC (mRCC). The results of nonspecific immunotherapy in the treatment of metastatic renal cancer were also unsatisfactory. Progress in the study of molecular biology has led to the discovery of a new group of anti-tumor drugs related to angiogenesis inhibitors. The use of targeted therapies has increased the efficacy of drug therapy in the treatment of mRCC several times over the use of cytokine immunotherapy. One of the first such drugs registered in 2007 for the treatment of mRCC was sunitinib, which in a number of clinical trials has demonstrated the greatest efficacy and acceptable toxicity. Along with new drug regimens, the multikinase inhibitor sunitinib remains the drug of choice for first-line therapy of inoperable locally advanced and disseminated clear cell and non-small cell RCC in patients with favorable prognosis. The literature review presents a critical analysis of the data related to sunitinib research in kidney cancer and changes in the position of monotherapy with this drug in advanced forms of the disease.

Gastric cancer (GC) is one of the most common malignant tumours both in Russia and in the world. The drug therapy with consistent use of several therapy lines is the main method for treatment. The number of chemotherapy drugs, which are effective for the treatment of this type of malignant tumours, is limited; the range of targeted drugs is also narrow and includes trastuzumab in the first-line regimen for the treatment of HER2-positive gastric cancer and ramucirumab in the second-line regimen. Immune checkpoint inhibitors made a revolution in the treatment of many cancers. The efficacy of nivolumab, T cell inhibitory receptor of PD-L1, has been proven in the third-line regimen in disseminated gastric cancer. The ATTRACTION-2 randomized study showed that nivolumab significantly increased the median overall survival (from 4.14 to 5.26 months, p < 0.0001), progression-free survival (from 1.45 to 1.61 months, p < 0.0001); objective response with a median duration of 9.5 months was achieved in 11.2% of patients, stable disease in 29.1%. The median time to progression was 1.61 months. The toxicity of the treatment was quite low and led to discontinuation of treatment in only 1% (n = 4) of patients, who had previously received massive chemotherapy. Only patients from Asia took part in the ATTRACTION-2 study. However, its results were confirmed in the CheckMate-032 study in the non-Asian patient population: the objective response rate was 12%, the median DOR was 7.1 months, the median progressionfree survival was 1.4 months, and the median overall survival was 6.1 months. Nivolumab was effective for the treatment of MSI-H and MSS, PD-L1-positive and PD-L1-negative tumours. Nivolumab is a recognized and well-tolerated standard of late-line therapy in disseminated gastric cancer. The range of indications for its prescription will be expanded in the nearest future.

The COVID-19 pandemic has affected all medical fields and brought up a lot of serious problems. The features of the COVID-19 infection in patients with cancer are important to understand. According to many articles, patients with cancer are more vulnerable to COVID-19 infection. Patients undergoing anticancer treatment have 1-4% morbidity rate. Patients with hematological diseases and lung cancer are at higher risk of SARS-CoV-2 infection and also have more severe symptoms and complications. In this article we discuss the effect of the tumors on the immune system and comprehend the pathogenesis of the coronavirus disease according to its impact on the immunity. Moreover, in the review we analyze available data about the influence of the different types of cancer therapy (chemotherapy, target therapy, radiotherapy and immunotherapy) on the severity of the COVID-19 infection. Evidence on the effect of chemotherapy on severity and mortality from COVID-19 is contradictory. Whereas there are some authors concluding that chemotherapy treatment is not affecting the severity of COVID-19 disease, there are also some works where the connection between these facts was established. At the same time target therapy, radio- and immunotherapy most likely do not worsen the SARS-CoV-2 infection and are not associated with the development of complications. But it’s important to say that the amount of data available for today is insufficient to make a unambiguous conclusion.

The frequency of drug-induced pancreatitis (LIP) is from 2 to 5% of all cases of acute pancreatitis (OP), but it is much more common in risk groups – among children and HIV-infected patients. The use of a number of drugs (drugs) is associated with the development of lipids, among them a special place is occupied by antitumor drugs due to the great medical and social significance of oncological diseases and the appearance in recent years of a large number of new antitumor drugs. The purpose of this review was to review the literature data on antitumor drugs, the use of which is associated with the development of lipids. LI OP developed in 1.8% of patients treated with nivolumab or pembroluzumab. In total, in 14 phase 1-3 studies on the efficacy and safety of ipilimumab, the development of OP was reported in less than 1% of the subjects. Therapy with molecular-targeted targeted drugs, such as tyrosine kinase inhibitors (TKI) or other representatives of the kinase inhibitor class, is also associated with the development of OP. The HP database of the World Health Organization (WHO, World Health Organization Adverse Drug Reaction database) contains reports of individual clinical cases of OP development during treatment with proteosome inhibitors and antibody-drug conjugates. It is known that the following antitumor drugs are also associated with the development of pancreatitis: 6-mercaptopurine, L-asparaginase, tamoxifen, cisplatin, cytarabine, ifosfamide, paclitaxel, docetaxel, oxaliplatin, capecitabine, periwinkle alkaloids, cytosine, cisplatin, interferon alpha-2b, doxorubicin, tamoxifen, gefitinib, vinorelbine, levamizole, methotrexate, 5-fluorouracil, capecitabine, trans-retinoic acid.

Introduction. The gold standard for the treatment of patients with a localized form of pancreatic cancer is radical surgical intervention. It is characterized by a high frequency of postoperative complications and is not performed in patients with a weakened general functional status and the presence of multiple severe concomitant somatic pathology.

Purpose. The aim of this study is a assessment of the safety and effectiveness of combined treatment with the inclusion of gemcitabine chemotherapy and HIFU therapy in somatically inoperable patients with localized pancreatic adenocarcinoma of the elderly and senile age.

Materials and methods. This study involved 15 patients with stage II (T3N0-1M0) disease aged 60 years and older, with a performance status ECOG 2 and a high operational and anesthetic risk, who received palliative combined treatment on the basis of the P. Hertsen Moscow Oncology Research Institute in the period from 2017 to 2020. HIFU therapy was performed on the HIFU2001 (Shenzhen Huikang Medical Apparatus Co., Ltd.), local treatment sessions were carried out in the amount of 3–8 per course, conducted daily, in the intervals between days of intravenous administration of gemcitabine at a dosage of 1000 mg/m2 (1, 8, 15 days every 4 weeks).

Results. Adverse events of systemic drug therapy were observed in 9 (60%) patients, local complications of HIFU therapy — in 6 (37.5%) patients. 6 months after the start of treatment, pain control was achieved in 87.5% of patients, local progression of the disease was detected in 2 (13.3%) cases, and a partial tumor response was determined in 2 patients and stable disease in 11 patients. The median overall survival was 19 months, and the median progression-free survival was 12 months. The overall 1-, 2-, and 3-year survival rate was 80%, 20%, and 13%, respectively, and the 1-year progression-free survival rate was 54%.

Conclusions. The results of this study demonstrate the prospects of using a combination of HIFU therapy and gemcitabine monotherapy in somatically inoperable patients with localized pancreatic adenocarcinoma of the elderly and senile age.

According to the data of the world statistics, gastric cancer (GC) occupies the 5th place by morbidity and the 3rd one by mortality among malignant neoplasms. A significant proportion of patients are elderly patients, the proportion of which in real clinical practice can reach up to 60%. Ramucirumab is among the standards of second-line drug therapy both in monotherapy and in combination with paclitaxel. The feasibility of prescribing ramucirumab to patients with disseminated cancer of the elderly and its satisfactory tolerability is shown in a subgroup analysis of the REGARD and RAINBOW studies. The use of paclitaxel, included in the standard first-line regimens, may be limited by persistent neurotoxicity, a side effect of platinum derivatives. In this regard, the effectiveness of the combination of ramucirumab with the FOLFIRI regimen as a second-line therapy began to be studied. The article presents a clinical case of achieving a partial effect on the second-line therapy with ramucirumab with FOLFIRI regimen in a 74-year-old patient with HER2-negative gastric adenocarcinoma while registering rapid progression after 4 courses of first-line chemotherapy in XELOX regimen. Tolerability of the second line was acceptable: asthenia grade 1, stomatitis grade 1-2, neutropenia grade 3 were observed, so the irinotecan dose was reduced to 165 mg/m2. By June 2021, there were 10 28-day cycles of treatment, which is ongoing. The duration of disease control in the second line therapy was 11+ months, of which 9+ months – on the background of FOLFIRI regimen drug therapy with ramucirumab.

Metastatic breast cancer occupies a leading position in the structure of mortality among women with oncological diseases worldwide. At the same time, the control of metastatic disease remains a significant problem for clinical oncology despite the improvement of early screening indicators, as well as the introduction of targeted therapy in clinical practice. An increase in the tumor stemness and the epithelial-mesenchymal transition in the primary tumor leads to the plasticity of the tumor cell. This is realized in the progression of the disease, resistance to the therapy and the appearance of distant metastases. Numerous signaling pathways, including PI3K/APK, STAT3, Wnt, Hedgehog, and Notch, play a key role in maintaining cellular plasticity in breast cancer. Understanding the cellular mechanisms of breast cancer cell plasticity with the development of multidrug resistance is a prerequisite for the development of effective therapeutic strategies against metastatic breast cancer in late-line therapy. The article presents an overview of the current understanding of the biological mechanism of the metastatic cascade and resistance to therapy. It is from the point of view of the plasticity of the tumor cell and the increase in the stemness of the tumor that the resistance to treatment is considered. The effectiveness of the representative of Ixabepilone was analyzed in the case of its use in the late-line therapy of hormone-receptor-positive breast cancer with multidrug resistance.

Endocrine therapy in combination with inhibitors of cyclin-dependent kinases 4/6 in first lines is the current standard of treatment of metastatic ER positive Her2 negative breast cancer. After progression on several lines of endocrine therapy according to current principles we apply sequential lines of monochemotherapy. If possible non-toxic agents are prefered in order to maintain high quality of life. The special role in this context may play oral agents, when regular visits in clinic and intravenous injection are not needed. The efficacy of oral vinorelbine is well explored, unfortunately the standard dosage regimen сan have quite high especially hematologic toxicity. The metronomic dosing regimen is believed to be as effective as the standard, but is less toxic. In addition, the anti-angiogenic properties of the metronomic mode are described. Taking into account the increasing use of combination of endocrine therapy with CDK4/6 inhibitors in first treatment lines, it is extremely important to study the efficacy and tolerability of various regimens and drugs after progression on combined endocrine therapy. In this article, we represent a clinical case of the use of oral vinorelbine in the metronomic mode in the patient after progression on combination of fulvestrant and palbociclib. Long-term disease control with satisfactory quality of life has been demonstrated.

Personalized therapy is starting to play an increasing role in modern approaches to the treatment of oncological diseases. The previously existing uniform standard for each malignant disease is expanded with new options and treatment possibilities, depending on each specific clinical situation. That increases the  effectiveness of  therapy and helps to control the  disease. A  separate niche in the individual approach to anti-tumor treatment is occupied by targeted therapy of malignancies. There are a lot of mutations that can lead to the emergence of malignant neoplasms. So of all that multitude of choices the individual approach to a patient helps to select the mutations that are most likely to be found in a given patient. The research in the area of the c-MET mutation has allowed it to occupy its niche as a therapeutic target. The identification of this mutation is not included in the routine set of analyses performed for a patient with diagnosed lung adenocarcinoma. But expanding the panel of molecular testing would increase the detectability of this mutation and, as a result, improve the quality of treatment for this category of patients. This clinical case describes the experience of treatment of an elderly patient with lung adenocarcinoma, in whose tumor tissue a MET mutation was detected.