Introduction. HCC is a challenge for clinical oncology. 1-year mortality for advanced HCC accounts for 66% in the

Russian Federation. The results obtained in the combined Atezolizumab and Bevacizumab therapy in the advanced HCC cases are reported.

Objective. To assess efficacy and safety of anti-VEGF/PD-L1 Atezolizumab plus Bevacizumab therapy in 20 unresectable HCC patients.

Materials and methods. This analyses carried out in Blokhin National Cancer Research Centre included 20 patients with unresectable HCC treated with the first-line Atezolizumab (1200 mg) and Bevacizumab (15 mg/kg) once every 21 days, 11 patients participated into the global open-label phase 3 trial IMbrave150 23,24 (NCT03434379 / YO40245; Sponsor of study F. Hoffmann-La Roche, Ltd). The therapy was discontinued in cases of tumor progression or intolerant toxicity. The efficacy was evaluated according to RECICT 1.1 criteria. The results were analyzed and visualized on the basis of statistical calculations R 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria). Descriptive statistics for quantitative variables are presented as mean (standard devia[1]tion) and median (lower and upper quartiles), for categorial variables as absolute number of observations (%). To compare quan[1]titative variables (AFP level) in progress Wilcoxon test was used. The differences were considered statistically significant with p < 0.05. Overall survival (OS) and progression-free survival (PFS) data were evaluated according to Kaplan-Meier methodology.

Results and discussion. Median follow up was 9.3 months (quartile 1–3: 6.0–14.4) for 20 patients. Median progression free sur[1]vival was 14.9 months (lower bound, 95% CI, 9.0 months, upper bound NA). 12–month progression-free survival rate from the fixed date of the initial therapy was 56.2% (95% CI: 34.4–91.8%). One-year survival for 20 patients from the fixed date of the initial therapy was 70.0% (95% CI: 49–100). Treatment resulted in objective response (partial regression) in 3 (15%) pts, stable disease in 13 (65.0%) and progression in 4 (20.0%), patients. 35% of patients experienced Gr 3–4 adverse events with Gr3–4 arterial hypertension was the most common one in 20%. In 1 case esophageal varices hemorrhage Gr3 took place.

Conclusion. Atezolizumab and Bevacizumab seems to be highly efficient in advanced HCC.

This article analyzes approaches of the treatment of ALK-positive non-small cell lung cancer (NSCLC). Despite the relatively small percentage of patients with ALK-gene rearrangements, identification of this mutation is very important. The most effective treatment for patients with ALK translocation is the use of ALK inhibitors, which significantly improve survival rates compared to standard chemotherapy. Crisotinib was the first drug approved for the treatment of advanced ALK-positive NSCLC. However, the soon emerging resistance during crizotinib therapy and the inevitable progression of the disease led to the development and introduction into clinical practice of new ALK inhibitors, such as ceritinib and alectinib, the latter of which is currently the best choice for the first-line treatment of metastatic ALK-positive NSCLC. Brigatinib and lorlatinib are drugs that are expected to be registered in the Russian Federation as soon as possible. Lorlatinib, a third generation of ALK and ROS1-kinase inhibitor, allows achieving a high rate of intracranial disease control, and is also effective against acquired resistance mutations during therapy with crizotinib and other ALK inhibitors. The toxicity profiles of each ALK inhibitor are extensively studied and controlled. The wider application of molecular genetic testing and the accumulation of data on resistance mutations will make it possible to correct selection of the next line of treatment. It also became possible to use a combined regimen of immunochemotherapy as the next line of treatment in case of progression against the background of targeted therapy. The available information allows 

The treatment of advanced hormone- receptor-positive (HR+) breast cancer (BC) is a rather difficult task due to the emergence of resistance to the standard treatment regimen – endocrine therapy. This circumstance has led to the investigation of the role of the tumor microenvironment in the tumor response and the realization of the treatment efficiency. A new class of antitumor drugs – inhibitors of cyclin- dependent kinases 4/6 (CDK 4/6) in combination with endocrine therapy demonstrates the efficiency in prolonging the progression free survival and significantly delays the time of cytotoxic therapy administration. In this case,an additional mechanism of tumor regression, besides inhibition of cell cycle of tumor cells is the influence on the cellular component of the tumor microenvironment. Thus, according to preclinical data and results of clinical studies, an increase in the immunogenicity of the tumor and the activation of the antitumor immune response was established. This unique mechanism can be used as a strategy to increase the efficiency of antitumor drugs prescribed in later lines, as well as to increase sensitivity to immune checkpoint inhibitors. The article presents an analysis of the clinical efficiency of an aromatase inhibitor in combination with a CDK 4/6 - inhibitor Abemaciclib in male with HR-positive breast cancer. At the same time, the appointment of aromatase inhibitors in the presented clinical case is very justified due to the possible genetic violation of the metabolism of sex hormones, taking into account the pathophysiological bases of male gynecomastia. Despite the lack of an objective response to combination therapy, the patient has a long-term stabilization. This may be due to an increase in the immunoreactivity of the tumor, a cumulative effect with the development of senescence of tumor cells and subsequent apoptosis. Also, it is very likely that after the use of the CDK 4/6 inhibitor Abemaciclib, cytotoxic chemotherapy drugs will show greater effectiveness due to the actively altered immunoreactivity of the tumor microenvironment. 

Introduction. Simultaneous inhibition of programmed cell death-1 (PD-1)/PD-L1 immune checkpoint and VEGF/VEGFR signaling has a  synergistic antitumor effect in  preclinical models. This article presents the  results of  the  phase III study JAVELIn Renal 101 (NCT02684006), as well as the experience of using this combination in real clinical practice.

Materials and methods. In 2016, the JAVELIn Renal 101 randomized phase III trial (NCT02684006) was launched to compare the efficacy of avelumab and axitinib versus sunitinib in previously untreated patients with metastatic renal cell carcinoma (mRCC). The study included 886 patients randomized 1:1: avelumab + axitinib group (442 patients) and sunitinib group (444 patients). A total of 560 (63.2%) patients had PD-L1 positive tumor expression (PD-L1+): 270 in avelumab + axitinib group and 290 in sunitinib group.

Results and discussion. Median progression-free survival was 13.8 versus 7.2 months, respectively (RR for disease progression or death 0.61; 95% CI). In the general population median progression-free survival was 13.8 months versus 8.4 months, respectively (RR 0.69; 95% CI 0.56 to 0.84; p < 0.001). Among those with PD-L1-positive tumor status, the objective response rate was 55.2% in avelumab + axitinib group and 25.5% in the sunitinib group; the median follow-up period for overall survival was 11.6 months and 10.7 months; 37 vs 44 patients died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab + axitinib group and in 99.3% in the sunitinib group. Experience of using the combination of avelumab with axitinib in real practice was presented by British researchers in another study. The study included 44 patients with mRCC who had not previously received drug therapy. The mean follow-up period was 6.9 months (range 0.8–13.5 months). The mean age was 68 years (range 48–81). The obtained clinical data confirmed the results of the JAVELIn Renal 101 study with the high efficacy of avelumab + axitinib combination in patients with mRCC in the first line of drug therapy.

Conclusion. The avelumab + axitinib combination is effective in mRCC treatment regardless of ECOG, PD-L1 status and risk group. This combination shows objective rate and PFS increase both in general and PD-L1+ population. 

Prostate cancer (PC) is one of the leading causes of cancer death in the male population. Currently, the pathogenesis of prostate cancer has been studied in sufficient detail, which makes a successful radical treatment possible in most cases. However, in about 30% of patients traditional methods (e.g., radical prostatectomy, radiation therapy, androgen deprivation therapy – ADT, etc.) are ineffective, and castration- resistant (CRPC) and metastatic (mPC) types of РС are developing. Due to the advances in modern molecular oncology, various “workarounds”, genetic and epigenetic combinations, that allow РС to progress despite the absence of androgenic stimulation, are known nowadays. A personalized approach in oncology, which gradually becomes one of the standards for mCRPC therapy, allows not only to identify specific mutations, but also to select the most effective therapy for them in the most correct way. Now the most promising groups of the drugs for mCRPC treatment are poly(ADP-ribose)-polymerase (PARP) inhibitors, immune checkpoint inhibitors, and prostate- specific membrane antigen (PSMA) targeted therapy. This article attempts to summarize the current data on PARP inhibitors. The drugs of this group are especially effective for malignant neoplasms with mutations in the BRCA 1/2 genes, and successfully used in ovarian, breast and pancreatic cancer. They have been approved for the treatment of mCRPC a not so long ago. The advent of personalized companion tests has made the treatment of mCRPC more precise. Nowadays studies on the effectiveness of PARP inhibitors for mCRPC with other genetic and epigenetic changes, as well as in combination with other therapeutic agents, are notably actual. 

Introduction. mBRAF mCRC has the aggressive phenotype. The incidence of such mutation in Europe and the USA is around 8–14%, in Asian countries – 4–8%. The purpose of this population-based study was to determine the incidence and identifying prognostic factors in pts with mBRAF mCRC in Russia. 

Materials and methods. A multicenter retrospective analysis of clinical data and treatment results of pts with mBRAF mCRC was 
performed. The main method for determining mutations was a PCR. The main efficacy endpoint was progression free survival (PFS) at the 1 st line. Multivariate analysis was performed using Cox regression model. 
Results and discussion. 437 out of 8648 pts (5.17%) with a known mutational status had mBRAF (V600). Clinical data were collected from 131/437 (30%): the right-sided primary tumor – in 58,6%, left-sided – in 19%, rectum – in 21,4%. ORR in pts with mBRAF was 31%, median PFS was 6 months. We didn’t revealed any differences between FOLFOXIRI and doublets (XELOX/
FOLFOX or XELIRI/FOLFIRI) in terms of PFS (HR 0.9, 95% CI 0.49–1.52, р = 0.6) and OS (HR 1.5, 95% CI 0.61–4.1, р = 0.35) in pts with mBRAF. 
Conclusions. The incidence of mBRAF gene in the population of pts with mCRC in the Russia is low and we found a high incidence of localization of the primary tumor in the rectum. We didn’t reveal any differences between the usual duplets and standard regimen for such mutation - FOLFOXIRI in term of 1 st line PFS. 

Introduction. Ramucirumab (R) with paclitaxel (PTX) is a global standard for second-line (2L) therapy in advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) get treated with taxanes in the perioperative or 1st line metastatic setting. For those pts the benefit of a combination of R+P is unclear, and many physicians would choose an irinotecan based regimen as 2L. We present data of retrospective analysis from pts with GEA with docetaxel-containing 1st line treated with ramucirumab and paclitaxel (R+PTX) or FOLFIRI (R+FOLFIRI) as 2L in a «real-life» setting.

Materials and methods. We identified 46 docetaxel pre-treated pts from RAMSELGA data-base who received R+PTX (n = 19) or R+FOLFIRI (n = 27) as 2L.

Results and discussion. The median progression-free survival (MPFS) and median overall survival (MOS) for pts treated with R+PTX were 7.9 (95% ДИ: 6.2–9.7) and 18.1 (15.1–21.2) months, and those for pts treated with R+FOLFIRI – 7.1 (95% ДИ: 4.3–9.9) and 15,8 (12.1–19.5) months, respectively. There are no significant differences. Main adverse events of special interest were hypertension grade (gr) 1-2, epistaxis gr 1-2: 78.9% и 21.1% in R+PTX group and 29.6% и 22.2% in R+FOLFIRI group, there were serious adverse events in R+FOLFIRI: hypertension gr4 (1 pt), gastrointestinal haemorrhage (1pt), gastrointestinal perforation gr 3 (1pt), death of stroke (1 pt) and gastrointestinal haemorrhage (1pt).

Conclusion: docetaxel pre-treated pts seemed to derive pronounced benefit from FOLFIRI-Ram, providing a rationale for a phase III trial.

Introduction. Main oncologic indicators such as morbidity, mortality, early detection of malignant tumors, one-year mortality rate, noticeably differ not only among the countries but also among the regions of one country, and even more among the territories of one region. Oncological service informatization let us evaluate the target indicators in each territory unit of the region at any given time and to reveal the actual problems.

The object of the work was to find out the differences in one-year oncological mortality rate among the territories of Sverdlovsk Region and to reveal the relation of it with the distribution of stages of detected oncological cases and with the availability of anticancer drug therapy (ADT).

Materials and methods. Indicators of one-year mortality rate, distribution of stages of new cases, specialized treatment performed, were received from the regional oncological informational system ONCOR. The analysis of data on 32758 ADT courses conducted to patients from 60 districts of the Sverdlovsk region in the first 6 months of 2020 was carried out.

Results and discussion. The number of courses held varied from 33 to 1 213, unique schemes – from 9 to 267. We analyzed the accessibility of ADT based on the relative indicators such as density of ADT (the ratio of the number of courses carried out to patients from a given territory to those registered in each territory) and diversity of ADT (the ratio of unique patterns of ADT in patients from a given territory to the number of registered patients in each territory). The density of ADT ranged from 11,8 to 108,3 courses per 100 registered patients, the variety of PLL – from 0,7 to 10 schemes per 100 registered patients. A relationship was revealed between the distribution by stages of detected cases of malignant neoplasms and one-year mortality, between the percentage of stage IV and the density of ADT. The density of ADT influenced the one-year mortality rate even with the leveling of the effect of the proportion of stage IV.

Conclusion. The regional oncological system allows to demonstrate territorial differences in the indicators of the oncological service and the availability of specialized treatment. The density of ADT influenced the one-year mortality rate. The received information about the fulfillment in medical organizations at the place of patient’s residence the oncological dispensary appointments should be considered when making changes to regional orders for routing patients with malignant tumors. 

Introduction. Patients with cancer are more likely to develop thromboembolic complications, and the occurrence of thrombosis complicates the course of anticancer treatment and worsens the survival rate of cancer patients. Low molecular weight heparins (LMWH) is the first choice for the treatment of cancer-associated thrombosis, as there is extensive evidence on the efficacy and safety of LMWH in cancer patients based on current knowledge.

Materials and methods. There were 190 cancer patients under our supervision at various stages of complex treatment. Of these, 70  patients with acute thrombosis and pulmonary embolism  (PE) who received therapeutic doses of  enoxaparin  sodium. Assessment of hemostasis parameters was carried out using an automatic analyzer. The patients underwent duplex angioscanning of the vessels of the lower extremities.

Results and discussion. The use of enoxaparin sodium in cancer patients with thrombosis reduced the intensity of intravascular coagulation with a decrease in the concentration of fibrinogen and markers of intravascular coagulation. According to the ultrasound study, venous thrombosis was not detected, or recanalization of the vessel lumen occurred, in no case did PE develop. Eight patients retained high levels of D-dimer (> 2 μg/ml) and von Willebrand factor, which were unfavorable prognostic signs. In these patients, recurrence of venous thrombosis was observed, which required a more prolonged and persistent treatment of thrombotic complications.

Conclusion. Enoxaparin sodium is an effective and safe drug for the treatment of thrombosis in oncology. 

Introduction. Liposarcoma is the most common retroperitoneal sarcoma. The majority of retroperitoneal liposarcomas are represented by highly differentiated and dedifferentiated liposarcomas. To date, clinical practice has not developed an effective method of the stratification of patients with RLPS into prognostic groups to determine the tactics of patient management.

Objective. To develop a method for stratification of patients with retroperitoneal well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcomas into prognostic groups. Materials and methods. A retrospective study included 111 patients with WDLPS and 74 patients with DDLPS. The staging of the disease was carried out according to the modified TNM-classification, the analysis of survival was performed depending on the histological type of retroperitoneal liposarcoma (RLPS), the effect of age on overall survival (OS) was evaluated in WDLPS and DDLPS. Further, multivariate Cox regression analyzes were performed to assess the independent factors influencing the prognosis of patients. Then, we developed a methodology for stratification of patients into prognostic groups. OS and recurrence-free survival (RFS) were analyzed in accordance with it.

Results and discussion. OS and RFS were statistically significantly worse in DDLPD compared with WDLPS (p = 0.000; log-rank test). At the same time, the results of the work demonstrated the absence of a statistically significant difference in OS and RFS depending on the degree of malignancy of DDLPS. In case of WDLPS and DDLPS, significant differences in OS were achieved only between groups of patients whose age was (at the time of the initial detection of RLPS) under 60 years and older (p = 0.008; p = 0.026; logrank test). Thus, the borderline value of the age of patients, which affects the prognosis, was determined – 60 years. OS and RFS were statistically significantly different between all prognostic groups (p = 0.000; log-rank test). The highest OS was achieved in the group with a “favorable prognosis”, while the shortest OS was in the group with the extremely poor prognosis (p = 0.000; log-rank test). The median OS in the “favorable prognosis” group was 225 (95% CI, 174, 276) months; in the “intermediate prognosis” group – 130 (95% CI, 115, 145) months; in the “poor prognosis” group – 90 (95% CI, 79, 101) months; in the “extremely poor prognosis” group – 22 (95% CI, 15, 29) months. The highest RFS was achieved in the group with a “favorable prognosis”, while the shortest RFS was achieved in the group with an “extremely poor prognosis” (p = 0.000; log-rank test). The median RFS in the “favorable prognosis” group was 80 (95% CI, 65, 95) months; in the “intermediate prognosis” group – 47 (95% CI, 33, 61) months; in the “poor prognosis” group – 26 (95% CI, 24, 28) months; in the “extremely poor prognosis” group – 10 (95% CI, 6, 14) months.

Conclusion. The proposed method for stratification of patients with RLPS into prognostic groups demonstrates an adequate distribution of patients and the reliability of intergroup differences in the survival rate. 

The PI3K / AKT / mTOR pathway plays a key role in the regulation of cell proliferation, growth and survival. It was found that the PIK3CA mutation, an oncogene encoding the catalytic isoform of PI3K kinase p110α, is one of the most frequent somatic mutations in breast cancer: it is found in about 20-50% of all cases, most often in the ER + HER2 subtype. Studies have shown that the presence of the PIK3CA mutation is associated with an increased risk of recurrence, progression, or death. A deeper understanding of the role of the PIK3CA mutation in the growth and survival of cancer cells has led to the development of targeted therapeutic agents aimed at directly inhibiting the PI3K pathway. Alpelisib is the only PI3K inhibitor to date that has successfully passed clinical trials and is approved for the treatment of ER + HER2– metastatic breast cancer in patients with the PIK3CA mutation who have previously received hormonal therapy. The article presents a clinical case of treatment with Alpelisib, discusses in detail the issues of drug efficacy, including after CDK 4/6 inhibitors, as well as tolerance and management of adverse events. Alpelisib not only expands the treatment options for patients with the PIK3CA mutation, but is also a clear example of therapy personalization. 

Checkpoint inhibitors, as well as their combinations, are increasingly included in the daily practice of the oncologist. However, given the mechanism of action, its use may be associated with immune side effects that can complicate the clinical course and prognosis of patients. As the number of reported indications for the administration of PD-1, PD-L1, CTLA-4 inhibitors increases, the rate of reports of rare complications associated with immunotherapy increases. Among the complications, it is worth highlighting the group of autoimmune endocrinopathies. Such complications of immunotherapy as hypophysitis, hypo- and hyperthyroidism are quite common, are relatively easy to correct and usually do not lead to discontinuation of therapy. The mechanisms underlying immune damage to target organs remain poorly understood. Primary adrenal insufficiency is a rare and potentially life-threatening complication that, due to non-specific symptoms, may be recognized too late. The development of adrenal insufficiency was noted in only 0.7% of patients in randomized clinical trials. To date, there is no single tactic for identifying and treating this complication. The management of such patients is possible only by a multidisciplinary team that includes an endocrinologist. We present a clinical case of the development of adrenal insufficiency on the background of combined chemo-immunotherapy and the results of the patient’s treatment after its resolution. 

When we talk about hereditary ovarian cancer, we usually mean BRCA – associated cancer. Detection of hereditary ovarian cancer is important for the prevention of cancer in blood relatives of mutation carriers, and also makes it possible to use PARP inhibitors as maintenance therapy in BRCA – associated ovarian cancer.Due to the widespread introduction of modern molecular genetic technologies and the expansion of the diagnostic panel, mutations in genes other than BRCA 1/2 have begun to be detected in individuals with suspected hereditary ovarian cancer. Lynch’s syndrome is one of the most common and studied hereditary cancer syndromes. Interest in this syndrome in recent years is due to the emergence of the possibility of using checkpoint inhibitors – pembrolizumab and nivolumab for the treatment of colorectal cancer, stomach and endometrial cancer. To date, the definition of mutations in the genes of the MMR – system in ovarian cancer has not yet been applied in practice. Proband is a 69-year-old female with stage IIIC ovarian cancer at the time of diagnosis. The family history is burdened by 2 cases: lung cancer in the father and pancreatic cancer in the mother after the age of 60 years. Despite the advanced oncological process at the time of diagnosis, the start of combined treatment with 5 courses of neoadjuvant chemotherapy, incomplete cytoreduction, the patient’s overall survival during the follow-up period was 92 months. The clinical course of the disease was characterized as BRCA-associated ovarian cancer: long overall and relapse-free survival, long free-ofcharge interval with several relapses of more than 6 months; burdened family history; response to therapy with platinum and gemcitabine. However, when testing a patient with platinum-sensitive relapse by PCR, no mutations in the BRCA genes 1 and 2 were detected. To search for causal mutations, genetic testing was carried out using NGS technologies at the second stage. A germline mutation in the EPCAM gene involved in Lynch syndrome has been identified.