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The classification of breast cancer (BC) by immunohistochemical phenotypes is widely used in routine clinical practice. However, the genetic profile of the tumor does not always correspond to the pathomorphological one, which can significantly affect the prognosis and predict the effectiveness of therapy in BC. This literature review examines the effectiveness of endocrine therapy depending on the internal subtype of BC, and also presents data on the effectiveness of CDK4/6 inhibitors in these subgroups. It has been shown that during metastasis, the tumor acquires a more aggressive subtype (for example, it switches from luminal to HER2-E or basal-like), which can be stopped when using CDK4/6 inhibitors: the change of the internal subtype passes into a more favorable group.

Background. The use of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in combination with endocrine therapy is a key initial treatment for advanced luminal HER2-negative (HR+/HER2-) breast cancer. The approval studies MONALEESA-2 and 7 demonstrated the efficacy and safety of ribociclib in combination with aromatase inhibitors as a first-line treatment in post- and premenopausal patients. In the Phase lllb CompLEEment-1 study, the same treatment regimen was evaluated in an extended patient population in terms of both safety and efficacy. The article presents an analysis of data from a subgroup of patients from Russia. Materials and methods. The study included 129 patients from Russia who met the inclusion criteria for the CompLEEment-1 study. The primary endpoint was the incidence of adverse events (AEs) at a median follow-up of 25.4 months. Secondary endpoints were median progression-free survival, objective response rate, and disease control. Results. The efficacy and safety results of the therapy in the subgroup of patients from Russia were consistent with the general population of patients included in CompLEEment-1. The incidence of AEs requiring dose adjustment or treatment interruption was 58.1%, and the permanent discontinuation rate was 15.5%. The most frequently reported treatment-related AEs grade 3 or higher were neutropenia and transaminase increased. Conclusion Data obtained in a subgroup of patients from the Russian Federation confirm the safety and tolerability of ribociclib in an extended population of patients with HR+/HER2- breast cancer in settings close to the real world.

Background. Prior to the introduction of new agents — immune checkpoint inhibitors — for inoperable and/or metastatic melanoma (IMM), chemotherapy outcomes were generally poor. The median (Me) overall survival (OS) in IMM was no more than 6-9 months, and the Me of progression-free survival (PFS) was about 2 months. The introduction of immune checkpoint inhibitors and targeted therapy changed the prognosis for the life of IMM patients dramatically. The development, studies, and approval of a new original PD-1 inhibitor, prolgolimab, in Russia in 2020 prompted the professional community to conduct a prospective observational study in the Russian Federation to assess its real-world efficacy and safety. Aim To evaluate the real-world efficacy and safety of prolgolimab in patients with IMM. Materials and methods. From October 2020 to October 2022, 700 patients with IMM receiving prolgolimab in real clinical settings in oncological institutions of various levels in the Russian Federation were included in the study. The main inclusion criteria were: pathology-confirmed diagnosis of melanoma; metastatic and/or inoperable type; use of prolgolimab outside of clinical trials; and signed informed consent. Objective response rate in the general population and the Intention-to-treat and Per Protocol populations was considered the main criterion for evaluating the efficacy of therapy, and the safety criterion was the incidence of grade 3-4 adverse events (AEs). PFS and OS rates were also assessed. Statistical analysis was performed using the SPSS 25.0 software package. Results. The objective response rate for the Per Protocol population (with radiographic assessment available) was 42% (n=235/559). Disease progression was reported in 26.7% (n=149) of patients, stabilization in 31.3% (n=175), and disease control in 73.3% of patients with IMM, regardless of the line of therapy. At the follow-up Me of 12 months (0-36), PFS for all patients regardless of the line of therapy was 8 months (95% confidence interval [Cl] 6.537-9.463), 6-month PFS was 55%, and 12-month PFS was 41%. OS Me for all included patients was 32 months, 6-month OS was 82%, and 12-month OS was 69%. Depending on the line of therapy, the OS Me was: line 1 - not reached, line 2-30 months (95% Cl 16.007-43.993), line 3 and subsequent- 22 months (95% Cl 14.264-29.736); p=0.736. According to the CTCAE 5.0 general terminology criteria for AEs, a total of 136/693 (19.6%) AEs of varying degrees were reported, in particular: grade 1-2 - 105/693 (15.2%), grade 3-4 - 25/693 (3.6%), unknown grade - 5/693 (0.7%), as well as one fatal case (0.1%) due to thromboembolism in the vascular center with an unclear (according to the investigator's assessment) relation with prolgolimab. Conclusion The results obtained at 12 months of follow-up confirm the high efficacy and satisfactory tolerability of prolgolimab in patients with IMM in real-world practice, regardless of the line of therapy and other characteristics.

Background. Exocrine pancreatic insufficiency (EPI) occurs in most patients with advanced pancreatic cancer (PC) and even more often when a tumor is localized in the head of the pancreas. However, insufficient attention is paid to the diagnosis of EPI and assessment of nutritional status, which negatively affects the results of treatment. Materials and methods. One hundred fifty eight patients with primary diagnosed locally advanced and metastatic PC were included in the retrospective study. We used the calculation of the odds ratio with 95% CI with an assessment of the p value using the Pearson ÷2 test to compare the incidence of clinical and laboratory parameters of nutritional status with values below the lower limit of normal (LLN) depending on the location of the tumor in the pancreas. Results. Fecal elastase test was performed in only 19 (12%) patients. In this group, the incidence of EPI was 73.6%. Pancreatic enzyme replacement therapy in the minimal sufficient dose was prescribed in 17.1% of the general cohort. The level of hemoglobin, erythrocytes and albumin below the LLN was found in patients with the tumor in the pancreatic head, respectively, 2.742 (95% CI 1.27–5.92), 3.788 (95% CI 1.554–9.232) and 9.767 (95% CI 1.255–76.027) times more often than in patients with cancer in the body-tail of the pancreas. In patients with the tumor in the pancreatic head, the lower levels of hemoglobin (median 125 g/l vs 132 g/l, respectively), erythrocytes (4.19 mil/μl vs 4.51 mil/μl), total protein (69.6 g/l vs 71.5 g/l), and albumin (40.1 g/l vs 42 g/l), as well as the values of nutritional indices: prognostic nutritional index, nutritional risk index, hemoglobin, albumin, lymphocyte and platelet ratio index, and prognostic immune nutritional index were observed. Conclusion. Diagnosis and treatment of EPI remains inadequately attended. The values of nutritional status parameters in patients with PC in the head are lower than in patients with a tumor in the body-tail of the pancreas, which reflects the contribution of EPI.

NTRK-fusion positive tumors are a rare finding, but targeted therapy demonstrates persistent and sustained systemic and intracranial responses to entrectinib. This resolution proposes algorithms for diagnosing NTRK translocations in various solid tumors and discuses clinical data on the efficacy and safety of entrectinib.

Background. Modern breast cancer chemotherapy regimens (BC) consider individual patient parameters and ranges of cardiotoxic doses. However, clinicians often record clinical and laboratory-instrumental signs of cardio- and vasculotoxicity in patients, which emphasizes the high importance of searching for markers of early toxic response. Aim. To study the characteristics of the response of arterial stiffness on the background of anthracycline-containing chemotherapy to determine potential markers of vasculotoxicity in BC patients. Materials and methods. 20 women with a BC were included. The patients received 4 cycles of chemotherapy in the doxorubicin + cyclophosphane (AC) regimen with an interval of 23 weeks, then they were injected with paclitaxel weekly for 12 injections, or docetaxel once every 3 weeks. All patients underwent TTE, arterial stiffness determination by the "gold standard" method and using volumetric sphygmography before the start of treatment, after the completion of the anthracycline component and after the end of taxanes. Results. The average age of the patients was 45.55.31 years. After completing the course of anthracyclines, there was a significant increase in heart rate (from 65.69.3 to 73.310.1 beats/min.), a decrease in SBP (from 122.69.9 to 116.512.3 mmHg) and DBP (from 78.98.5 to 76.28.6 mmHg), a decrease in carotid femoral pulse wave velocity (cfPWV) (from 9.321.41 to 7.851.57 m/s), CAVI index on the left (from 6.780.81 to 6.50.88), the velocity of the cardio-ankle pulse wave on the right and left (from 6.70.6 to 6.50.7 m/s; from 7.00.6 to 6.30.8 m/sc, respectively). After the completion of the taxane, there was a tendency to increase these indicators, however, they remained significantly lower compared to the values before the start of treatment. Conclusion. A comparative analysis of arterial stiffness indicators at different stages of chemotherapy showed a more pronounced reaction of cfPWV, CAVI, cardio-ankle pulse wave to the administration of anthracyclines, which presumably may be associated with concomitant hemodynamic restructuring.

Background. Currently available data on the efficacy and indications for neoadjuvant chemotherapy in patients with primary resectable pancreatic cancer are contradictory and not clearly defined. Aim. To conduct a comparative assessment of the effectiveness of neoadjuvant chemotherapy and primary surgical treatment followed by adjuvant chemotherapy in patients with primary resectable pancreatic cancer. Materials and methods. In our study, the efficacy of neoadjuvant chemotherapy was retrospectively evaluated in 45 patients and in 153 patients with primary surgical treatment and subsequent adjuvant chemotherapy. Results. With a median follow-up of 41.7 months. Both, recurrence free survival in the group of patients receiving neoadjuvant chemotherapy followed by surgical treatment (n=33; 73%) and in the group with surgical treatment and subsequent adjuvant chemotherapy (13.9 and 19.5 months; p=0.35) and overall survival (28.4 months vs 33.7 months; p=0.29) were no different. The CA level of 19.9500 IU/ml in the neoadjuvant chemotherapy group was observed in 20 (44.4%) patients. At the same time, surgical treatment was performed only in 11 (55%) patients. At the same time, at the CA 19.9 level 500 IU/ml, at the end of neoadjuvant chemotherapy, surgical treatment was not performed in only 3 (12%) patients (p=0.005). Conclusion. The long-term results of treatment of patients with primary resectable pancreatic cancer, whose first stage was neoadjuvant chemotherapy, practically do not differ from the group whose treatment began with surgery. Treatment of patients with an initially high (500 IU/ml) level of CA 19.9 is preferable to start with neoadjuvant chemotherapy. Patients who may have doubts about the likelihood of adjuvant chemotherapy (general condition, social adaptation, place of residence), it is also preferable to start treatment with neoadjuvant chemotherapy. It is necessary to change the algorithm of examination of patients, especially those with a level of CA 19.9500 IU/ml, to exclude a greater prevalence, for example, performing diagnostic laparoscopy to exclude metastases in the peritoneum.

Pancreatic cancer (PC) is a serious public health problem. The mortality rate of patients with PC remains one of the highest among cancers. Early diagnosis of PC is challenging, so it is often diagnosed in the later stages. Current treatment approaches, including surgery, neoadjuvant and adjuvant chemotherapy, chemoradiotherapy, and supportive care, have demonstrated improved outcomes. A significant problem remains exocrine pancreatic insufficiency (EPI) in patients with PC, which requires enzyme replacement therapy. However, this is not given due attention in the Russian literature. This review addresses the survival trends of patients with PC, current therapies, and enzyme replacement therapy as an integral part of supportive care and improvement of nutritional status; also, the issues of routing patients with PC are addressed. It is emphasized that the diagnosis and treatment of EPI are mandatory to improve and maintain the nutritional status and quality of life; failure to treat EPI renders antitumor treatment ineffective.

An increase in the median progression-free survival when using cyclin-dependent kinase 4/6 inhibitors in combination with aromatase inhibitors led to high expectations from the analysis of the overall survival of patients with HR+/HER2- metastatic breast cancer. Of the three drugs in the group, the final data were obtained in the MONALEESA-2 and PALOMA-2 studies, while a statistically significant difference in median overall survival was achieved only with the use of ribociclib. The review discusses possible factors that could affect the final results of the presented studies. The effect of ribociclib on the value of OS in clinically unfavorable prognostic subgroups (for example, patients with visceral metastases) and on progression-free survival depending on the expression of molecular genetic factors that worsen patient survival (such as Rb, p16, Ki-67, CDKN2A, CCND1, ESR1) was analyzed.The combination of ribociclib and aromatase inhibitors has proven to be an advantage in the treatment of patients with HR+/HER2- metastatic breast cancer in terms of increasing both progression-free survival and overall survival. Efficacy has been proven in subgroups with clinical and molecular adverse prognostic factors.

Background. Novel agents immune checkpoint inhibitors fundamentally changed the prognosis for life in patients with metastatic and/or inoperable melanoma. The development, studies, and approval of a new original PD1 inhibitor in Russia in 2020 prompted the professional community to conduct a prospective observational study in the Russian Federation to assess the real-world efficacy and safety of prolgolimab, as real-world patients differ from the refined population in clinical trials. Aim. To evaluate the real-world efficacy and safety of prolgolimab in patients with metastatic and/or inoperable melanoma. Materials and methods. From October 2020 to October 2022, the study enrolled 700 patients with metastatic and/or inoperable melanoma receiving prolgolimab in real clinical settings in oncological institutions of various levels in the Russian Federation. The main inclusion criteria were: pathology-confirmed diagnosis of melanoma, metastatic and/or inoperable type, use of prolgolimab outside of clinical trials, and signed informed consent by the patient. Objective response rate (ORR) was considered the main criterion for evaluating the efficacy of therapy, and the safety criterion was the incidence of grade 34 adverse events. Statistical analysis was performed using the SPSS 20.0 software package. Results. The ORR for patients with skin melanoma treated with prolgolimab in the first line therapy (n= 207/337) was 48.3% (n=100), the disease stabilization was reported in 30.4% (n=63), and progression in 21.3% (n=44) of patients. There were no significant differences in response to therapy between patients with/withoutBRAFmutation, although ORR was higher in patients withBRAFmutation: the ORR for patients withBRAFmutation was 57.9% (n=33), and forBRAFnon-mutated patients, 44.4% (n=52;p=0.222). At a median follow-up of 5 months, the median PFS was 10 months (95% confidence interval 7.3512.64). The incidence of grade 34 treatment-related adverse events according to CTCAE 5.0 was 2% (n=12), and 12% (n=82) for grade 12 adverse events. Conclusion. The results confirm the high efficacy and satisfactory tolerability of prolgolimab in patients with metastatic and/or inoperable melanoma in real-world settings. There were no significant differences in ORR between patients with or withoutBRAFmutation.

Metastatic luminal B HER2-negative breast cancer (HR+/HER2- mBC) occupies a leading place in the global structure of morbidity and mortality among women. The current gold standard of first-line treatment is the combination of CDK4/6 inhibitors with aromatase inhibitors, among which ribociclib with letrozole is distinguished. According to the MONALEESA-2 study, the addition of ribociclib to letrozole significantly increased the median overall survival to 63.9 months, reducing the risk of death by 24%. The safety profile of the combination is manageable, and the development of adverse events led to the interruption of therapy only in 7.5% of cases. A study of the actual clinical practice of CompLEEment-1 also confirmed the safety and effectiveness of the combination. Maintaining and improving the quality of life is one of the main tasks in the treatment of patients with HR+/HER2- mBC. According to the MONALEESA-2 study, the addition of ribociclib significantly affects the maintenance of quality of life and leads to a decrease in the intensity of pain syndrome. The published data allowed us to assign a combination of ribociclib and letrozole 4 points on the ESMO-MCBS scale. The safety of long-term use of the combination in the first line of treatment illustrated by clinical observation. The patient's progression-free survival during therapy was 40 months, which significantly exceeds the data of the MONALEESA-2 and CompLEEment-1 studies. The maximum effect (partial response according to RECIST 1.1 -40%) achieved after 24 weeks and persisted for 24 months. Clinically, the patient noted a decrease in the severity of the pain syndrome after 8 weeks of therapy. Against the background of therapy, it was possible to maintain the quality of life without sacrificing antitumor efficacy.

Background. Antiangiogenic drugs are widely used in oncological practice and are aimed at inhibiting angiogenesis. Despite the high antitumor efficacy, their use may be limited by nephrotoxicity, and therefore the search for early biomarkers of kidney damage remains relevant, which will preserve a favorable safety profile of therapy. Aim. To determine urinary biomarkers of tubular and podocyte damage in patients receiving treatment with antiangiogenic drugs. Materials and methods. The study included patients (n=50) who received intravenous anti-VEGF drugs (aflibercept, bevacizumab, ramucirumab) in various chemotherapy regimens. Concentrations of tubular damage markers KIM-1 (Kidney Injury Molecule-1) and NGAL (Neutrophil Gelatinase-Associated Lipocalin), hypoxia marker HIF-1 (Hypoxia-Inducible Factor 1-alpha) in urine samples were determined by enzyme-linked immunosorbent assay (ELISA) before treatment, and during 8 weeks of treatment. To assess the risk factors for kidney damage, a logistic regression analysis was performed with the inclusion of the main clinical and laboratory parameters. Results. A decrease in the calculated GFR of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Formula) of less than 60 ml/min per 1.73 m2 at week 8 of treatment was noted in 42% of patients. An increase in NGAL, KIM-1, HIF-1 and nephrin in urine during the first two weeks of therapy predicted the development of renal damage by the 8th week of follow-up. When constructing ROC-curves, the high sensitivity and specificity of these urinary indicators as prognostic markers were established. Among the clinical and laboratory indicators, independent unfavorable prognostic factors of nephrotoxicity were an initial decrease in eGFR, a history of hypertension, an increase in the concentration of KIM-1 and HIF-1 in urine during the first two weeks of therapy. Conclusion. The predictors of renal damage in the treatment with antiangiogenic drugs were previously an increase in NGAL, KIM-1 and HIF-1 in urine during the first two weeks after the start of therapy.

Background. Cisplatin is widely used in modern oncological practice. Despite high efficacy treatment with cisplatin is conjugated with high risk of nephrotoxicity. Approximately one third of patients develop renal disfunction after first injection of cisplatin. In clinical practice serum creatinine elevation is used as a marker of renal damage, which is observed after failure of 50% of kidney function. That is why the finding of early biomarker of nephrotoxicity is still an issue. NGAL and KIM-1 are markers of renal damage, the predictive value of which has been described in cardiac surgery and resuscitation practice: an increase in the concentration of these markers in urine precedes the development of renal damage, both ischemic and direct toxic. Aim. To evaluate the role of NGAL and KIM-1 in urine as early markers of cisplatin nephrotoxicity. Materials and methods. The study included 50 patients treated with cisplatin in combination with fluoropyrimidines or paclitaxel. Prior to treatment and over a period of 8 weeks, the Friedman test was used to assess blood pressure, plasma creatinine, potassium, urea levels, daily proteinuria, urine NGAL and KIM-1 levels, and glomerular filtration rate (GFR). ROC analysis was used to assess the prognostic significance of NGAL and KIM-1 in the development of nephrotoxicity. Results. There was a statistically significant increase in the level of urea (=17.7; df 4, p=0.001), potassium (=42; df 4, p0.001), a decrease in GFR (=32.3; df 4, p0.001), the appearance of proteinuria (=50.4; df 4, p0.001). The concentration of NGAL and KIM-1 increased already one week after the start of cisplatin therapy, reaching a maximum by 8 weeks (=200; df 4, p0.001). The appearance of NGAL at a concentration of 10.743 ng/ml and KIM-1 at a concentration of 182.4 pg/ml in the first week after administration of cisplatin allows predicting the development of nephrotoxicity by the 8th week with high sensitivity (90.91%) and specificity (94.87%), AUC 0.96. Conclusion. The appearance of NGAL and KIM-1 in urine already in the first week of treatment allows predicting the development of nephrotoxicity a decrease in GFR of less than 60 ml/min by the 8th week of therapy with high sensitivity and specificity. Both biomarkers can be considered early prognostically significant.

The consensus on the prevention and correction of rash in patients with HR+ HER2- metastatic breast cancer treated with alpelisib was developed by the experts of the Russian Society of Clinical Oncology and dermatovenerologists. PIK3CA mutation is a poor prognostic factor for HR+ HER2- metastatic breast cancer. Alpelisib demonstrates efficacy in patients with PIK3CA mutation, but treatment might be associated with adverse events that include rash. All-grade rash was reported in 35.6% patients in SOLAR-1 trial (n=284). According to the published real-world data, for Russian population (n=19) all-grade rash was reported for 37% patients. The consensus contains practical recommendation on management of patients with rash of different grade.

Background. Anti-angiogenic anticancer drugs that block the vascular endothelial growth factor signaling pathway can cause renal damage. Assessment of the risk of nephrotoxicity allows developing optimal treatment approaches and ensuring the relative safety of therapy. Aim. To assess early clinical and laboratory manifestations and risk factors for nephrotoxicity of antiangiogenic drugs. Materials and methods. The study included 50 patients who received antiangiogenic drugs in different regimens of chemotherapy. Demographic factors, body mass index, blood pressure levels, type of antiangiogenic drug, and concomitant therapy were assessed. Before treatment and over a period of 8 weeks, the levels of hemoglobin, number of platelets and schistocytes, D-dimer levels, serum lactate dehydrogenase (LDH) levels, as well as daily proteinuria and serum creatinine and eGFRCKD-EPI were assessed. Linear regression analysis was performed to assess risk factors for nephrotoxicity and arterial hypertension (AH). Results. The median age of patients was 46 [3457] years, 22 (44%) men and 28 (56%) women. AH developed in 52%, a decrease in eGFR in 42%, along with a decrease in hemoglobin levels and an increase in LDH levels at 2 weeks of therapy. The numbers of schistocytes and platelets significantly decreased by 8 weeks of therapy. Risk factors for impaired renal function during treatment with antiangiogenic drugs were an initial decrease in GFR less than 80 ml/min/1.73 m2, an increase in D-dimer levels, and a decrease in hemoglobin levels by 8 weeks of treatment. The risk factors for AH during therapy were the initial decrease in eGFR less than 80 ml/min/1.73 m2 and no prophylactic anticoagulant therapy. Conclusion. Early signs of nephrotoxicity of antiangiogenic anticancer drugs were a decrease in eGFR and AH. The independent risk factors for nephrotoxicity were the initial decrease in eGFR, an increase in D-dimer levels, and a decrease in hemoglobin levels at 8 weeks of treatment, while the prophylactic use of anticoagulant therapy reduced this risk in our study.

Triple-negative breast cancer is 1024% of all cases of breast cancer and is characterized by the absence of estrogen, progesterone, and HER-2 receptors in the tumor. The therapy of this illness is a difficult clinical case. In contrast to hormone-positive and HER-2-positive phenotypes, in which we successfully use targeted drugs (antiestrogens and anti-HER-2 drugs), for triple-negative breast cancer we have not had such targets for a long time. Thus, despite the impressive results of immunotherapy of triple-negative breast cancer, there remains a fairly large group of patients with negative PD-L1 status, for whom it is necessary to develop other treatment strategies. One of the approaches in the treatment of malignant tumors includes not the impact on tumor cells, but the process of angiogenesis. Antiangiogenic drugs have positively proven themselves in the treatment of a large number of malignant tumors but are underestimated for breast cancer (including triple-negative phenotype). The use of bevacizumab in combinations with cytostatic drugs in breast cancer therapy (including triple-negative breast cancer) has been studied in a large number of clinical trials but was undeservedly forgotten in some countries due to the revoked FDA registration. This review presents the role of bevacizumab in the treatment of patients with triple-negative breast cancer and suggests the conditions when the administration of this drug is justified and leads to better results.

Breast cancer (BC) is a malignant tumor originating from the epithelium of the breast tissue. There is no single etiological factor in the development of breast cancer. In 310% of patients with breast cancer, the development of the disease is associated with the presence of mutations in the breast cancer gene (BRCA) 1, BRCA2, CHEK, NBS1, TP53. In other patients, breast cancer is sporadic.

Breast cancer is still the leading cause of death in patients with malignant tumors. Among women with breast cancer, standard combination chemotherapy with anthracyclines and taxanes reduces mortality from this disease by about one third compared to patients not receiving chemotherapy and is the standard for neoadjuvant or adjuvant chemotherapy of breast cancer. Understanding the patterns of tumor growth has made it possible to improve the current paradigms of the treatment of early forms of breast cancer and to use dose-dense chemotherapy regimens to achieve better treatment results. Nowadays, chemotherapy in a dose-dense regimen for breast cancer is the preferred option in all world and Russian clinical guidelines. However, the use of such chemotherapy regimens significantly increases the incidence of side effects, primarily febrile neutropenia. The appearance of more effective methods of supportive care, particularly short-acting and long-acting granulocyte colony-stimulating factor, in clinical practice has made it possible to use dose-dense chemotherapy regimens to increase the effectiveness of the treatment.

The virtual forum on the diagnosis and treatment of PIK3CA-mutated metastatic breast cancer was held on 16th October 2020. The French and Russian oncology experts shared information and exchanged experience concerning the application of the first PI3K inhibitor alpelisib.

Background. Breast cancer (BC) maintains the leading position in the structure of the morbidity and mortality from malignancies. Triple-negative BC (TNBC) is the most aggressive subtype among all types of BC. The adequate and timely initiation of neoadjuvant chemotherapy (NAC) determines the further prognosis of the disease in case of early and locally advanced TNBC. Patients over 60 years old are the special subgroup, but it has not been previously considered separately. Aim. To determine the efficacy of NAC and survival in elderly patients with stages II to III TNBC. Materials and methods. Since 2014, 92 patients with histologically verified early and locally advanced TNBC have received NAC, followed by surgery ± adjuvant therapy. NAC was conducted under the following scheme: cisplatin 75 mg/m2 on day 1, paclitaxel 80 mg/m2 on days 1, 8 and 15 of 28-day cycle, for six cycles. After the end of NAC, patients underwent surgery and a follow-up assessment of the degree of therapeutic pathomorphism in the primary tumor and regional lymph nodes. Further on, the correlation analysis was carried out between clinical characteristics and the degree of therapeutic pathomorphism. Results. We analyzed the data from the 92 patients, 22 (23.9%) patients of them were in older age group. At the time of disease diagnosis, the patients older than 60 years of age had a greater involvement of regional lymph nodes (N3: 40.9% vs. 20.0%, p

Aim. Eribulin is an active cytostatic, associated with a wide range of mechanisms of antitumor effects, but eribulin efficiency and safety in patients with breast cancer (BC), associated with cerebral metastases are still poorly understood. Materials and methods. We analyzed the combined Russian experience of eribulin application in BC patients associated with brain metastases; the analysis included 459 Russian women with advanced BC who had received at least 2 course of eribulin during the period from 2014 to 2018; 35 of 459 patients had brain metastases (40.0% - luminal HER2-negative subtype, 31.4% - triple negative subtype and 28.6%h - HER2-positive BC). The median age was 52 years (39 - 80 years of age). In most cases, the patient had two or more metastatic brain lesions (68.6%; the median was - 3); brain radiotherapy was used in 62.8% of patients before eribulin treatment and in 5.8% of patients was held stereotactic radiation therapy during eribulin chemotherapy. We analyzed the efficiency of eribulin application (the therapy continued until disease progression, the development of unacceptable toxicity, or impossibility to apply the drug for any other reason). Results. The results showed that clinical efficacy (objective response rate + stabilization of disease lasting for more than 6 months) was 48.6%: partial response - in 20% of patients and stabilization of disease - 62.9%; tumor growth control was in 82.9%. Median PFS in all group of patients with brain metastases was 4.1 months and was similar to median PFS in patients who received radiotherapy before eribulin treatment or without eribulin - 4.1 vs 3.47 months; p=0.798. Conclusions. The application of eribulin in BC patients with brain metastasis are absolutely justified, the drug demonstrates the efficiency in a retrospective analysis in a Russian population. The determination of the optimal algorithm for the treatment of patients with metastatic BC associated with brain metastasis requires a multidisciplinary approach and further research.

Aim. The aim of the study is to examine the efficacy and safety of eribulin in HER2-negative metastatic breast cancer (BC) in Russian clinical practice. Materials and methods. The analysis included 459 patients with advanced BC from 44 federal and municipal medical clinics in Russia and received at least 2 courses of treatment with eribulin in accordance with the registered indications for drug. The average age of women was 56 years (between 29 and 81 years), 83% of patients had HER2-negative tumor subtype (49.9% - luminal BC and 33.1% - triple-negative BC) HER2-positive biological tumor subtype was registered in 17% of patients. Visceral metastases were diagnosed in 73% of patients and three-zone and multiple zone metastases were diagnosed in 41.6% of cases. The median number of prior lines of therapy in patients with disseminated disease was 2; anthracycline and taxane chemotherapy was applied in 94.3% of patients, and 38.1% of patients were recived CT plus capecitabine. Standard treatment regimen with eribulin was cotinuing (1.4 mg/m² as a 2-5-minute intravenous infusion administrated on days 1, 8 of a 21-day cycle) until disease progression, unacceptable toxic effects, or impossibility of the drug administration for any other reason. We estimated the efficacy and safety of treatment with eribulin in Russian patients with HER2-negative BC. Results. Objective response rate was achieved in 20.5% of cases, complete response rate was in 3.2%, partial - 17.3%, and the stable disease rate was marked in 52.7% of women, and in 19.7% of these cases was prolonged more than 6 months. The frequency of objective response was higher in luminal BC group compared with triple-negative BC: 23.5% vs 15.8%; tumor growth control 76.9% vs. 67.8%, respectively; p