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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.

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. 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.

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.To determine urinary biomarkers of tubular and podocyte damage in patients receiving treatment with antiangiogenic drugs.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.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.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.Обоснование. Антиангиогенные препараты широко используются в онкологической практике и направлены на торможение ангиогенеза. Несмотря на высокую противоопухолевую эффективность, их применение может быть ограничено нефротоксичностью, в связи с чем актуальным остается поиск ранних биомаркеров повреждения почек, которые позволили бы сохранить благоприятный профиль безопасности терапии. Цель. Определить мочевые биомаркеры тубулярного и подоцитарного повреждения почек у больных, получающих лечение антиангиогенными препаратами. Материалы и методы. В исследование вошли пациенты (n=50), получавшие внутривенные анти-VEGF-препараты (афлиберцепт, бевацизумаб, рамуцирумаб) в различных схемах химиотерапии. Концентрации канальцевых маркеров повреждения KIM-1 (Kidney Injury Molecule-1) и NGAL (Neutrophil Gelatinase-Associated Lipocalin), а также маркера гипоксии HIF-1 (Hypoxia-Inducible Factor 1-alpha) в образцах мочи определяли методом иммуноферментного анализа до лечения и в течение 8 нед терапии. Для оценки факторов риска повреждения почек проводили логистический регрессионный анализ с включением основных клинико-лабораторных показателей. Результаты. Снижение расчетной скорости клубочковой фильтрации по формуле CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Formula) 60 мл/мин на 1,73 м2 на 8-й неделе лечения отмечено у 42% больных. Повышение содержания NGAL, KIM-1, HIF-1 и нефрина в моче в течение первых 2 нед терапии прогнозировало развитие почечного повреждения к 8-й неделе наблюдения. При построении ROC-кривых установлена высокая чувствительность и специфичность этих мочевых показателей в качестве прогностических маркеров. Среди клинико-лабораторных показателей независимыми неблагоприятными прогностическими факторами нефротоксичности стали исходное снижение расчетной скорости клубочковой фильтрации, наличие в анамнезе артериальной гипертензии, нарастание концентрации в моче KIM-1 и HIF-1 в течение первых 2 нед терапии. Заключение. Предиктором почечного повреждения при лечении антиангиогенными препаратами оказалось раннее повышение NGAL, KIM-1 и HIF-1 в моче в течение первых 2 нед от начала терапии.

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.

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.

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.

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.To assess early clinical and laboratory manifestations and risk factors for nephrotoxicity of antiangiogenic drugs.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).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.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.Обоснование. Антиангиогенные противоопухолевые препараты, направленные на блокирование сигнального пути сосудистого эндотелиального фактора роста, могут вызывать различные нежелательные явления, среди которых почечное повреждение. Оценка риска нефротоксичности позволяет разработать оптимальные подходы к лечению и обеспечить относительную безопасность терапии. Цель. Оценить ранние клинико-лабораторные проявления и факторы риска нефротоксичности антиангиогенных противоопухолевых препаратов. Материалы и методы. В исследование вошли 50 пациентов, получавших антиангиогенные препараты в составе противоопухолевой химиотерапии. Оценивали демографические показатели, индекс массы тела, цифры артериального давления, тип антиангиогенного препарата, сопроводительную терапию. До начала лечения и в динамике в течение 8 нед с помощью критерия Фридмана оценивали уровень гемоглобина, тромбоцитов, шистоцитов, D-димера, лактатдегидрогеназы сыворотки крови, а также суточной протеинурии и креатинина сыворотки крови и расчетной скорости клубочковой фильтрации (СКФ) по CKD-EPI. Для оценки факторов риска нефротоксичности и артериальной гипертензии (АГ) проводили линейный регрессионный анализ. Результаты. Медиана возраста пациентов составила 46 [3457] лет, 22 (44%) мужчины и 28 (56%) женщин. АГ развилась у 52%, снижение СКФ у 42% наряду со снижением гемоглобина и повышением лактатдегидрогеназы на 2-й неделе терапии. Число шистоцитов и тромбоцитов достоверно снизилось к 8-й неделе терапии. Факторами риска нарушения функции почек на фоне лечения антиангиогенными препаратами стали исходное снижение СКФ80 мл/мин, повышение D-димера, уменьшение гемоглобина к 8-й неделе лечения. Факторами риска формирования АГ на фоне терапии оказались исходное снижение расчетной СКФ80 мл/мин и отсутствие профилактической антикоагулянтной терапии. Заключение. Ранними признаками нефротоксичности антиангиогенных противоопухолевых препаратов являлись снижение СКФ и развитие АГ. Независимыми факторами риска нефротоксичности стали исходное снижение СКФ, повышение D-димера и уменьшение гемоглобина на 8-й неделе лечения, в то же время профилактическое применение антикоагулянтной терапии снижало этот риск в нашем исследовании. Данные изменения можно рассматривать в рамках тромботической микроангиопатии.

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