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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 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.

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.