Pyatigorsk Oncology Center

Purpose: To evaluate the proportion of BRCA1 / 2 mutations in patients with serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum in Russia, to evaluate the percentage of germinal and somatic mutations, to identify the spectrum of mutations in BRCA1 / 2 genes, to evaluate clinical and morphological features of the BRCA-associated ovarian cancer (OC).Patients and methods: The study enrolled patients of 18 years and older with newly diagnosed serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum. Biological material (blood, tumor tissue) was collected, followed by molecular genetic analysis. The method of mutations detecting in the blood were: allele-specific PCR, high-resolution melting (HRM), Sanger sequencing method. Advanced genetic testing included the use of generation sequencing (NGS) and multiplex amplification of ligated probes (MLPA). The collection of clinical data, family history, clinical and morphological characteristics of the tumor was performed.Results: 500 patients were included in the study, the evaluation of BRCA1 / 2 mutations was performed in 496 patients (99,2 %). The frequency of BRCA1 / 2 mutations in the Russian patient population was 28,4 % (n = 141 / 496). The incidence of germinal mutations was 23,5 % (n = 117 / 141), and somatic — 4,8 % (n = 24 / 141). Frequent mutations in the Russian population were identified in 50 % of cases. When analyzing the ethnicity of patients in the Russian Federation BRCA-associated OC was most common in Russian (83,6 %, n = 118 / 141), Ukrainian (4,2 %, n = 6 / 141) and Tatar (3,5 %, n = 5 / 141) women. A family history of cancer was detected in 44 % of patients (n = 62 / 141) with BRCA1 / 2 mutations.Conclusions: Due to the high frequency of germinal and somatic BRCA1 / 2 mutations in the Russian patients it is recommended to conduct the advanced testing methods not only in blood samples but also in tumor tissue.

To level out the nutrient imbalance in diets, patients with carbohydrate and lipid metabolism disorders are prescribed to include specialized low-fat food with increased protein content. In this regard, the development and evaluation of the effectiveness of such products enriched with micronutrients is relevant. The purpose of the research was to evaluate the clinical effectiveness of a specialized fermented milk product for the dietary correction of carbohydrate and fat metabolism disorders. Material and methods. The study involved 40 patients with type 2 diabetes mellitus with concomitant abdominal obesity. The average age was 62.0±1.2 years. The hypocaloric diet (1708 kcal/day) of the patients in the main group (n=20) included daily for 21 days 200 g of a specialized fermented milk product containing 5.0% protein, 0.5% fat, 8.0% carbohydrates, enriched with taurine (0.4 mg%), carnitine (0.3 mg%), manganese, zinc and 12 vitamins. The patients in the control group (n=20) did not receive this product. All patients underwent an anthropometric assessment, bioimpedancemetry, and examined biochemical blood parameters characterizing carbohydrate and lipid metabolism. Vitamin status was assessed by the level of vitamins C, E, D, B12 in the blood serum. Status was evaluated by the serum levels of malone dialdehyde, 8-hydroxy-deoxyguanosine and superoxide dismutase and glutathione peroxidase activity. Results. The study of the clinical efficacy of the specialized fermented milk product showed good tolerability by patients. After 3 weeks of diet therapy, patients in both groups showed statistically significant decreases in body weight, body mass index, body fat mass, waist circumference, serum level of glucose, total and low-density lipoprotein cholesterol. Patients in the main group showed more pronounced positive dynamics of body component composition. There was statistically significant decrease in fluid while maintaining skeletal muscle mass, in contrast to the indices in patients of the control group. The inclusion of the specialized fermented milk product in the low-calorie diet was accompanied by a statistically significant decrease in serum level of malone dialdehyde and 8-hydroxy-deoxyguanosine by an average of 17% from the initial level (p<0.05), and an increase in superoxide dismutase activity by 18.5% (p<0.05), 25(OH)D and vitamin C level by 35 and 51% (p=0.001), respectively, in the absence of index dynamics in patients of the control group. Conclusion. The specialized fermented milk product can be used in diet therapy, including for the purpose of dietary correction of disorders of fat and carbohydrate metabolism, as an additional source of vitamins, trace elements (zinc, manganese), as well as taurine and L-carnitine.

The authors touch upon the development of relations between German and Russian peoples in the process of economic and trade relations emergence between Germany and Russia in the period of the XVI–XVII centuries; describe the generalized experience of adaptation of German settlers in a completely new social environment for them and note the fact of increasing Russian authority in Europe, the origins of which were the search for the foundations of mutual understanding and trust, as well as a fairly long period of rapprochement between Russia and Germany. After the Livonian War, a negative stereotype about Russia developed in the national consciousness of the German population, which served as an impulse for migration sentiments, coupled with a desire to see everything for themselves, considering it a backward country with a slavish population. The authors also consider measures to organize the resettlement of German peasants and attempt to identify problematic issues of the arrangement of their future. In relation to foreigners in medieval Russia, there were numerous restrictions due to the internal political state of the country. In Peter the Great years, with the establishment of business contacts with Germany. But despite the multiple attempts to improve the lives of German society representatives, especially those who arrived in Russia as the first batches of immigrants, they could not adapt to local conditions and returned to their homeland. Some, hoping for the best, remained and were taken out to the citizenship of the Russian emperors.

Abstract Background: Trazimera™ (PF-05280014) is a trastuzumab biosimilar. This multinational, randomized, double-blind, parallel-group study (NCT01989676) compared Trazimera with reference trastuzumab (Herceptin®) sourced from the EU (Herceptin-EU), each plus paclitaxel, in the first-line treatment of HER2-positive metastatic breast cancer (MBC). Equivalence between the two groups was previously demonstrated for the primary efficacy endpoint of objective response rate, evaluating responses achieved by Week 25 and confirmed by Week 33 (Pegram et al, Br J Cancer 2019). Furthermore, using data collected up to 378 days after randomization, there were no notable differences in progression-free survival, overall survival (OS), safety, or immunogenicity. Here, we report additional cumulative safety and OS data collected up to 5 years after the first patient was screened. Methods: Eligible patients were randomized 1:1 to receive intravenous Trazimera or Herceptin-EU, each plus paclitaxel. Randomization was stratified by prior trastuzumab exposure and estrogen receptor status. Trazimera or Herceptin-EU treatment could continue until objective disease progression per RECIST 1.1. In addition to evaluating safety and OS in the overall study population, we assessed safety in the subgroup of patients still ongoing in the study after Day 378 (including only adverse events starting after this time point). We also compared time to discontinuation from Trazimera or Herceptin-EU. Results: Of 707 patients randomized (Trazimera, n=352; Herceptin-EU, n=355), 83 (11.7%) were ongoing in the study as of the data cutoff on February 25, 2019 (Trazimera, n=41 [11.6%]; Herceptin-EU, n=42 [11.8%]). Overall, 637 (90.1%) patients discontinued trastuzumab treatment (Trazimera, n=319 [90.6%]; Herceptin-EU, n=318 [89.6%]). The most frequent reason for discontinuing trastuzumab was objective progression (Trazimera, n=245 [69.6%]; Herceptin-EU, n=245 [69.0%]). Estimated median time to discontinuation from trastuzumab was 12.25 months for Trazimera and 12.06 months for Herceptin-EU (stratified hazard ratio [HR] 1.014; 95% confidence interval [CI] 0.867-1.186; log-rank P=0.569). In total, 58 (16.5%) patients in the Trazimera group and 67 (18.9%) patients in the Herceptin-EU group died. There was no statistically significant difference in OS (stratified HR 0.888; 95% CI 0.624-1.264; log-rank P=0.254). Estimated 2-year survival rates were 82.26% for Trazimera and 77.50% for Herceptin-EU; corresponding estimated 3-year rates were 77.17% and 75.33%. Among patients who received treatment (Trazimera, n=349; Herceptin-EU, n=353), there were no notable differences in incidences of treatment-emergent adverse events (TEAEs; 98.3% vs. 96.6%), grade 3 or higher TEAEs (40.7% vs. 42.5%), or serious TEAEs (19.2% vs. 19.3%). Rates of cardiac failure (1.4% vs. 2.8%), infusion-related reaction (IRR; 9.7% vs. 9.1%), and decreased ejection fraction (13.2% vs. 13.0%) were similar. Comparable proportions of patients had ≥1 occasion of an absolute decrease in left ventricular ejection fraction of ≥16% from baseline (6.3% vs. 5.4%) or ≥10% from baseline and below the lower limit of normal (4.0% vs. 5.1%). In the subgroup ongoing after Day 378 (Trazimera, n=265; Herceptin-EU, n=264), rates of cardiac failure (0.0% vs. 1.1%), IRR (0.0% vs. 0.8%), and decreased ejection fraction (3.4% vs. 4.2%) remained balanced. Conclusion: Long-term safety and OS data were consistent with previous results from this ongoing comparative study of Trazimera and Herceptin-EU, demonstrating no clinically meaningful differences between treatment groups. These results represent the longest known follow-up data reported for a trastuzumab biosimilar study in patients with HER2-positive MBC. Funding: This study was sponsored by Pfizer. Citation Format: Rubi K Li, Oleg Lipatov, Hryhoriy Adamchuk, Vladimir Vladimirov, Eduardo Yanez, Patricia Banchero, Amy Freyman, Fiona Hilton, Alexandra Thiele, Alicia Vana. Trazimera (a trastuzumab biosimilar) in HER2-positive metastatic breast cancer: Long-term safety and overall survival data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-08.

The objective of the present study was to estimate the effectiveness of the new therapeutic modalities for the spa and health resort-based treatment of metabolic syndrome based on the results of the long-term follow-up observations. A total of 100 patients presenting with metabolic syndrome were recruited for the participation in the study. All of them underwent a shortened course of mineral water intake in the combination with the use of the herbal medicinal products. The results of the study give evidence of the more favorable changes in the clinical and instrumental characteristics of the patients with metabolic syndrome treated with the use of the proposed approach in comparison the patients treated by the conventional methods. Moreover, the beneficial effects of the proposed approach persisted during a longer period. The basal treatment given to our patients was supplemented by dietary therapy, therapeutic physical exercise, narzan baths, intake of mineral water having a temperature of 35-37 °С in conjunction with sulphate mineral water (narzan) cooled to 13-15 °С, and a phytococktail. The results of the long-term observations confirmed the enhanced effectiveness of the spa and health resort-based treatment of metabolic syndrome including the therapeutic courses with the intake of cooled narzan mineral water in the combination with phytococktails. This therapeutic modality increased the duration of the favorable changes of various parameters that characterize metabolic syndrome. Specifically, they persisted during 5-6 months after the application of the standard methods, were still apparent within 6-7 months after the two-week course of the treatment with cold narzan and phytococktails, and during 8-9 months when the duration of the treatment course was extended up to 3 weeks.

Cetuximab in combination with an irinotecan‐containing regimen is a standard treatment in patients with KRAS wild‐type (KRAS WT), metastatic colorectal cancer (mCRC). We investigated the addition of the oral MET inhibitor tivantinib to cetuximab + irinotecan (CETIRI) based on preclinical evidence that activation of the MET pathway may confer resistance to anti‐EGFR therapy. Previously treated patients with KRAS WT advanced or mCRC were enrolled. The phase 1, open‐label 3 + 3, dose‐escalation study evaluated the safety and maximally tolerated dose of tivantinib plus CETIRI. The phase 2, randomized, double‐blinded, placebo‐controlled study of biweekly CETIRI plus tivantinib or placebo was restricted to patients who had received only one prior line of chemotherapy. The phase 2 primary endpoint was progression‐free survival (PFS). The recommended phase 2 dose was tivantinib (360 mg/m2 twice daily) with biweekly cetuximab (500 mg/m2) and irinotecan (180 mg/m2). Among 117 patients evaluable for phase 2 analysis, no statistically significant PFS difference was observed: 8.3 months on tivantinib vs. 7.3 months on placebo (HR, 0.85; 95% confidence interval, 0.55–1.33; P = 0.38). Subgroup analyses trended in favor of tivantinib in patients with MET‐High tumors by immunohistochemistry, PTEN‐Low tumors, or those pretreated with oxaliplatin, but subgroups were too small to draw conclusions. Neutropenia, diarrhea, nausea and rash were the most frequent severe adverse events in tivantinib‐treated patients. The combination of tivantinib and CETIRI was well tolerated but did not significantly improve PFS in previously treated KRAS WT mCRC. Tivantinib may be more active in specific subgroups.