Assessment of safety and tolerability of subcutaneous trastuzumab in patients with HER2-positive early breast cancer: Results of an open-label, randomized, multicenter, phase IIIB ESCAPE trial.

AIM: To assess the safety and tolerability of subcutaneous (SC) trastuzumab (Herceptin) administered either with a single-use injection device (SID) or manually from a vial using a hand-held syringe. METHODS: The ESCAPE trial (NCT02194166) included 90 women aged 18 years or older with HER2-positive early breast cancer who underwent surgical treatment and completed (neo) adjuvant chemotherapy and radiotherapy (if indicated). Patients enrolled in the study were first subjected to 4 cycles of trastuzumab IV (8 mg/kg loading dose followed by 6 mg/kg maintenance dose, q3w) prior to being randomized into groups: [A] SC trastuzumab (fixed dose 600 mg, q3w) administered through a hand-held syringe followed by 7 cycles of SC trastuzumab administered with an SID or [B] the reverse sequence. RESULTS: Patient-reported outcomes revealed that 78 (94.0 % [95 % CI: 90.4-99.0]) out of 83 patients preferred SC trastuzumab over IV trastuzumab, among whom 28 patients indicated a strong preference. Sixteen out of 17 HCPs (94.1 %) were very satisfied with the use of SC trastuzumab, while 1/17 (5.9 %) remained uncertain. The mean time spent for IV vs. SC trastuzumab administration, including pre- and postinjection procedures, was 93.8 and 22 min, respectively. A total of 49 (54.4 %) patients reported 164 AEs. CONCLUSIONS: In this trial, SC trastuzumab was preferred over IV trastuzumab. The duration of SC trastuzumab administration was significantly shorter than that of IV trastuzumab, saving patients and HCPs time. Safety and efficacy results were consistent with other published trials and were not associated with any new safety signal.

Characteristic Mutational Damages in Gastric and Colorectal Adenocarcinomas.

INTRODUCTION: Gastric and colorectal adenocarcinomas are prevalent malignancies characterized by mutations in genes such as p53, RAS, and MDM2, which play crucial roles in tumorigenesis and cancer progression. Understanding the specific mutational patterns and their implications in these cancers was essential for identifying potential therapeutic targets. AIM: To identify the nature of mutational disorders in the p53, p21Waf1, RAS and MDM2 genes, depending on the degree of cell differentiation by adenocarcinomas of the gastrointestinal tract. METHODS: Genomic DNA was isolated from 200 samples of stomach tissue and 233 samples of colon and rectum adenocarcinomas. A total of 433 samples, including gastric adenocarcinomas, colon and rectum adenocarcinomas and adjacent tissues, were collected. RESULTS: Genomic DNA was isolated, and mutational analysis of p53, RAS (HRAS, KRAS, NRAS), and MDM2 genes was performed using polymerase chain reaction, gel electrophoresis, and restriction enzyme analysis. The deletion of p53 exon-intron 5-6, as well as HRAS 12 and HRAS 61 mutations, were detected in 78% of poorly differentiated adenocarcinomas. The deletions of p53 exon-intron 7-9 - in 100% of moderately differentiated adenocarcinomas and 50-60% of adjacent tissues. The loss of WAF1 gene expression was registered in almost 90% of poorly differentiated adenocarcinomas and 20% of adjacent tissue samples. The KRAS and NRAS mutations in almost 63.9% of studied colon and rectal samples indicated autonomous cell growth. This explains the aggressive and metastatic growth of tumours and the ineffectiveness of growth factor inhibitors in colorectal cancer. Finding ways to influence specific substitutions in RAS genes could prevent and eliminate uncontrolled invasive tumour growth. CONCLUSION: By identifying specific gene mutations and differences in genetic markers, the study provided insights for the development of targeted diagnostic methods and personalised treatment strategies, ultimately improving the clinical outcomes in the field of oncology.

Five-year overall survival of patients with advanced bladder cancer in Kazakhstan: OSURK registry study.

BACKGROUND: The goals of the OSURK registry study were to assess 5-year overall survival (OS) in patients with metastatic urothelial cancer diagnosed in 2017 in Kazakhstan and collect data on the use of various treatment options in routine clinical practice. METHODS: Patients with newly diagnosed metastatic bladder cancer (BC) were retrospectively identified in the national register of Kazakhstan (ERCP) between January 2017 and January 2018. ERCP is the biggest register in the country and includes patient data from 17 regions. Investigators collected patient information and processed records online on the following anonymised data: demographical characteristics, received treatment and outcomes. Patients were included in the study if mBC was confirmed histologically and they had at least one visit to the cancer center during the follow-up period. The outcomes of interest were overall survival (OS), patient characteristics and treatment patterns. RESULTS: Totally 480 adult patients with metastatic BC were included. Mean number of patients in one region per year was 28.2. Median age at diagnosis of mBC was 70.0 years (range, 30-100). Patients were predominantly male (81.3%), histological subtype of BC (urothelial carcinoma, etc.) was determined in 41%. Overall, 187 (39%) patients received systemic therapy for metastatic disease. Platinum-based chemotherapy was prescribed in 147 (76.8%) patients who received systemic treatment. The majority of treatment was with cisplatin (N=132, 70.6%). Sixty-four (13.3%) patients received ≥2 treatment lines. After median 60.5 months of follow-up the 5-year OS in patients with metastatic BC was 2.7%. The 1-, and 3-year OS rates were 31.0% and 9.8%, respectively. Median OS from the start of treatment was 7.3 months (95% CI 6.5-8.1). CONCLUSIONS: The results of the OSURK study indicate the need for further implementation of innovative drugs in real practice in order to significantly increase the OS of patients with metastatic BC.

Natural killer cell activity level in colorectal cancer screening in an average risk population.

Introduction: Increased natural killer cell activity (NKCA) is linked to reduced risk of colorectal cancer (CRC). Several prior studies have investigated the association of NKCA and the incidence of CRC in high-risk subjects. The aim of our study was to investigate NKCA sensitivity in diagnosing advanced neoplasia (AN) and CRC in an average risk population. Material and methods: NKCA was assessed by an enzyme-linked immunosorbent assay (ELISA) blood test in average risk subjects with a range of 25-2500 pg/ml set for ELISA. NKCA higher than 200 pg/ml was defined as negative. The performance of NKCA was evaluated using measures such as sensitivity, specificity, negative and positive predictive values (NPV, PPV), clinical utility index, etc. In addition, odds ratios for developing CRC using logistic regression models were calculated. Results: NKCA was evaluated in 354 average risk individuals (mean age: 58.5 years; 36.2% male). The diagnostic accuracy of NKCA for CRC and AN was 75.5% and 72.3% respectively, with 96.4% NPV. The NKCA test demonstrated a good negative clinical utility index for CRC and AN (0.664 and 0.741, respectively). Individuals with low NKCA had 6.84 times higher odds of having CRC (95% CI: 2.31-20.27; p < 0.001). NKCA was higher in men vs. women (548.5 pg/ml vs. 500.0 pg/ml) and lower in smokers (412 pg/ml vs. 544 pg/ml), non-exercisers (413 pg/ml vs. 653.5 pg/ml), alcohol users (389 pg/ml vs. 476 pg/ml), and native Kazakhs and other Asian ethnic groups (446 pg/ml vs. 514 pg/ml). Conclusions: A high NKCA level has potential ability to rule out CRC and AN in an average risk population.

Prevalence, incidence, and mortality rates of breast cancer in Kazakhstan: data from the Unified National Electronic Health System, 2014-2019.

Background: Although there are numerous sources of epidemiologic information on breast cancer in Kazakhstan, none of them have specifically examined the burden of this disease. Therefore, this article aims to provide an overview of the breast cancer prevalence, incidence, mortality, and distribution and changes over time in Kazakhstan based on nationwide large-scale healthcare data from the National Registry in order to encourage more research on the impact of various diseases at the regional and national levels. Methods: The study cohort included all adult women older than 25 years who were diagnosed with breast cancer in any clinical setting of the Republic of Kazakhstan during the period of 2014-2019. The data were extracted from the Unified Nationwide Electronic Health System (UNEHS) to get an overview of descriptive statistics, incidence, prevalence, and mortality rate calculations and the Cox proportional hazards regression model. All survival functions and factors associated with mortality were tested for significance. Results: The cohort population (n = 55,465) comprised subjects with the age at the diagnosis of breast cancer from 25 to 97 years, with a mean of 55.7 ± 12.0 years. The majority of the study population belonged to the age group 45-59 years, which is 44.8% of the cohort. The all-cause mortality rate of the cohort is 16%. The prevalence rate increased from 30.4 per 10,000 population in 2014 to 50.6 in 2019. The incidence rate varied from 4.5 per 10,000 population in 2015 to 7.3 in 2016. Mortality rates were stable and high in the senile age patients (75-89 years old). Breast cancer mortality was positively associated with women who had been diagnosed with diabetes, HR 1.2 (95% CI, 1.1-2.3), whereas it was negatively associated with arterial hypertension, HR 0.4 (95% CI, 0.4-0.5). Conclusion: Overall, Kazakhstan is experiencing an increase in the incidence of breast cancer cases, but the mortality rate has started to decline. The switch to population mammography screening could reduce the breast cancer mortality rate. These findings should be utilized to help Kazakhstan determine what cancer control priorities should be utilized, including the need to implement efficient and affordable screening and prevention programs.

Trends of Colorectal Cancer Prevalence in Kazakhstan Related to Screening.

We carried out an analysis of the total incidence of colon cancer throughout Kazakhstan. Retrospectively, according to the regional reports on endoscopic screening, the study showed an increase in the age-related incidence of colorectal cancer (CRC) cases from 2004-2008 to 2009-2014. The peak of morbidity in both periods was noted in the age category of >70 years. The indicators of the territorial distribution of CRC incidence make it possible to divide the regions into areas with low or high rates of CRC. Specific indicators showed newly diagnosed cases of CRC stages I, II, III, and IV in 2004-2018. The incidence rates of stages I and II showed a two-fold increase (35%-67.4%) and the incidence of stage IV showed a decline from 19.3% to 13.1% and of stage III from 45.7% to 19.5% from 2004 to 2018, respectively. An analysis of CRC incidence throughout Kazakhstan showed an increase in the overall incidence. Since population-based CRC screening was introduced in 2011, the morbidity was found to increase for stages I and II.

Overall survival in patients with metastatic renal cell carcinoma in Russia, Kazakhstan, and Belarus: a report from the RENSUR3 registry.

BACKGROUND: Real-world data describing outcomes of treatment among metastatic renal cell carcinoma (mRCC) patients are limited and heterogeneous. AIM: RENSUR3 registry study assessed real-world data on the use of therapies in mRCC and overall survival (OS) in Russia, Kazakhstan, and Belarus. METHODS: Patients were included in the retrospective multicenter registry study. To be eligible, patients were required to have mRCC diagnosed from January 2015 to January 2016. Anonymized data were collected through an online registry. The outcomes of interest were patient characteristics, treatment patterns, and OS. RESULTS: 1094 mRCC patients were identified. Mean age was 62.3 (SD, 11.2) years. Four hundred and forty-four (41%) patients were 65 years and older. Primary tumor has not been removed in 503 (46%) patients. Subtype of RCC based on WHO classification (clear-cell or other) has been reported in 402 (37%) patients. In total, 595 (54.4%) patients received systemic therapy for metastatic disease. 58% of elderly patients (≥65) were not treated compared to 37% of younger patients. Cytokines and targeted therapy were used in 298 (50.1%) and 297 (49.9%) of 595 treated patients, respectively. Median OS was 11.9 months (95% CI 10.9-12.9). The 1- and 3-year OS rates were 49.6% and 19.3%. CONCLUSIONS: Half of patients received no systemic therapy or had only cytokines for mRCC in Russia, Kazakhstan, and Belarus, which doubtless negatively affected OS in this population. Novel therapies should be considered as life prolonging and a priority.

Epidemiology of Prostate Cancer in the Republic of Kazakhstan.

BACKGROUND: The incidence and mortality from prostate cancer in most native Asian populations remain low although a gradual increase is observed over the last years. METHODS: The statistical analysis of official data on prostate cancer mortality and morbidity was performed for the whole country and for Pavlodar Region. RESULTS: The increase in the incidence of prostate cancer among the population of Kazakhstan is observed, which may be attributed to the introduction of screening program based on serum PSA. Still, the crude incidence rates in Kazakhstan are below world indices. Over the last few years, the decreasing prostate cancer mortality is observed that might be influenced by early diagnosis. The age-standardized incidence rates show that the majority of prostate cancer cases occur in advanced ages (70 years and older). CONCLUSION: More research is needed to determine the risk factors for prostate cancer, as well as ethnic and geographical trends for the population of Kazakhstan.