Republican Oncological Clinical Dispensary

TPS583 Background: Lenvatinib plus pembrolizumab (Len+P) is an established first-line regimen for metastatic clear cell renal cell carcinoma (mRCC). In the CLEAR study, patients with low tumor burden derived substantial benefit; however, ~20% achieved only stable disease (SD) as best response. In the VOLGA study, outcomes were improved when even a single lesion was irradiated during targeted therapy. We hypothesize that adding stereotactic body radiotherapy (SBRT) to multiple lesions in patients with SD during Len+P therapy will increase the objective response rate (ORR) and potentially improve overall survival (OS). Methods: LASER is a randomized, multicenter, phase 2 study. Eligible patients must have histologically confirmed mRCC, sum of target lesion diameters ≥7 cm, ECOG PS 0–2, and no prior systemic therapy for metastatic disease. All patients receive 12 weeks of induction therapy with Len (20 mg daily) plus P (200 mg Q3W). Imaging is performed per RECIST v1.1 to classify response as complete/partial response, SD, or progression. Patients with SD are randomized 1:1 to: (1) Len+P+SBRT or (2) Len+P alone. In the SBRT arm, up to 3 lesions are selected for irradiation by a multidisciplinary team. The primary endpoint is ORR of non-irradiated lesions after randomization, assessed every 12 weeks per RECIST v1.1. Secondary endpoints include progression-free survival (PFS), OS, response from irradiated lesions, and safety. The study is powered to detect an increase in ORR from 15% (control) to 50% (SBRT arm), with α = 0.05 and 80% power, requiring 27 patients per arm (54 randomized). Total planned enrollment is 150 patients to account for the proportion achieving SD following induction. Clinical trial information: KCRB-092025/2.

Chronic gastroduodenitis (CGD) is considered as a multifactorial pathology, in the etiology of which the leading role is assigned to infection with H. pylori (HP). The issue of symbiotic relationships of HP with other infectious agents, including pathogens of parasitic and fungal nature, is being discussed in the scientific community, but the features of combined lesions are insufficiently described. The aim of the study was to study the frequency of H. pylori and protozoal fungal invasions in chronic inflammatory diseases of the stomach and duodenum, the effect on morphological changes in the mucous membranes of the gastrointestinal tract. Material and methods. 87 patients diagnosed with CGD were examined. The material for the study was biopsies of the gastric mucosa and duodenum 12, faeces. Cytological and immunochromatographic methods were used to identify HP. The staining by Romanovsky-Giemsa was used for detection of the morphological changes in the mucous membranes and the microflora. Parasitoscopic methods were used to identify the protozoa. The results of the study. When studying the microbial composition of the stomach in 87 patients with CGD, the mixed microflora was found, including eukaryotic nature. A preliminary analysis of the results in the group of H. pylori-positive patients (n=57) showed that the association of H. pylori and yeast-like fungi of the genus Candida was found in 29% of cases, the association of H. pylori, yeast-like fungi of the genus Candida and protozoa (G. lamblia) - in 19% of cases. The study of the SOF microflora of patients with CGD showed the presence of more severe forms of morphological changes, in particular, intestinal metaplasia and dysplasia, in H. pylori and fungal-protozoal mixed invasion, than in the absence of infection (p<0.05). A significant difference was noted in the group of H. pylori -positive for the detection of protozoa and fungi of the genus Candida compared with the group of H. pylori-negative patients (p<0.05). Conclusion. The presence of protozoal fungal mixed invasion in H. pylori - associated with the gastroduodenitis can have a potentiating pathogenetic effect on the functions of all parts of the gastrointestinal tract, leading to dysbiotic disorders and the development of a chronic inflammatory process, which requires the development of algorithms for complex diagnosis and correction of dysbiotic conditions.

Background. Adjuvant targeted therapy (ATT) with a combination of dabrafenib and trametinib after radical surgical treatment in patients with stage III skin melanoma (SM) with a BRAF V600 mutation reduces the risk of disease recurrence. The effectiveness of this approach has been demonstrated in randomized clinical trials, and also confirmed in several large non-Russian real-world (RW) studies. Aim. To evaluate, in RW settings, the effectiveness of ATT with a combination of dabrafenib and trametinib after definitive surgical treatment in patients with BRAF V600-positive SM in Russia. Materials and methods. The RATIONALE study is a prospective, non-interventional, multicenter RW study. The follow-up duration for the study was 1 year. Patients with SM older than 18 years who had previously started dabrafenib and trametinib therapy no more than 8 weeks prior to Visit 1 were included in the study. The paper presents results from the analysis of Cohort 1 only (patients who received dabrafenib and trametinib in the adjuvant setting). Results. The cohort included 214 patients with BRAF V600-mutated SM of stages IIIA–D and IV resectable. At the time of therapy initiation, the majority of patients were stage IIIc (54.7%) or IIIb (22.0%). The most common mutation – BRAF V600E – occurred in 66.3% of cases, while the second most common variant – BRAF V600 not otherwise specified – was detected in 31.3%. One-year overall survival for all included patients was 94%, one-year relapse-free survival was 84%, and one-year distant metastasis-free survival was 86%. No previously listed adverse events were reported. Adverse events led to therapy discontinuation in only 11.7% of cases. ATT did not reduce patients' quality of life. In the subgroup analysis, the effectiveness of the combination of dabrafenib and trametinib after removal of distant metastases (equivalent to stage IV resectable) was found, in particular, the one-year relapse-free survival rate was 83%, and the one-year overall survival rate was 100%, which is comparable to these indicators for stage IIIB-D (72–86 and 78–100%, respectively). Conclusion. The effectiveness and favorable safety profile of the combination of dabrafenib and trametinib in ATT after radical surgical treatment was confirmed in a population of Russian patients with SM in the RW settings.

Background. A Russian phase IV observational study was initiated to evaluate the efficacy and safety of lenvatinib with pembrolizumab (Len-Pembro) in patients with advanced renal cell carcinoma (RCC) receiving therapy in real-world practice. This article is based on the results of the third analysis conducted with a median follow-up of 23.1 months and reflects data on the efficacy and safety of Len-Pembro in Russian patients. Aim. To evaluate the real-world efficacy and safety of Len-Pembro in patients with advanced RCC with a median follow-up increased to 23.1 months. The primary outcome of the study was progression-free survival (PFS), the secondary outcomes included overall survival (OS), progression-free survival on next-line therapy (PFS2), objective response rate (ORR), duration of response, as well as safety. Materials and methods. The study included data from 165 patients with verified advanced RCC who received Len-Pembro at 36 centers in the Russian Federation from February 05, 2018 to July 30, 2025. The median age was 60 (20–76) years, and 70.3% of the participants were male. Most patients (74.6%) presented with Karnofsky performance score of ≥80%, metachronous metastases (50.9%) of clear cell RCC (93.3%) in 1 organ (75.2%), and had not received any anticancer treatment (91.0%). The IMDC favorable prognosis group included 40 (24.2%), intermediate – 92 (55.8%), and unfavorable prognosis – 33 (20.0%) patients. The median follow-up reached 23.1 (0.5–72.9) months. A total of 110 (66.7%) patients completed Len-Pembro therapy, and 51 (30.9%) patients received next-line treatment. Results. Median PFS reached 25.8 (95% confidence interval – CI 17.0–34.5) months, 23-month PFS – 52.6%; median OS was 39.9 (95% CI 26.9–52.8) months, 23-month OS – 73.1%; median PFS2 was 33.2 (95% CI 23.4–41.1) months, 23-month PFS2 – 66.9%. The ORR was 49.1%, including 3.0% of complete responses, and the disease control rate was 89.1%. The median duration of response reached 29.7 (95% CI 24.9–34.6) months. The incidence of any adverse events (AEs) was 78.8%, severe AEs occurred in 29.1%, fatal AES – in 1.2%, immune-related AEs – 17.0%, severe immune-related AEs – 6.7%. Conclusion. In real-world practice, with increased follow-up duration, the values of PFS, OS, and PFS2 were comparable to those obtained in the registrational study, with a lower ORR and a satisfactory safety profile of the combination of Len-Pembro in advanced RCC.

Hepatocellular carcinoma is the most common primary malignant neoplasm of the liver, accounting for more than 90% of cases. Before the introduction of targeted therapy, there were virtually no options for the treatment of unresectable HCC. Currently, sorafenib and lenvatinib are registered as first-line therapy for unresectable HCC. The introduction of the combination of atezolizumab and bevacizumab has significantly improved the results of HCC treatment. In the IMbrave 150 study, the median OS was 19.2 months in the atezolizumab and bevacizumab group and 13.4 months in the sorafenib group. The median progression-free survival was 6.9 and 4.3, respectively. The presented clinical observation describes a case of treatment of a patient with unresectable HCC, a large tumor burden and portal vein thrombosis. In the first line of therapy, we considered the combination of atezolizumab and bevacizumab. A rapid response to the therapy was obtained, a complete response was registered after 42 months of therapy with a combination of atezolizumab and bevacizumab. A minimum number of adverse events and satisfactory tolerability were noted. Currently, the patient continues therapy with this combination. Currently, an increasing number of patients receive therapy with atezolizumab and bevacizumab for a long time. Experience is accumulating in real clinical practice of monitoring patients who have been receiving a combination of immunooncologic and targeted drugs for a long time.

Cancer-associated thrombosis (CAT) is one of the most frequent and dangerous complications of malignancies, ranking 2nd among the causes of death in cancer patients. The article presents an overview of current data on the pathogenesis of thrombosis in cancer patients, including the key role of tumor cells, inflammatory cytokines, neutrophil extracellular traps, and dysregulation of hemostasis. CAT epidemiology, individual (age, comorbidities, mobility) and tumor-dependent (location, stage, histology) risk factors, as well as the effect of various types of anticancer therapy, including chemotherapy, surgery, and the use of central venous catheters, are considered. Particular attention is paid to modern approaches to the prevention and treatment of CAT, including direct oral anticoagulants, their advantages over low molecular weight heparins, and data from large randomized trials (CARAVAGGIO and API-CAT). The review includes an analysis of international and Russian clinical guidelines (ASCO, NCCN, RUSSCO), focusing on the need for an individual approach, considering the clinical situation, the risk of bleeding, and drug interactions. The presented data emphasize the importance of timely detection of CAT and rational choice of therapy to reduce the risk of complications and improve the prognosis in cancer patients. The presented data emphasize the importance of timely detection of CAT and rational choice of therapy to reduce the risk of complications and improve the prognosis in cancer patients. In addition, a reduced dose of apixaban (2.5 mg twice daily) after 6 months of therapy was found to be effective in preventing the recurrence of venous thromboembolism and reducing the incidence of clinically significant bleeding compared to the full dose.

Background. Cervical cancer (CC) is among the four most common malignancies among the female population. For a long time, platinum-based chemotherapy was the standard of care and practically the only option available. However, treatment outcomes for patients with metastatic and recurrent CC remained poor. The use of immune checkpoint inhibitors significantly increased progression-free survival and overall survival in this group of patients. Currently, pembrolizumab is a priority option in treating patients with metastatic, persistent, recurrent CC with CPS ≥ 1 and is included in international and Russian clinical guidelines. Aim. To evaluate the efficacy and safety of a pembrolizumab biosimilar (Pembroria®) in patients with metastatic, persistent and recurrent CC in the interim analysis of the PERFECTION observational study. Materials and methods. The study included a group of 51 patients diagnosed with stage IV CC. The treatment efficacy was analyzed using the Fleming method with the objective response rate criterion according to RECIST 1.1. Safety was assessed by the incidence of adverse events (AEs) and serious AEs according to the CTCAE 5.0 toxicity scale. Results. At stage g2, an objective response was reported in 24 (47.1%) patients, which exceeded the target threshold (22 responses). 5 (9.8%) patients experienced immune-mediated AEs, a total of 6 cases, including 1 case of grade 3 AE. The overall objective response rate was consistent with KEYNOTE-826, but the AE rate was lower (34.5% in KEYNOTE-826). Conclusion. Pembroria® has demonstrated efficacy comparable to that of the original pembrolizumab product and an acceptable safety profile. Differences in the incidence of immune-mediated AEs associated with Pembroria® require further study, considering the duration of observation and sample size. The results support using Pembroria® in routine clinical practice.

Chemotherapy is an integral part of drug treatment of patients with metastatic breast cancer (mBC), regardless of the biological subtype of the tumor, and the availability of a large number of effective drug treatment options can significantly increase life expectancy. Intensive neoadjuvant and adjuvant chemo ± targeted therapy, as well as pretreatment for the metastatic form of the disease, can significantly reduce the effectiveness of subsequent lines of chemotherapy, which complicates the choice of treatment options. That is why the results of modern observational studies of real clinical practice are of exceptional value. Ixabepilone is a semi-synthetic analogue of epothilone B, used for locally advanced or metastatic breast cancer when previous therapy is ineffective.The purpose of this study is to evaluate the efficacy and tolerability of ixabepilone alone and in combination with chemoor target drugs in real clinical practice in the Russian Federation.Methods. A multicenter, non-interventional, retrospective study of ixabepilone therapy in routine clinical practice in patients with locally advanced or metastatic breast cancer with ineffectiveness of previous therapy NIRMA (CLO1418141) included 101 patients who received ixabepilone as monotherapy and in various combinations in the 1st and subsequent lines of therapy from 01.01.2021 to 31.12.2023 in 15 oncological institutions of the Russian Federation.Results. The median of previous therapy lines for metastatic disease was 3. Ixabepilone therapy was administered alone (n=58), in combination with capecitabine (n=30), or in combination with trastuzumab (n=13). The median PFS was 5.77 months. [95 % CI 5.31–6.07] The objective response rate was 35.64 % (36/101), including 1 complete and 35 partial responses. Disease control rate in intensively pre-treated patients with mBC reached 84.16 % (84/101). Adverse events (AE) of any severity were recorded in 25.74 % of cases. The main adverse events with ixabepilone were neutropenia and peripheral polyneuropathy. In no case did toxicity lead to early discontinuation of treatment or death. In patients with mBC progression after anthracyclines and taxanes, the combination of ixabepilone with capecitabine or ixabepilone with trastuzumab demonstrates extremely high disease control rates in modern Real Clinical Practice (RCP). Ixabepilone monotherapy is an option of choice in patients with breast cancer progression after anthracyclines, taxanes and capecitabine.

Objective. Comparative evaluation of the duration of training and immediate results of treatment with videothoracoscopic (VATS) lobectomy via two-port access and open lobectomy in novice surgeons. Material and methods. The study included 118 surgical interventions performed in the thoracic department of AU RKOD of the Ministry of Health of the Chuvash Republic from January 2021 to February 2023. For comparative evaluation of the two learning curves, the operations were divided into two groups: the first group included VATS lobectomies performed via two-port access by a surgeon with initial zero experience in performing such operations (n=50) but with more than 5 years of experience in thoracic oncology; the second group included surgical interventions (n=68) performed by surgeons with less than 5 years of experience in thoracic surgery. Results. Evaluation of the learning curves showed that 31 operations were required to master VATS and 29 for open lobectomies, after which the duration of operations did not change significantly. The duration of surgery was longer in the VATS group (190 (150—230) min vs. 150 (122.5—175) min; p=0.0004). Blood loss was not statistically different in both groups (VATS 100 (50—200) ml, open lobectomy 75 (50—100) ml; p=0.42). The duration of drainage was shorter in the VATS group (6 (4—7) days vs. 7 (6—8) days; p=0.0000). The number of removed lymph nodes was higher in the thoracoscopic lobectomy group (11.5 (8.5—16) vs. 8.5 (7—12.5); p=0.01). Conclusion. The learning curves for VATS lobectomy and thoracotomy lobectomy are comparable. The level of competence and safety for performing standard lobectomies is achieved on average for both techniques after 30 operative procedures. However, significantly more operations are required to achieve mastery and to perform combined lobectomies.