В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

Background: Due to the low efficacy of PD-L1 antibodies in second and subsequent lines of metastatic gastric cancer (mGC), the optimal treatment strategy of such patients and appropriate choice of predictive biomarkers remain challenging. The aim of our study is to assess the efficacy of immune checkpoint inhibitors monotherapy in patients with mGC in routine clinical practice, especially in heavily-pretreated patients. Materials and methods: We retrospectively analyzed data of patients treated in five oncology centers in Moscow between 2018 and 2023, who received nivolumab or pembrolizumab for advanced gastric cancer. Primary end-point of our study was 6-months PFS. Secondary end-points were overall survival (OS), objective respons e rate (ORR), and disease control rate (DCR). Toxicity was assessed using CTC AE v5.0 scale. Results: 122 patients with mGC who received immune checkpoint inhibitors were included between 1 January 2018 and 28 February 2023. 6-months PFS rate was 31,6 %. The median OS was 7 months (95 % CI: 2–20), the median PFS was 3 months (95 % CI: 1,5–9,5). A statistically significant difference in OS was detected in patients with MSI compared to MSS (25 months vs 6 months; 95 % CI: 0,21–0,86; HR: 0,43). A trend towards higher PFS was observed as well (10 months in MSI vs 3 months in MSS; 95 % CI:0,26–1,01; HR: 0,51). No statistical significance in PFS and OS according to PD-L1 CPS was found among patients with MSS. ORR and DCR were 36,6 % and 10,6 %, respectively. No cases of pseudoprogression or fatal immune-related AEs were observed. Conclusion: Our real-world data is consistent with published literature and the results from clinical trials. Further studies are needed to determine prognostic factors and to establish prognostic model of patients receiving ICIs for optimal treatment strategy of mGC.

Given the poor treatment outcomes of disseminated gastric cancer (dGC), the search for new drug treatment options remains a pressing issue. According to some literature, the use of a chemotherapeutic triplet in the first line improves patient survival rates. An interim analysis of a prospective randomised phase III trial examines the comparison of the chemotherapeutic regimens mFOLFIRINOX and mFOLFOX6 in the first-line treatment of HER2-negative gastric adenocarcinoma. In this interim analysis, significant differences between patients receiving mFOLFIRINOX or mFOLFOX6 regarding the primary endpoint of mVBP were detected only in the group of patients with dissemination to the retroperitoneal lymph nodes. Overall, based on the results of this work, it can be concluded that the majority of patients do not require intensification of first-line treatment for gastric adenocarcinoma in the form of mFOLFIRINOX chemotherapy. However, final conclusions on the efficacy of the triple combination can only be drawn upon completion of the entire study.

Introduction: The main current approach to the treatment of patients with resectable cancer of the stomach and gastroesophageal junction (GEJ) is perioperative FLOT chemotherapy. The mFOLFIRINOX regimen has been shown to be effective and safe in disseminated adenocarcinoma of the stomach and GEJ. This article presents preliminary results of the efficacy and safety assessment of perioperative FOLFIRINOX chemotherapy in patients with resectable cancer of the stomach and gastroesophageal junction.Materials and Methods: The FOLFIRINOX / FLOT study is a phase 2 / 3 open-label, randomized trial. Study enrollment was started in January 2019 and is currently ongoing. The inclusion criteria are: histologically confirmed resectable adenocarcinoma of the stomach or gastroesophageal junction, Siewert types II–III, clinical stage cT4aN0M0, cT1–4N1–3M0 or cT2–4N0–3M0, with total or subtotal involvement of the stomach. The following regimens were used for perioperative chemotherapy: FLOT — docetaxel 50 mg / m2 on day 1, oxaliplatin 85 mg / m2 on day 1, leucovorin 200 mg / 2 on day 1, 5FU 2600 mg / m2 × 24 hours starting on day 1, or mFOLFIRINOX — irinotecan 180 mg / m2 on day 1, oxaliplatin 85 mg / 2 on day 1, leucovorin 200 mg / m2 on day 1, 5FU 250 mg / m2 bolus on day 1 and then 2200 mg / m2 × 48 hours on day 1. The primary endpoint was 5‑year overall survival.Results: All planned preoperative courses of chemotherapy had been administered to 25 (86 %) patients in the FLOT group (n = 29) and 22 (92 %) patients in the FOLFIRINOX group (n = 24). Four (12 %) and 2 (8 %) patients in the FLOT and FOLFIRINOX groups, respectively, discontinued the treatment. The surgical staging was used in 48 patients (91 %) (25 [86 %] in the FLOT group and 23 [96 %] in the FOLFIRINOX group). Complete tumor regression (Mandard grade 1) had been achieved in 4 patients (2 [7 %] in the FLOT group and 2 [8 %] in the FOLFIRINOX group). Postoperative complications were detected in 2 patients (8 %) in the FLOT group and 4 (17 %) in the FOLFRIRNOX group. Thirty-three patients (62 %) received all scheduled postoperative treatment courses (n = 19, 66 % for FLOT and n = 14, 58 % for FOLFIRINOX).Conclusions: The preliminary results of the FOLFIRINOX / FLOT study showed comparable tolerability of the regimens and comparable complete pathological response rates. However, there was a higher incidence of postoperative complications detected among patients who received the FOLFIRINOX regimen compared to the FLOT group.

Malignant neoplasms (MNP) of the gastrointestinal tract in children are extremely rare and account for 1.2 % of all MNP. According to world literature, the incidence of gastric cancer is no more than 0.05 % of all cases of MNP of the gastrointestinal tract in children. In national and foreign literature, only isolated cases of stomach cancer in children and adolescents aged 10 to 18 years are described. Clinical manifestations of the disease, as in patients over the age of 18, are non-specific – epigastric pain, loss of appetite, weight loss, ascites, anemia, melena and others. In this regard, the diagnosis occurs at the late stages of the disease and, therefore, is characterized by an unfavorable prognosis. Gastric signet ring cell carcinoma (SRCC) is an uncommon histologic subtype of adenocarcinoma and usually occurs in people aged 20 to 40 years. We would like to report an extremely rare case of SRCC in a 14-year-old child.

The Russian consensus on prevention, diagnostic and treatment of gastric cancer was prepared on the initiative of the Moscow clinical scientific center named after A. S. Loginov according to the Delphi method. Its aim was to clarify and consolidate the opinions of specialists on the most relevant issues of prevention, diagnosis and treatment of gastric cancer. An interdisciplinary approach was provided by the participation of leading gastroenterologists, oncologists and surgeons.

Background . microsatellite instability (MSI) is a prognostic marker of survival in many malignant diseases and show resistance to chemotherapy at early stages of colorectal cancer and show no benefits from chemotherapy at early stages of colorectal cancer. However, the role of MSI in resectable gastric cancer (GC) remains unknown. Aim. To study the results of treatment of resectable gastric cancer with microsatellite instability. Materials and methods . The study included 286 patients with resectable gC who received treatment at the N. N. Blokhin national medical Research Center of Oncology. All patients underwent PCR testing for MSI-H in 5 markers (BAT25, BAT26, NR21, NR24, NR27). Tumor regression grades (TRG) were evaluated according to the mandard tumour regression score, including disease-free survival and overall survival. Results. MSI indicated in 27 cases (9.44 %) out of 286 resectable gastric cancer. In group patients who received only surgical treatment, 2-year disease-free survival in patients with MSI-H was 77.80 % versus 88.29 % in MSS patients (hazard ratio (HR) 1.82, 95 % confidence interval (CI) 0.37–8.82, p = 0.45), 2-year overall survival in patients with MSI-H was 88.90 % versus 95.36 % in MSS patients (HR 2.03, 95 % CI 0.20–19.8, p = 0.54). In patients who received perioperative chemotherapy, 28.57 % (4 / 14) had progression in MSI-H tumor versus 3.61 % (6 / 166) in MSS tumor (p <0.001). In group patients who received treatment combined with chemotherapy, 2-year disease-free survival in patients with MSI-H was 59.60 % versus 67.36 % (HR 1.96, CI 95 % 0.88–4.35, p = 0.09), 2-year overall survival in patients with MSI-H was 67.30 % versus 85.86 % in MSS patients (HR 1.86, 95 % CI 0.64–5.41, p = 0.25) Conclusion. MSI-H is not a favorable prognosis factor in patients with resectable GC who are treated surgically combined with chemotherapy. The prevalence of progression in patients with MSI-H-status is higher than MSS-status with perioperative chemotherapy (FLOT / FOLFIRINOX).

To date, gastric cancer patients still have a poor prognosis. Current endoscopic or surgical treatment modalities are radical only for early gastric cancer (T1). Curability dramatically declines as tumor invasion progresses and lymph node metastasеs appear. In Europe and North America, the 5-year overall survival rate of patients with stage T2–4 cancer is 20 % [1]. Combination therapy for gastric cancer is being extensively studied to improve the treatment outcomes [2–6]. Currently, perioperative chemotherapy with FLOT regimen is the mainstay of resectable gastric cancer treatment in Europe. FLOT4-AIO randomized study has shown that the FLOT regimen was associated with significant increase in the median overall survival (50 versus 35 months), disease-free survival (18 versus 30 months) and R0 resection rate compared to ECF / ECХ regimen.In this work we evaluated the efficacy and toxicity of perioperative FLOT regimen in patients with gastric cancer and gastroesophageal junction cancer type I–III cT4aN0M0, cT1–4N + M0, using a prospective database of patients treated at the N. N. Blokhin Russian Cancer Research Center.

Introduction. Ramucirumab (R) with paclitaxel (PTX) is a global standard for second-line (2L) therapy in advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) get treated with taxanes in the perioperative or 1st line metastatic setting. For those pts the benefit of a combination of R+P is unclear, and many physicians would choose an irinotecan based regimen as 2L. We present data of retrospective analysis from pts with GEA with docetaxel-containing 1st line treated with ramucirumab and paclitaxel (R+PTX) or FOLFIRI (R+FOLFIRI) as 2L in a «real-life» setting.Materials and methods. We identified 46 docetaxel pre-treated pts from RAMSELGA data-base who received R+PTX (n = 19) or R+FOLFIRI (n = 27) as 2L.Results and discussion. The median progression-free survival (MPFS) and median overall survival (MOS) for pts treated with R+PTX were 7.9 (95% ДИ: 6.2–9.7) and 18.1 (15.1–21.2) months, and those for pts treated with R+FOLFIRI – 7.1 (95% ДИ: 4.3–9.9) and 15,8 (12.1–19.5) months, respectively. There are no significant differences. Main adverse events of special interest were hypertension grade (gr) 1-2, epistaxis gr 1-2: 78.9% и 21.1% in R+PTX group and 29.6% и 22.2% in R+FOLFIRI group, there were serious adverse events in R+FOLFIRI: hypertension gr4 (1 pt), gastrointestinal haemorrhage (1pt), gastrointestinal perforation gr 3 (1pt), death of stroke (1 pt) and gastrointestinal haemorrhage (1pt).Conclusion: docetaxel pre-treated pts seemed to derive pronounced benefit from FOLFIRI-Ram, providing a rationale for a phase III trial.

According to the data of the world statistics, gastric cancer (GC) occupies the 5th place by morbidity and the 3rd one by mortality among malignant neoplasms. A significant proportion of patients are elderly patients, the proportion of which in real clinical practice can reach up to 60%. Ramucirumab is among the standards of second-line drug therapy both in monotherapy and in combination with paclitaxel. The feasibility of prescribing ramucirumab to patients with disseminated cancer of the elderly and its satisfactory tolerability is shown in a subgroup analysis of the REGARD and RAINBOW studies. The use of paclitaxel, included in the standard first-line regimens, may be limited by persistent neurotoxicity, a side effect of platinum derivatives. In this regard, the effectiveness of the combination of ramucirumab with the FOLFIRI regimen as a second-line therapy began to be studied. The article presents a clinical case of achieving a partial effect on the second-line therapy with ramucirumab with FOLFIRI regimen in a 74-year-old patient with HER2-negative gastric adenocarcinoma while registering rapid progression after 4 courses of first-line chemotherapy in XELOX regimen. Tolerability of the second line was acceptable: asthenia grade 1, stomatitis grade 1-2, neutropenia grade 3 were observed, so the irinotecan dose was reduced to 165 mg/m2. By June 2021, there were 10 28-day cycles of treatment, which is ongoing. The duration of disease control in the second line therapy was 11+ months, of which 9+ months – on the background of FOLFIRI regimen drug therapy with ramucirumab.

Gastric cancer (GC) is one of the most common malignant tumours both in Russia and in the world. The drug therapy with consistent use of several therapy lines is the main method for treatment. The number of chemotherapy drugs, which are effective for the treatment of this type of malignant tumours, is limited; the range of targeted drugs is also narrow and includes trastuzumab in the first-line regimen for the treatment of HER2-positive gastric cancer and ramucirumab in the second-line regimen. Immune checkpoint inhibitors made a revolution in the treatment of many cancers. The efficacy of nivolumab, T cell inhibitory receptor of PD-L1, has been proven in the third-line regimen in disseminated gastric cancer. The ATTRACTION-2 randomized study showed that nivolumab significantly increased the median overall survival (from 4.14 to 5.26 months, p < 0.0001), progression-free survival (from 1.45 to 1.61 months, p < 0.0001); objective response with a median duration of 9.5 months was achieved in 11.2% of patients, stable disease in 29.1%. The median time to progression was 1.61 months. The toxicity of the treatment was quite low and led to discontinuation of treatment in only 1% (n = 4) of patients, who had previously received massive chemotherapy. Only patients from Asia took part in the ATTRACTION-2 study. However, its results were confirmed in the CheckMate-032 study in the non-Asian patient population: the objective response rate was 12%, the median DOR was 7.1 months, the median progressionfree survival was 1.4 months, and the median overall survival was 6.1 months. Nivolumab was effective for the treatment of MSI-H and MSS, PD-L1-positive and PD-L1-negative tumours. Nivolumab is a recognized and well-tolerated standard of late-line therapy in disseminated gastric cancer. The range of indications for its prescription will be expanded in the nearest future.

Aim. The main objective of the prospective multicentre observational study is to describe adverse events occurred during treatment with aflibercept plus FOLFIRI therapy in real life practice. In despite of broad use of aflibercept in Federal oncological centers, this regimen is still perceived by healthcare professionals (HCPs) as having worse safety profile in comparison with other antiangiogenic agents. Taking into account limited experience of using aflibercept in Russia it s critically important to evaluate and document adverse events occurred with treatment in aflibercept plus FOLFIRI regimen in patients with metastatic colorectal cancer (mCRC) in real-life practice. Methods. The physician selection was performed as a random process. Twenty sites with experience in treatment of mCRC patients were selected. The investigators were encouraged to enroll all patients meeting eligibility criteria in consecutive manner. Total number of included patients into the study patient was 101. Data were evaluable for 91 patients. 14 of 91 (15.4 %) patients didn ’t meet inclusion criteria and were excluded from the per protocol analysis: 10 patients didn ’t receive oxaliplatin within the last line of therapy preceding inclusion into the study and in 4 patients progression occurred more than 6 months after the end of adjuvant therapy. Results. Overall, 265 treatment emergent adverse events (TEAEs) occurred in the 77 patients analysed per protocol. In total, 23 grade 3 and 5 grade 4 TEAEs were reported by 16 and 4 patients, respectively. The most common TEAEs were nausea (68 events in 31 [40.3 %j patients), diarrhea (43 events in 25 [32.5 %j patients), hypertension (36 in 20 [26.0 %] patients), neutropenia (29 events in J5 [J9.5 %] patients), asthenia (28 events in 12 [15.6 %]patients). Three cases of grade 1-2 stomatitis were reported in 2 (2.6 %) patients. And one patient reported grade 1 epistaxis during the study. There was no case of gastrointestinal perforation, fistula development, ulceration, arterial or venous thromboembolism. During this study seven serious adverse events were documented in 5 (6.5 %) patients of 77. The reason for treatment discontinuation in 5 (11.1 %) of 45 cases was adverse event. No death, classified as related to any component of therapy, was reported in this study. Conclusion. This national (Russian) prospective multicentre non-interventional study conducted in patients with mCRC in daily practice suggests that aflibercept plus FOLFIRI has a manageable safety profile in line with VELOUR phase III study.

Background. Ramucirumab is a monoclonal antibody that inhibits the vascular endothelial growth factor receptor-2 (VEGFR2). The study is aimed to analyse prognostic factors for survival in patients with disseminated gastric cancer who received ramucirumab in the second-line therapy in ’real-life’ clinical setting of Russia (RAMSELGA). Methods. We retrospectively analysed the outcome of 163 patients aged 20–78 years from 11 oncological centres in Russia. Survival analysis was performed using the Kaplan – Meier model, and regression analysis was performed using the Cox model. Results. In a univariate analysis of overall survival, 5 factors were identified as independent factors of an unfavourable prognosis: 1) age <65 years (RR 0.542; 95% CI 0.302–0.971; p = 0.039); 2) time to tumour progression on the first-line therapy is not more than four months. (RR 0.161; 95% CI 0.105–0.246; p = 0.0000); 3) a low grade tumour or colloid cancer (RR 1,868; 95% CI 1,063–3,284; p = 0,030); 4) peritoneal metastasis (RR 1.549; 95% CI 1.026–2.339; p = 0.037); 5) ascites or pleurisy (RR 0.624; 95% CI 0.424–0.920; p = 0.017). In a multivariate analysis, favourable prognostic factors of overall survival of patients included age – 65 years or older (OS 2.288; 95% CI 1.240–4.220; p = 0.008) and time to tumour progression on the first-line therapy – more than 4 months (OS 6.650; 95% CI 4.221–10.477; p = 0.000). Conclusion. Despite an active search, prognostic factors for survival in patients that are universal for dGC have not yet been found. To build a universal prognostic model, a very thoughtful analysis considering not only clinical and laboratory, but also pathomorphological and molecular genetic characteristics is required.