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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.

Tyrosine kinase inhibitors of the first, second and third generations are the main treatment method for non-small cell lung cancer with EGFR mutation. About 60% of patients progressing on a first-generation or second-generation tyrosine kinase inhibitor acquire T790M mutation. An alternative is first-line osimertinib, but second-line treatment options are limited, and therefore it is important to find a strategy that allows to extend the effective treatment of TKI. One of the rational approaches is the use of a combination of a first-generation tyrosine kinase inhibitor with anti-VEGF agents. The available information sources show an increase in the effectiveness of the combined use of erlotinib and antiangiogenic drugs-bevacizumab and ramucirumab. The combination of erlotinib and bevacizumab in several studies of the second — third phase, led to a statistically significant increase in progression-free survival, but did not show a significant increase in overall survival. In the Phase 3 RELAY study, the combination of erlotinib and ramucirumab showed comparable efficacy with the third-generation TKI — osimertinib in the first line, however, overall survival results are not yet available. At the same time, there are more opportunities to choose the secondline mode, taking into account the known frequency of detection of the T790M mutation. The optimal treatment sequence is discussed, with the option of prescribing a combination of erlotinib with bevacizumab or ramucirumab in the first line and osimertinib in the second in the presence of the T790M mutation. In such patients, osimertinib may be prescribed in the second line.

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.

Ramucirumab is a human anti-vascular endothelial growth factor receptor 2(VEGFR-2)monoclonal antibodythat acts on vascular endothelial cells to inhibit angiogenesis. Ramucirumab in monotherapy or in combination with paclitaxel or FOLFIRI has proven to prolong overall survival in patients with pretreated metastatic gastric/gastrooesophageal junction adenocarcinoma. In clinical practice combination with ramucirumab showed promising efficacy with median overall survival in 9,6 months and manageable toxicities. Most common specific adverse events in ramucirumab were impaired wound healing, hypertension, bleeding and perforation. In several article describe dysphonia induced by anti-angiogenic compounds.Herein, we report on a case a high activity ramucirumab in combination with FOLFIRI. This report aims to present a long-term survivor of recurrent gastric cancer and describe dysphonia induced by ramucirumab.

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

Introduction: Ramucirumab (Ram), a human IgG 1 antibody against vascular endothelial growth factor receptor 2. This multicenter retrospective study aims to reviewed the results of Ram-based therapy as second-line treatment in patients with advanced gastric cancer in a real-life setting.Methods: it was an observational, retrospective study carried out in 11 Russian hospitals. Endpoints included safety, overall survival (OS), progression-free survival (PFS), objective response rate (ORR).Results: 163 patients were included. Ram was used as the second- line in 166 combined with weekly paclitaxel (PTX) in 104 patients or irinotecan-based chemotherapy (mostly FOLFIRI) in 42 patients and as monotherapy in 17 patient. In second line VEGF-related toxicity (all grades) included epistaxis (39,2%), proteinuria >1g/day (4.9%), and arterial hypertension (68%); grade 3-4 toxicity was bleeding (4.3%), perforation (2,4%), venous thrombosis (6,13%) and brain ischemia (0.6%, grade 5). 15 patients (9,2%) discontinued therapy due to toxicity.Conclusion: These real-life efficacy data of ramucirumab are in line with previous randomized trials. Ramucirumab is well tolerated in daily clinical practice.

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with unmet needs of effective medications. Lenvatinib – a new oral multikinase inhibitor (MKI) proved to be as effective as sorafenib in terms of survival has been added recently to standard first-line treatment of advanced HCC. Regorafenib, another MKI in the RESORCE trial, a phase 3 study evaluating regorafenib in HCC patients who experience disease progression after first-line treatment with sorafenib, have shown a 2.8-month median survival benefit over placebo (10.6 versus 7.8 months). Cabozantinib and ramucirumab have all been shown to extend overall patient survival in sorafenib-refractory HCC patients and appear to have a reasonable safety profile. Immune checkpoint inhibitors therapy with nivolumab or pembrolizumab – monoclonal antibody to PD1-receptor are effective in about 15–18% of HСС patients presenting with long-lasting objective responses. Immunotherapy was safe in terms of viral hepatitis activation, but in comparative trials in first and second-line settings failed to achieve statistical difference in overall survival other sorafenib and placebo, respectively. Due to less toxic profile HCC immunotherapy seems to be a reasonable option to Child-Pugh B patients. Multiple ongoing trials are studying immune checkpoint inhibition alone or in combination with TKIs. The results of these trials will help determine the optimal choice, timing, and sequence of agents. This article reviews current situation in the field of new therapies of HCC from the point of common medical practice in searching for optimal second-line treatment decision in different clinical situations.

The low efficacy of cytostatic therapy in mGC led to an active study of the role of molecular targets in the carcinogenesis of GC. Ramucirumab is the only neoangiogenesis inhibitor, which demonstrated its antitumor activity both as monotherapy and in combination with paclitaxel in patients with mGC. A clinical case demonstrated an example of a long-term (26+ months) response to paclitaxel therapy after it was combined with ramucirumab with an acceptable toxicity profile, which allowed a patient to participate in social activities and maintain quality of life.

Background: Several studies show that the combination chemotherapy with ramucirumab allows to improve the treatment results of advanced gastric cancer (GC). Irinotecan with fluoropyrimidines is own of the second line chemotherapy options for these patients. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of irinotecan and fluoropyrimidines with ramucirumab in metastatic GC.Methods: Eligible patients had advanced morphologically verified GC and disease progression during or within 4 months following first-line therapy. They received FOLFIRI plus ramucirumab (8 mg/kg on day 1) or XELIRI in combination with ramucirumab (8 mg/kg on days 1 and 8). The primary end point was progression-free survival (PFS). Secondary end-points were disease control rate (DCR) and safety.Results: Between September 2015 and April 2019, 39 patients (pts) were enrolled and 38 were evaluated for efficacy and toxicity. Median number of cycles was 9 (2-20). Seven patients achieved a partial response (PR) for an overall response rate of 17.9%. A total of 29 (74.4%) patients had stable disease (SD) for a DCR of 92.3%. With a median follow up 7,5 months, median PFS was 7.58 months (95% CI 6.6-8.5) and the median OS has not yet been reached. Median duration of PR response was 8,7 months (4,11-10,94+) and median duration of SD was 4,14 months (1,84-11,99+). The main treatment-related grade 3 or 4 adverse events were neutropenia (7/38; 18.4%), anemia (1/38; 2.6%) and diarrhea (2/38; 4.3%).The most frequent adverse events of special interest (AESIs) any grade were hypertension (16/38; 42.1%), bleeding/hemorrhage (10/38; 26.3%), proteinuria (6/38; 15.7%) and venous thromboembolic events (10/38; 26,3%). Gastrointestinal perforation developed in two patients (2/38; 5.3%). No treatment-related deaths occurred.Conclusion: In our research ramucirumab with irinotecan and fluoropyrimidines demonstrate the high activity and a manageable safety profile in patients with pre-treated metastatic GC

Background. Working out of the second line chemotherapy of advanced gastric adenocarcinoma is a promising approach to cancer therapy. Ramucirumab, an anti-angiogenic agent specifically targeting vascular endothelial growth factor receptor-2 (VEGFR-2). In April 2014, the FDA approved ramucirumab as a single agent or in combination with paclitaxel for treatment of advanced gastric or gastroesophageal junction adenocarcinoma that has progressed on or after prior fluoropyrimidineor platinum containing chemotherapy based on data of REGARD and RAINBOW trials.Materials and Methods: From June 2016 to 15Jan 201837 pts with advanced GC were treated with ramucirumabin the second line treatment as single agent (11 pts) or in combination with paclitaxel (26 pts) in N.N.Blokhin National medical research center of oncology.Results: edian PFS (MPFS) and median OS (MOS) was 1,8 and 7,6 mons for monotherapy group. For combination group MPFS was 4,0mons, MOS -10,6 mons. Ramucirumab had an acceptable safety profileConclusions:ur data are similar to the data of international randomized trials.

Ramucirumab is a monoclonal antibody targeting vascular endothelial growth factor receptor 2. In two randomised clinical trials Ramucirumab either alone or in combination with paclitaxel has been found to be safe and effective for patients with previously treated advanced gastric cancer. One of the serious adverse events associated with ramucirumab is bleeding.We report the case of a 56-year-old man with advanced gastric cancer located at the gastroesophageal junction with liver, pulmonary and multiple lymph node metastases, plevritis was treated with a paclitaxel plus Ramucirumab regimen. We demonstrate a case of a cardioesophageal junction bleeding due to the high efficiency of treatment. He was successfully treated with by applying only hemostatical therapy, but after stop the bleeding chemotherapy was not reintroduced. The partial response was maintained for approximately 10 months. The patient died on 28 November 2017.Chemotherapy with best supportive care for metastatic gastric cancer shown the improvement the performance status, help keep the cancer under control and help relieve symptoms during the time.

Background. Gastric cancer is the fifth most common malignancy worldwide with diagnosis often occurring at an advanced stage. For the majority of advanced gastric cancer patients, chemotherapy typically is used as first-line treatment, although many patients will also require second-line treatment. Ramucirumab (Cyramza®, Eli Lilly and Company, Indianapolis, Indiana, USA) recently has received worldwide and United States Food and Drug Administration approval for gastric cancer in the second-line setting. Case reports. A series of five advanced gastric cancer cases is presented, outlining each patient’s diagnosis and treatment. All patients were treated with intravenous ramucirumab (8 mg/kg on days 1 and 15) plus paclitaxel (80 or 100 mg/m2 on days 1, 8, and 15 of a 28-day cycle) after disease progression on or after first-line chemotherapy. Patient outcomes are described including an outline of treatment-related adverse events and quality of life. All patients were able to achieve a clinical response and stable disease. Conclusion. Our case series demonstrates that ramucirumab, in conjunction with paclitaxel, is an effective and well-tolerated treatment option for advanced gastric cancer patients who have disease progression following first-line chemotherapy.

Angiogenesis has become an important target in the treatment of solid tumors and anti-angiogenic agents are a promising approach to cancer therapy. Ramucirumab, an anti-angiogenic agent specifically targeting vascular endothelial growth factor receptor-2 (VEGFR-2). In April 2014, the FDA approved ramucirumab as a single agent or in combination with paclitaxel for treatment of advanced gastric or gastroesophageal junction adenocarcinoma (GC) that has progressed on or after prior fluoropyrimidine – or platinumcontaining chemotherapy based on data of REGARD and RAINBOW trials.We evaluated the progression free (PFS), overall survival (OS) and safety of ramucirumab in patients (pts) with advanced GC in routine clinical practice From June 2016 to 20 Sep 2017 40 pts with advanced GC were treated with ramucirumab in the second line treatment as single agent (8 pts) or in combination with paclitaxel (26 pts) in N.N.Blokhin National medical research center of oncology.Median PFS (MPFS) and median OS (MOS) was 1,8 and 7,6 mons for monotherapy group. For combination group MPFS was 5,02 mons, MOS was not reached. Ramucirumab had an acceptable safety profile Our data are similar to the data of REGARD and RAINBOW trials.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. The prognosis of advanced gastric cancer remains poor despite therapeutic advances in recent decades. Several recent positive phase III trials established the efficacy of second-line chemotherapy for metastatic gastric cancer in prolonging overall survival. Many targeted-therapies failed to show a significant survival benefit in GC, only 2 of them are approved FDA: trastuzumab in the 1-st line treatment of HER2-positive gastric cancer and ramucirumab with or without paclitaxel as second line chemotherapy. The article presents the case of effective treatment of patient with Her2-negative advanced gastric cancer. A 76-year-old man had a moderately differentiated adenocarcinoma of gastric with synchronous multiple liver metastases. He received ramucirumab with paclitaxel as second -line chemotherapy. The size of the liver metastases was reduced and he maintained a partial response for one year. This clinical case report demonstrates that new option in the treatment of advanced gastric cancer can to allow our patients to live longer without losing the quality of life.