Aim . To assess the efficacy and safety of lenvatinib and pembrolizumab for the treatment of mismatch repair-proficient endometrial cancer (EC) in routine clinical practice in Russia. Materials and methods . This multicenter, retrospective, cohort study included patients with recurrent and metastatic EC from 37 cancer centers in Russia treated between May 2020 and April 2023. Patients with histologically verified EC without microsatellite instability who received ≥1 course of pembrolizumab/lenvatinib therapy were included in the study. The primary endpoint was progression-free survival; the clinical characteristics of the patients were additionally analyzed, the objective response rate and the toxicity profile of therapy were assessed. Results . The study included 100 patients. Median age was 65 (30–83) years. The most common histologic tumor subtype was endometrioid adenocarcinoma (68 %); serous adenocarcinoma was diagnosed in 22 % of cases, other types of tumor – 10 % of cases. All patients had pMMR/microsatellite-stable tumors. The median progression-free survival was 7.75 months (95 % confidence interval 0.7–33.8), and a partial response to therapy was observed in 24 % of patients. Almost half of the patients (44 %) required dose reduction due to adverse events. The most common adverse events included fatigue (n = 26; 26 %), hypertension (n = 20; 20 %), and hypothyroidism (n = 14; 14 %). Conclusion . This study confirms the clinical efficacy of lenvatinib and pembrolizumab in patients with recurrent and metastatic EC without mismatch repair system deficiency (pMMR-tumors) in routine clinical practice.

Background. Endometrial cancer (EC) treatment outcomes need to be improved. Immunotargeted therapy lead to long-term and delayed effects compared to chemotherapy. Estimation of long-term efficacy and quality of life are crucial when we are talking about efficacy in whole.Aim. To evaluate the long-term clinical efficacy of lenvatinib plus pembrolizumab therapy in patients with EC.Materials and methods. The study included 43 patients with stages I-IV EC with mismatch repair-proficient tumors and treatment duration of more than 9 months. We evaluated median progression-free survival, objective response, duration of treatment depending on the line of therapy, prevalence and type of adverse events, and correction regimens. Results. Lenvatinib plus pembrolizumab treatment was safe and efficacious in recurrent EC. Median of progression-free survival (patients with response or stabilization more than 9 months) is 10.2 months (95 % confidence interval 9.1-13.0), median of follow up is 9.7 (1.4-33.8) months. There were no complete responses, partial response was in 12 (28 %) patients, disease stabilization was in 31 (72 %) patients. Regarding safety, the overall rate of any-grade adverse events was 56.3 %. The most common treatment-related adverse events were fatigue (32.6 %), hypertension (23.3 %), and hypothyroidism (18.6 %). Dose reduction was performed in 22 (51.2 %) patients.Conclusion. The combination of lenvatinib plus pembrolizumab has long-term efficacy and manageable profile of safety. The presence of a significant pool of patients with durable response allows improving the survival rate of such patients in Russia.

Introduction. In the structure of Russian cancer incidence, malignant neoplasms (MN) of the liver occupy 1.61%. Patients with initially unresectable hepatocellular cancer (HCC) or progressive HCC after local treatment methods, in the absence of contraindications, are subject to systemic therapy.Aim. To evaluate the direct effectiveness and long-term results of treatment of patients with inoperable HCC with the combination of atezolizumab and bevacizumab in real clinical practice.Materials and methods. A multicenter (7 centers) retrospective observational study was conducted. It includes 56 previously untreated patients and 12 pretreated patients with a confirmed diagnosis of HCC who were treated with atezolizumab and bevacizumab. The male to female ratio was 2:1, with an average age of 60 years. ECOG 0-1 was in 86.8%, Child-Pugh liver function A – in 76.5%, B – in 23.5%, macroscopic portal vein invasion – in 27.9%, extrahepatic spread – in 35.3%, AFP more than 400 IU/ml – in 38.2%.Results. Use of the atezolizumab and bevacizumab regimen as a first line led to a partial response in 7 patients (12.5%), to stabilization in 39 (69.6%), to progression in 10 (17.9%). The disease control rate was 82.1%, median progression free survival (PFS) was 9.9 months (95% confidence interval (CI) 6.2-n/a). Median overall survival (OS) was not reached (95% CI 10.2-n/a). PFS was significantly influenced by the functional state of the liver according to the Child-Pugh scale. Median PFS in class A was 18.0 months, in class B – 5.6 months: HR 2.54; 95% CI 0.92–7.05; p = 0.03.Conclusion. The atezolizumab and bevacizumab regimen in real clinical practice demonstrates tolerability of therapy and treatment results that are not inferior to the data obtained in the registration study. No new adverse events were identified.

Introduction. The addition of durvalumab after chemoradiation therapy in unresectable stage III non-small-cell lung cancer (NSLC) is a new standard of care.Aim. Study the features and outcomes of durvalumab maintenance treatment after chemoradiotherapy in patients with unresectable stage III NSCLC in the real-world clinical practice in Russia.Materials and methods. 50 patients with unresectable III stage NSCLC after concurrent or sequential chemoradiotherapy (CRT) were enrolled in this observational retrospective study. Median follow up time at primary analysis was 12.4 months.Results. A mean age of the patients in the study was 61.2 years (58.4-64.1; 95% CI). Most of the patients had received sequential CRT (76%, n = 38). Median time of durvalumab start from the end of CRT varied from 22 to 50 days (overall - 35 days). Estimated median PFS and OS were 10.86 months (7.78-14.01, 95% CI) and 26 months (20.19-31.81, 95% CI), respectively. There was a trend toward increased PFS in patients with smoking history: 12 months (9.79-14.2; 95% CI) versus 4,9 months (0.0-12.47; 95% CI), p = 0.2. Half of the patients without smoking history (5/10) had targetable mutations (EGFR ex 19, ALK, ROS1, cMET). Most common reported adverse events of special interest were pneumonitis grade 1-2 (36%, n = 18), leading permanent treatment discontinuation to in 6% of patients (n = 3). There were no reported cases of grade 3-4 adverse events.Conclusions. Real-world characteristic of patients in our study were different from PACIFIC trial. Sequential CRT is the most frequent treatment option in locally advanced unresectable NSCLC in Russia. Estimated PFS was shorter than in PACIFIC, but there were less cases of pneumonitis.

e20553 Background: PD-(L)1 inhibitors are approved immunotherapy agents in treatment for mNSCLC, however, limited data exists about switching between different anti-PD1 antibodies. Our study aimed to evaluate the safety and efficacy of the interchangeability of nivolumab, pembrolizumab, and atezolizumab in patients (pts) with mNSCLC in the 2nd and 3rd line. Methods: We retrospectively evaluated data of pts with mNSCLC treated in four oncology centers in Moscow and SaintPetersburg (Russia). Inclusion criteria were as follows: histologically confirmed mNSCLC with no driver mutations, performance status ECOG 0-2, monotherapy of anti-PD(L)1 antibody, and switching to another PD(L)1 inhibitor for any reason except progression disease or toxicity after initiating of immunotherapy. The primary end-point was progression-free survival (PFS), and secondary end-points were the rate of all grades and grade 3-4 adverse events (CTC AE 5.0). A sample size of 83 achieves 80% power to detect an equivalence difference of 15% in 3-months PFS after the change of anti-PD1 antibody with a one-sided significance level of 0,05. Results: A total of 103 patients (27% female) were included with a mean age of 66 years (33-93). 0-1, 2, and ≥3 organs with metastases have 70 (68%), 17 (17%), and 16 (16%) pts, respectively. Performance status ECOG 0, 1, and 2 was in 16 (16%), 70 (68%), and 17 (17%) pts, respectively. 50 (48%) patients received pembrolizumab, 40 (39%) pts received nivolumab, and 13 (13%) pts – atezolizumab. 48 (47%) pts were switched to atezolizumab, 28 (27%) pts were switched to nivolumab, 26 (25%) pts – to pembrolizumab. The median duration of treatment with the first anti-PD(L)1 antibody was 6 months (1-53 months), with the second PD(L)1-inhibitor was 3 months (1-41 months). Within 3 months after 1 replacement of the drug, there were 77 (74,7%) pts without progression. With the median follow-up of 8 months (1-41), the estimated 3-month PFS was 79,3%. The efficacy of switching was not associated with the agent (HR 0,97, 95CI 0,68-1,38, p = 0,9). There were 2 cases of AEs of 3-4 grades when switching to the second drug. Conclusions: Switching from one anti-PD(L)1 antibody to another in pts with mNSCLC is possible in case of limited access to PD(L)1 inhibitors.

Objective: to re-evaluate the efficacy and safety of lenvatinib with pembrolizumab in unselected Russian renal cell carcinoma (RCC) patients, included in the phase IV study, in a median follow-up extended to 17.1 months. The primary end point was progression-free survival (PFS), secondary end points were overall survival (OS), objective response rate (ORR) and duration of response (DOR), disease control rate (DCR) and its duration, as well as safety. Materials and methods. The study included medical data of 165 patients with verified advanced RCC who received lenvatinib with pembrolizumab in 36 centers of the Russian Federation from 05.02.2018 to 25.07.2024. The median age was 60 (20-76) years, the male to female ratio was 2.3:1. The majority of patients had Karnofsky performance status >= 80 % (74.6 %), clear cell RCC (93.3 %) without sarcomatoid differentiation (93.3 %), metachronous metastases (50.9 %) localized in >1 organ (75.2 %), were nephrectomized (63.0 %) and did not receive antitumor therapy (91.0 %). At the time of lenvatinib with pembrolizumab therapy start 40 patients (24.2 %) were classified into International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable prognostic group, 92 (55.8 %) in the intermediate prognostic group, and 33 (20.0 %) in the poor prognostic group. The median follow-up was 17.1 (1.5-72.9) months. Results. The median PFS achieved 24.0 (18.7-29.3) months, 17-month PFS- 60.5%. The median OS was 48.9 (18.5- 79.2) months, 17-month OS - 76.1 %. Objective response was registered in 46.0 % of patients including 2.4 % complete responders; the DCR was 92.1 %. The median DOR was 16.6 (2.1-72.9) months, duration of disease control - 14.3 (2.1-72.9) months. Confirmed dynamics of change in the sum of tumor foci diameters was recorded in 152 patients, while the median change was -25 % (from -100 % to +29 %). Any decrease in the sum of tumor foci diameters occurred in 69.1 % of cases. The incidence of any adverse events (AE) was 78.2 %, severe AE - 24.2 %, and serious AE - 9.7 %. Immune-mediated AEs developed in 17.0 % of cases and AE grades 3-4 in 6.7 % of cases. Mortality from AEs was 1.2 %. Conclusion. Compared with the registration study, in real-world clinical practice in patients with advanced RCC the lenvatinib with pembrolizumab provides a lower ORR with comparable PFS and OS rates and demonstrates a satisfactory safety profile.

Objective: to compare the efficacy and toxicity of aflibercept and bevacizumab in combination with fOLfIRI in secondline therapy for patients with metastatic colon cancer.Materials and methods. we performed a retrospective analysis of data on patients with metastatic colon cancer treated in 9 clinics in the Russian federation. The inclusion criteria were as follows: metastatic or locally advanced colon cancer; treatment with bevacizumab or aflibercept plus fOLfIRI in the second-line therapy. The primary outcome measure was progression-free survival (PfS). Secondary outcome measures included objective response rate and incidence of adverse events.Results. A total of 271 patients with metastatic colon cancer who received second-line therapy with bevacizumab (n = 81) or aflibercept (n = 190) between 2014 and 2018 were selected for this study. Study groups were matched for main prognostic signs. The objective response rate was 18.1 % in the bevacizumab group and 20.5 % in the aflibercept group (p = 0.7). The median PfS was 5 months (95 % confidence interval 3.8–6.1) in the aflibercept group and 7 months (95 % confidence interval 0.81–2.1) in the bevacizumab group (hazard ratio 1.4; 95 % confidence interval 0.99–2.1; p = 0.04). multivariate regression analysis demonstrated that the type of the targeted drug independently had no effect on PfS (hazard ratio 1.3; 95 % confidence interval 0.9–1.9; p = 0.2). we observed no statistically significant differences in the incidence of complications of any grades between the groups (58 % vs 72 %, p = 0.1). Patients receiving aflibercept were more likely to develop grade III–Iv arterial hypertension (2 % vs 9.5 %) and diarrhea (0 % vs 5.4 %), whereas thrombotic complications were more common in the bevacizumab group (10 % vs 1.8 %).Conclusion. we observed no significant differences in objective response rate and PfS between patients with metastatic colon cancer receiving bevacizumab or aflibercept in combination with fOLfIRI as second-line therapy. The toxicity profiles were different. Our findings can be used for choosing an optimal targeted drug for second-line treatment.

Today cancer is considered as a genetic disease without taking into account some metabolic features of the cells due to these molecular abnormalities. At the same time, accumulated scientific data indicate that energy homeostasis of the malignant cells and their microenvironment plays one of the leading roles in the pathogenesis of the neoplasms and the potential treatment sensitivity. Multiple heterogeneity and plasticity of the metabolic signals, as well as their similarity to the energy pathways in normal cells notes the need to find an optimal model for their further research and implementation of the metabolic therapy into clinical practice

Despite the rapid development of new innovative strategies in cancer treatment like immunotherapy, chemotherapy still remains a common choice in many cases. Standard protocols of chemotherapeutic administration rely on a maximal tolerated dose paradigm, however there is growing evidence that this approach is not always optimal. Alternative scheduling, like metronomic - low dose continuous drug administration - were recently proved their efficacy. The space of available variants of drug administration protocols is prohibitively large to be explored empirically, and there is an urgent need of predictive mathematical models for rational chemotherapeutic scheduling design. In this work we tested the ability of the minimal pharmacokinetic-pharmacodynamics model to describe schedule-specific tumor volume time evolution in different mouse tumor models.

Gastric cancer is an aggressive malignant neoplasm of the digestive system. These tumors are genetically heterogeneous,and they could be subdivided into four groups. One of such groups, microsatellite instable (MSI) gastric cancer, is of interest considering prognosis and response to therapy. Immune checkpoint inhibitors present a perspective strategy in treating these tumors, however, there is currently insufficient data on their use in microsatellite instable gastric cancer. Aim of this study was to evaluate objective response to neoadjuvant checkpoint inhibitors treatment in patients with MSI gastric cancer. Eleven patients were enrolled. They received Nivolumab or Pembrolizumab (investigator choice) in a neoadjuvant setting. Objective response was registered in 9 (81,8%) patients, two patients had stabilization. Nine patients (81,8%) underwent radical surgery. Pathologic complete response (pCR) was registered in 3 (33,3%). Postoperative complications were tracked and registered in accordance with Clavien-Dindo classification: grade 1 – 2 patients, grade 2 – 2 patients, grade 3 – 1 patient.

Objective: to compare the efficacy and tolerability of second‑line chemotherapy with original bevacizumab (Avastin) and biosimilar bevacizumab produced by “Biocad” (Avegra) in patients with metastatic colon cancer.Materials and methods. This retrospective observational study included patients with metastatic colon cancer treated in 9 clinics in the Russian Federation. Inclusion criteria were as follows: metastatic or locally advanced colon cancer and second‑line therapy with bevacizumab (Avastin or Avegra). The primary outcome measure was overall survival (OS). Secondary outcome measures included progression‑free survival (PFS), disease control rate (DCR), and incidence of adverse events associated with antiangiogenic therapy.Results. We identified 209 patients with metastatic colon cancer who received second‑line therapy with biosimilar bevacizumab (n = 37; 17.7 %) or original bevacizumab (n = 90; 43 %) or no targeted therapy (n = 82; 39.3 %) between 2014 and 2018. Patients in these three groups were matched for their main prognostic characteristics. The DCR was 59.5 % in the group of biosimilar bevacizumab, 58.9 % in the group of original bevacizumab, and 50 % in the control group (without targeted therapy). PFS was 6 months in the chemotherapy group and 8 months in the groups of bevacizumab (hazard ratio (HR) 0.77; 95 % confidence interval (CI) 0.65–0.91; p = 0.002); the difference in PFS between patients receiving biosimilar bevacizumab and original bevacizumab was insignificant (HR 1.3; 95 % CI 0.81–2.1; р = 0.3). Median OS was 16 months in the chemotherapy group, 30 months in the biosimilar bevacizumab group, and 20 months in the original bevacizumab group (HR 0.89; 95 % CI 0.72–1.1; р = 0.3). We observed a tendency to longer OS in patients receiving biosimilar bevacizumab (HR 0.44; 95 % CI 0.17–1.1; р = 0.08). Bevacizumab‑ associated toxicity was limited to arterial hypertension and was registered in 4 patients with only one patient who developed grade III hypertension.Conclusions. There was no significant difference in PFS between patients receiving biosimilar and original drug, while OS was higher in the group of biosimilar bevacizumab. Both medicines demonstrated similar toxicity. Therapy with biosimilar bevacizumab ensured lower incidence of hypertension and proteinuria compared to the original drug. An additional prospective observational study assessing the efficacy and tolerability of biosimilar bevacizumab in colon cancer patients is needed.

The evolution of drug therapy in solid tumors primarily leads to the increase in cancer specific survival, but inevitably raises financial burden. So far, none of the countries can venture total reimbursement with all necessary contemporary drugs for all patients. Doubling of expenses for cancer drug therapy in Russia in 2019 allowed oncologists using the most expensive treatments in more than 70 % of patients.Purpose: To evaluate efficacy of various treatment types of non‑small cell lung cancer in real clinical setting.Material and methods. We included patients with histologically verified metastatic non‑small cell lung cancer without activating mutations treated with first or second line therapy in 2018 – 2019. In total 287 patients were included: 230 — for the first line efficacy analysis, 100 — for the second. Time to disease progression, overall survival and objective response rate were evaluated.Results. The use of checkpoint inhibitors in accordance with all actual recommendations (first line pembrolizumab monotherapy in PD-L1 > 50 %, chemoimmunotherapy in first line or monotherapy in the second line irrespectively to PD-L1 status) decreased one‑year mortality from 61 % in 2018 to 33 % in 2019, but significantly increased financial cost (p < 0.000). Moreover, checkpoint inhibitors in combination with chemotherapy irrespectively of PD-L1 expression increased response rate (from 10 % and 21 % for monotherapy and platinum doublet, respectively, to 33,2 % for chemoimmunotherapy). PD‑1 inhibitors as monotherapy increased median time to disease progression (4,1 and 6,2 months for monotherapy with chemotherapy and platinum doublet, respectively, to 6,5 months and not achieved for chemoimmunotherapy and monotherapy with checkpoint inhibitors).Conclusion. More than doubling of financial costs spent for non‑small cell lung cancer treatment allowed access to contemporary treatment for all patients. Such unprecedented measures significantly improved efficacy, including double decrease of one‑year mortality. Nevertheless, rational design of regional clinical guidelines interpretation is of great importance in accurate and effective use of the healthcare budget.

Introduction. Trifluridine/Tipiracil (FTD/TPI) is a new chemotherapeutic drug approved in more than 60 countries for use in patients with metastatic colorectal cancer who have registered progression or intolerance to treatment with fluoropyrimidines, oxaliplatin and irinotecan, anti-VEGRand anti-EGFR-targeted agents. This study evaluated for the first time the effectiveness and tolerability of FTD/TPI therapy in the Russian patient population.Materials and methods. A confirmatory open-label single-arm non-randomized trial was conducted in 2 clinical centres in Russia. The main criteria for inclusion were: conduction of at least the 2nd line of standard systemic therapy for metastatic colon adenocarcinoma. The primary efficacy criteria were: 2-month progression-free survival; secondary – median progressionfree survival, disease control frequency, safety assessment, overall survival. Research number: NCT03274882.Results. A total of 26 patients were included in the study; the median age was 60.5 years (30 to 78); 19 (73%) women; and 4 patients with ECOG 0 and 22 – with ECOG 1. All patients were previously treated with the inclusion of oxaliplatin, irinotecan, fluoropyrimidines, 21 (81%) – bevacizumab, 6 (23%) – anti-EGFR antibodies, and 2 (7.7%) – regorafenib. The median for treatment courses was 4 (1–21), 11 (42.3%) patients were treated for 6 months or more. The two-month progression-free survival rate was 52% with a median progreesion-free survival rate of 4 months (95% CI 1.8–7.4 months). The median of total survival rate was 11 months (95% CI 5,2–16,8 months). Disease control was achieved in 60%. Neutropenia, nausea, vomiting, anemia, weakness prevailed among undesirable events associated with treatment (≥5 patients). The majority of complications were of the 1st–2nd degree. Among the undesirable events of the 3rd–4th degree, neutropenia was more common, while in 3 patients febrile neutropenia of the 3rd degree was registered.Conclusions. In the Russian population of patients with colorectal chemorefractory cancer, the drug FTD/TPI (TAS-102) shows efficacy and tolerability comparable to the RECOURSE registration study.

Objective: to identify factors associated with efficacy of an aflibercept-chemotherapy combination in patients with metastatic colon cancer. Materials and methods. This retrospective multicenter study was conducted in 20 clinics from 15 regions of the Russian Federation. The main efficacy outcome was progression-free survival (PFS). We performed univariate and multivariate analysis to assess the impact of various factors of PFS. Results. Two hundred and fifty-seven patients received aflibercept-containing chemotherapy; of them, 175 participants (68.1 %) received it as a second-line therapy. The objective response rate and median PFS were 18.7% and 5 months (95% confidence interval (CI) 4.2—5.8) respec -tively. The following factors were found to have a positive effect of PFS at multivariate analysis: grade I—II adverse events to aflibercept therapy (hazard ratio (HR) 0.58; 95 % CI 0.38—0.89; p = 0.01), therapy for concomitant diseases (HR 0.47; 95 % CI 0.29—0.76; p = 0.002), and ECOG performance status of 0 (HR 0.53; 95 % CI 0.34—0.81; p = 0.004). Patient with all 3 factors present had median PFS of 9 months, whereas patients without them demonstrated PFS of only 3 months (HR 1.9; 95 % CI 1.5—2.6; p <0.001). Conclusions. Satisfactory performance status, adequate therapy for concomitant diseases, and adverse events to aflibercept therapy were associated with better PFS in patients receiving aflibercept-containing chemotherapy.

Objective: to identify factors associated with efficacy of an aflibercept-chemotherapy combination in patients with metastatic colon cancer.Materials and methods. This retrospective multicenter study was conducted in 20 clinics from 15 regions of the Russian Federation. The main efficacy outcome was progression-free survival (PFS). We performed univariate and multivariate analysis to assess the impact of various factors of PFS.Results. Two hundred and fifty-seven patients received aflibercept-containing chemotherapy; of them, 175 participants (68.1 %) received it as a second-line therapy. The objective response rate and median PFS were 18.7% and 5 months (95% confidence interval (CI) 4.2—5.8) respec -tively. The following factors were found to have a positive effect of PFS at multivariate analysis: grade I—II adverse events to aflibercept therapy (hazard ratio (HR) 0.58; 95 % CI 0.38—0.89; p = 0.01), therapy for concomitant diseases (HR 0.47; 95 % CI 0.29—0.76; p = 0.002), and ECOG performance status of 0 (HR 0.53; 95 % CI 0.34—0.81; p = 0.004). Patient with all 3 factors present had median PFS of 9 months, whereas patients without them demonstrated PFS of only 3 months (HR 1.9; 95 % CI 1.5—2.6; p <0.001).Conclusions. Satisfactory performance status, adequate therapy for concomitant diseases, and adverse events to aflibercept therapy were associated with better PFS in patients receiving aflibercept-containing chemotherapy.

Purpose . To assess the incidence and severity of adverse events; to explore clinical factors associated with grade 3–4 non-hematologic toxicity; to assess the immediate efficacy and progression-free survival during treatment with the FOLFIRI regimen in combination with aflibercept in Russia. Materials and Methods . A retrospective multicenter study has been conducted with data collected from 20 clinics in 15 regions of Russia. There was no statistical hypothesis. Progression-free survival was the main efficacy criterion. The statistical analysis was performed using IBM SPPS Statistics v. 20 software. Results . FOLFIRI and Aflibercept combination was administered to 264 patients. The mean number of treatment cycles was 6 (1 to 29). The toxicity of aflibercept was addressed by dose reduction and dosing delay in 10.1 % and 11.4 % of patients, respectively, and dose reductions and dosing delays in any of FOLIFRI components were reported in 20.1 % of participants. The objective response rate was 20.3 %. The median progression-free survival in patients receiving second-line treatment was 6 months (95 % CI: 5.3–6.6 months). Seventy-two percent of patients experienced any grade of adverse events most of which were limited to grade 1–2 (62.1 %). Non-hematologic toxicity was reported in 64 % of patients (grade 3–4 in 17.9 %). Hematologic events were detected in only 17.9 % of patients. Multifactorial analysis has shown that drug therapy for concomitant diseases (OR 1.98, 95 % CI: 1.04–3.78, p = 0.037) and the number of chemotherapy lines prior to aflibercept (ОR 1.5, 95 % CI: 1.06–2.11, p = 0.02) were independent predictors of grade 3–4 non-hematologic toxicity. Conclusions . Objective response rate, progression-free survival, and frequency of toxicity-related aflibercept discontinuations in the Russian study with patients receiving aflibercept in combination with FOLFIRI regimen as a second-line treatment has shown the results that were comparable with VELOUR study. Comorbidities requiring drug treatment and the number of prior chemotherapy lines appear to be risk factors for grade 3–4 nonhematological toxicity events.