e15007 Background: Afl is one of the antiagiogenic agents used for the treatment for mCRC. Cardiovascular toxicity of Afl is shown to be a main reason of the drug discontinuation but there are no studies on factors associated with nonhem adverse events(AEs). The aim of the study was to define clinical factors associated with the development of Gd.3-4 nonhem AEs. Methods: Pts with mCRC treated with FOLFIRI+Afl were included in a multicenter prospective base from 2016-18. Multivariative regression analysis was performed with Chicago, IL v.22.0. Factors studied included demographic, disease characteristics, data about concomitant diseases(CD) and concomitant medications. Results: 278 pts with mCRC from 18 centers were included. Mean age – 58.7, 48.6% were male, mean number of metastases– 2. ECOG 0-1–97.5%pts. RASm had 133 (47.8%) pts. Afl+FOLFIRI was used as the 2nd line therapy–in 67.6%. CD were in 194 (69.8%), cardiovascular–in 175 (62.9%). ORR(CR+PR)17.3%, SD-43.9%. MedPFS was 6.0 mos. Afl discontinuation due to AEs 11.9%. AE were reported in 201 (72.3%), Gd3-4 – in 69 (24.8%); nonhem AEs – in 178 (64%), Gd3-4–52 (18.8%)pts. Among Gd3-4 nonhem AEs were arterial hypertension Gd1-2–77 (27.7%), Gd3-4-in 36 (12.9%), vomiting Gd1-2–45 (16.2%), diarrhea Gd1-2–in 32 (11.5%), asthenia Gd1-2 –in 29 (10.4%), hepatotoxicity Gd1-2–in 2(5%), thrombosis–in 2 (5%) pts. Multivariate regression analysis showed that among the factors studied number of lines of treatment (OR1.4,95%CI1.1-2.1,p=0.03) and CD requiring medical support (OR 2.0,95%CI1.1-3.7,p=0.03) were found as independent factors of nonhem AE Gd3-4 development. ACE-inhibitors (OR2.2,95%CI1.2-4.3,p=0.02), calcium-channel blockers (CCB)(OR4.1,95%CI1.6-10.4,p=0.003 ) were the medical drugs considered to be significant. Conclusions: Number of lines and CD requiring medical support, especially with ACE-inhibitors or CCB, identifies a significant risk of developing cardiovascular non-hem AEs Gd3-4 with FOLFIRI + Afl.

In recent years there has been strong progress in the treatment of metastatic colorectal cancer (mCRC) patients. The gain of the median of the overall survival (mOS) rate was more than doubled due to the introduction in the clinical practice of new compounds, the work of a multidisciplinary team, the timely registration of the disease progress, prescription of combined chemotherapy in the second line. The article presents the immediate and long-term results of a comparative study carried out on the basis of Oncology Centers, 122 mCRC patients were included, most of these patients - 87(71,3%) had surgery firstly, after that all patients were treated with standard chemotherapy FOLFOX-4 in the first-line treatment and FOLFIRI in the second line treatment, two groups of patients in the first and second lines of treatment received a combination of chemotherapy and targeted agents (bevacizumab, cetuximab), depending on the biological properties of the tumor (RAS-gene mutation status). The following results: metastatic progression-free survival (mPFS) for FOLFOX-4 group accounted for 12.0(±1.2) months; FOLFOX-4 + Bevacizumab - 20.3(±1.2) months, FOLFOX-4 + cetuximab - 22.0(± 2.0) months; mPFS for second-line therapy for FOLFIRI + bevacizumab group amounted to 24.0(± 3.1) months, FOLFIRI + cetuximab 22.5(±2.5) months, FOLFIRI-1 8.0(±2.4) months, FOLFIRI-2 6.4(±2.6) months; mOS for FOLFOX-4 group was 49.5(±2.5) months; FOLFOX-4 + Bevacizumab - 45.8(±2.1) months; FOLFOX-4 + cetuximab - 37.4(± 2.0) months; mOS for second-line therapy for FOLFIRI + bevacizumab group was 37.8(± 2.1) months, FOLFIRI + cetuximab - 31.5(± 2.3) months, FOLFIRI-1 - 26.3(± 1.8) months, FOLFIRI-2 - 26.2(± 1.9) months. The adverse events during the treatment of patients are reported.

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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.