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Introduction: targeted anti‑angiogenic drugs are the integral component of systemic therapy for metastatic colorectal cancer. To date, there have been no prospective studies that would directly answer the question of the need to add anti‑ angiogenic agents to chemotherapy for BRAF‑mutated metastatic colorectal cancer. We performed a systematic review and meta‑analysis to evaluate the efficacy of adding anti‑angiogenic therapy to chemotherapy in patients with metastatic colorectal cancer harboring a mutation in the BRAF gene. Materials and methods: We searched for articles and abstracts in the PubMed, ASCO and ESMO databases, published before September 2020 and containing information on the results of prospective randomized trials comparing the combination of anti‑angiogenic agents (bevacizumab, aflibercept or ramucirumab) in the first‑or second‑line therapy for metastatic colorectal cancer, which indicate the efficacy depending on the presence of mutations in the BRAF gene. The primary endpoint was the risk ratio (RR) for progression or death with a 95 % confidence interval (95 % CI). The meta‑analysis was carried out using the Review Manager, version 5.3.Results: 4 studies met the selection criteria (AVF2107 g, AGITG MAX, VELOR and RAISE), which included data from 120 patients with the BRAF mutation, 65 (54 %) patients received a combination of chemotherapy with an anti‑angiogenic agent, and 55 (46 %) patients received only chemotherapy. The meta‑analysis showed improved progression‑free survival (RR 0.64, 95 % CI 0.4–1.02; p = 0.06; I 2 = 0 %, p for heterogeneity = 0.7; 3 studies) and overall survival (RR 0.51, 95 % CI 0.32–0.82; p = 0.005; I 2 = 0 %, p for heterogeneity = 0.54; 4 studies) in the group treated with anti‑angiogenic agents.Conclusions: the combination of chemotherapy with anti‑angiogenic agents in the first‑or second‑line therapy improves progression‑free survival and overall survival in patients with BRAF‑mutated metastatic colorectal cancer. Prospective randomized trials in this patient population are needed to determine the optimal first‑line treatment regimen.

Objective: to assess the frequency of liver resections in patients with metastatic colon cancer and isolated non-resectable liver metastases receiving FOLFOXIRI. Materials and methods. In this single-center non-randomized prospective study, we assessed the frequency of liver resections. According to the statistical hypothesis, the frequency of R0-resections in patients with metastatic colon cancer receiving FOLFOXIRI is between 11 % and 33 % (mean 20 %); to increase it up to 50 % in patients with isolated metastatic lesions in the liver, we had to recruit 20 patients (with β = 0.9 and a = 0.05). We enrolled 20 patients with potentially resectable metastases and 22 patients with non-resectable metastases. The primary endpoint was the frequency of R0 liver resections; secondary endpoints included objective response rate, progression-free survival, overall survival, and tolerability of therapy. Patients receiving targeted therapy (according to the tumor mutation status) were also included in the study.Results. Objective response was observed in 32 out of 42 patients (76 %) (in 17 out of 20 participants (85 %) with potentially resectable metastases), whereas progressive disease was registered in 2 patients (5 %). Radical resection of organs affected by metastasis was performed in 19 out of 42 patients (45 %): 15 out of 20 (75 %) in the group with potentially resectable metastases and 4 out of 22 (18 %) in the group with non-resectable metastasis (р <0.01). At a median follow-up of 11 months (range: 1–32 months), median progression-free survival was 10 months (95 % confidence interval (CI) 8.9–11.1), while median length of life was 34 months (95 % CI 21.3–46.7). Median overall survival was 34 months in patients that had undergone metastasectomy vs 19 months in patients that had no metastasectomy (hazard ratio 0.7; 95 % CI 0.01–0.70; p = 0.02).Conclusions. FOLFOXIRI increased the frequency of metastasectomy in patients with potentially resectable liver metastases from colon cancer, which was associated with a pronounced increase in the length of life.

Introduction. Based on the subgroup analysis of the TRIBE study FOLFOXIRI with bevacizumab is the recommended option for patients (pts) with mBRAF metastatic colorectal cancer (mCRC) in the 1st line. However, subgroup analysis of other studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy FOLFOXIRI and doublets with targeted therapy in pts with mBRAF mCRC in terms of progression free survival (PFS), objective response rate (ORR) and overall survival (OS).Methods. We performed a search of all prospective randomizes studies in PubMed, ASCO and ESMO congresses for all years before May, 2020, compared FOLFOXIRI plus bevacizumab or anti-EGFR antibodies and FOLFOX or FOLFIRI with targeted agents at the 1st line with information of the BRAF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary – HR for OS and odds ratio (OD) for ORR. Fixed effects were used for analysis. Meta-analysis was conducted by Review Manager Ver. 5.3.Results. We identified 6 trials (CHARTA, STEAM, TRIBE, TRIBE2, VISNU, METHEP2), which included 158 pts with mBRAF (FOLFOXIRI – 82 (52%) and doublets – 76 (48%). According to results of the meta-analysis there was a tendency for higher ORR in pts with FOLFOXIRI (OR 2.07, 95% CI 0.61–7.06; p = 0.24; I2 = 27%, p for heterogeneity 0.26; 3 trials). However we didn’t find any significant improvement in PFS (HR 0.89, 95% CI 0.64–1.23; p = 0.48; I2 = 0%, p for heterogeneity 0.63; 5 trials) or OS (HR 0.9, 95% CI 0.37–1.19; p = 0.048; I2 = 71%, p for heterogeneity 0.06; 2 trials) in the group of triplet.Conclusions. FOLFOXIRI with targeted therapy did not show significant improvement in the PFS and OS in pts with mBRAF compared with FOLFOX or FOLFIRI with targeted antibodies. A prospective randomized trial is needed to determine the optimal chemotherapy regimen at the 1st line for pts with mBRAF mCRC.

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