Is antiangiogenic therapy necessary for patients with metastatic colorectal cancer (mCRC) and mutation in the BRAF gene? Results of the systematic review and meta-analysis.

Abstract

88 Background: There are no direct prospective randomized studies supporting the need for antiangiogenic drugs in the treatment of patients with the m BRAF mCRC. However, subgroup analysis of different studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy anti-angiogenic targeted therapy with chemotherapy and chemotherapy alone in patients with m BRAF mCRC in terms of progression free survival (PFS), and overall survival (OS). Methods: We performed a search of all prospective randomized phase III studies in PubMed, ASCO and ESMO congresses for all years before September, 2020, compared chemotherapy (CT) plus bevacizumab or aflibercept or ramucirumab and CT alone at the first-line or second-lines with information of the BRAF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary–HR for OS and 95%CI. Fixed effects were used for analysis. Meta-analysis was conducted by "Review Manager" Ver. 5.3. Results: We identified 4 trials (AVF2107g, AGITG MAX, VELOUR and RAISE), which included 120 patients with mBRAF (anti-angiogenic plus CT–65 (54%) and CT alone–55 (46%). According to results of the meta-analysis there was a tendency for significant improvement in PFS (HR 0.64, 95% CI 0.4-1.02; p = 0.06; I2 = 0%, p for heterogeneity 0.7; 53trials) and significant improvement in OS (HR 0.51, 95% CI 0.32-0.82; p = 0.005; I2 = 0%, p for heterogeneity 0.52; 4 trials) in group of ani-angiogenic therapy. Conclusions: Addition of anti-angiogenic therapy to chemotherapy showed improvement in the PFS and OS in pts with m BRAF compared with chemotherapy alone. A prospective randomized trial is needed to determine the optimal regimen of systemic therapy for pts with m BRAF mCRC.