Is it necessary to add anti-angiogenic therapy to chemotherapy in patients with metastatic colorectal cancer and BRAF mutation? The systematic review and meta-analysis results

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.