Safety of bevacizumab in patients with malignant gliomas: a systematic review

Abstract

Angiogenesis has recently become a major target for the development of new antineoplastic drugs. The most serious adverse events linked to angiogenesis inhibitors are venous or arterial thromboembolism and haemorrhage. Thus, there is need to define with more certainty the impact of these new drugs in terms of adverse effects in neurological patients. The aim of the study is to assess the risk of venous thromboembolism (VTE) and bleeding in patients with malignant gliomas treated with bevacizumab with or without concomitant anticoagulant therapy. A review of published literature was performed in Medline, from which 476 records were identified. A total of 27 full-text articles, including retrospective analyses, retrospective reviews, and open label trials, were assessed for eligibility. The investigated drugs included bevacizumab alone, bevacizumab plus chemotherapy with/without concomitant radiation therapy; only two articles dealt with bevacizumab in association with anticoagulant treatment. A total of 2,208 patients with malignant gliomas, were identified and included in the analysis. From data it appears that patients receiving bevacizumab had a major risk of developing VTE that increased when bevacizumab is associated with radio-chemotherapy (4.27 vs 7.46 %). Regarding bleeding, data showed that patients treated with anticoagulant had a significantly increased risk of severe central nervous system (CNS) bleeding compared to patients not receiving anticoagulant therapy (0.6 vs 8.2 %). The use of bevacizumab combined with chemo-radiotherapy seems to be associated with a higher risk for VTE compared to patients receiving antiangiogenic therapy alone. The associated use of anticoagulants and bevacizumab far increases the risk of developing CNS and non-CNS bleeding higher than grade 3, compared to patients receiving bevacizumab alone.

Tumor-Specific D-Dimer Concentration Ranges and Influencing Factors: A Cross-Sectional Study

“…D-dimer did not appear to be influenced by radio/chemotherapy based on our results. The use of bevacizumab combined with chemoradiotherapy is associated with a higher risk of VTE compared with antiangiogenic therapy alone [20, 21]. Among 29 patients in our study who underwent radiotherapy and 101 who received chemotherapy, none was given bevacizumab at any point in his or her treatment.…”

International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer

“…125 Major bleeding was not signifi cantly increased, but the CI was large (HR 4·2, 95% CI 0·48-36), and all major bleeds were intracranial. Since 2013, one meta-analysis 126 (2208 patients) reported that the proportion of patients with VTE was 4·3% with bevacizumab alone, 4·2% when co-administered with chemotherapy, and 7·5% with the addition of radiotherapy, although these results were not statistically signifi cant. However, severe CNS bleeding was considerably more prevalent in patients receiving anticoagulation (8·2% with anticoagulation vs 0·6% without anticoagulation; p<0·001).…”

High rates of venous thromboembolic events in patients undergoing systemic therapy for urothelial carcinoma: A systematic review and meta-analysis

“…[20] The pooled VTE rate in the 4 studies that used bevacizumab in the current study was 20%, which is significantly higher than bevacizumab-associated VTE rates reported in multiple other cancers. [20, 21] Simonietti et al . conducted a meta-analysis on bevacizumab-associated VTE in malignant glioma and reported a VTE rate of 7.5% in patients receiving bevacizumab and chemoradiation versus 4.3% in patients receiving bevacizumab alone.…”

“…conducted a meta-analysis on bevacizumab-associated VTE in malignant glioma and reported a VTE rate of 7.5% in patients receiving bevacizumab and chemoradiation versus 4.3% in patients receiving bevacizumab alone. [21] A meta analysis by Nalluri et al . reported a bevacizumab-associated VTE rate of 11.9% among patients with multiple solid tumor types, including colorectal cancer, non-small cell lung cancer, breast cancer, and renal cell carcinoma.…”