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A Meta-analysis

Shobha Rani Nalluri, MD; David Chu, MD; Roger Keresztes, MD; Xiaolei Zhu, MD, PhD; Shenhong Wu, MD, PhD

JAMA. 2008;300(19):2277-2285.

Context  Venous thromboembolism is one of the leading causes of morbidity and mortality in patients with cancer. Concerns have arisen regarding the risk of venous thromboembolism with the novel antiangiogenic agent bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in venous thromboembolism is controversial.

Objective  To assess the overall risk of venous thromboembolism associated with the use of bevacizumab, a systematic review and meta-analysis of published randomized controlled trials was performed.

Data Sources  The databases of PubMed and Web of Science were searched for articles published in the English language from January 1966 until January 2008 and abstracts presented at American Society of Clinical Oncology conferences held between January 2000 and January 2008 were searched to identify relevant clinical trials.

Study Selection and Data Extraction  Eligible studies included prospective randomized controlled trials in which standard antineoplastic therapy was used with and without bevacizumab and data on venous thromboembolism were available. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies.

Data Synthesis  A total of 7956 patients with a variety of advanced solid tumors from 15 randomized controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidences of all-grade and high-grade venous thromboembolism were 11.9% (95% CI, 6.8%-19.9%) and 6.3% (95% CI, 4.8%-8.3%), respectively. Patients treated with bevacizumab had a significantly increased risk of venous thromboembolism with an RR of 1.33 (95% CI, 1.13-1.56; P < .001) compared with controls. The risk was significantly increased for both all-grade and high-grade venous thromboembolism. In addition, the risk was similarly increased for bevacizumab at 2.5 mg/kg per week (low dose; RR, 1.31 [95% CI, 1.08-1.60]; P = .007) and 5 mg/kg per week (high dose; RR, 1.31 [95% CI, 1.02-1.68]; P = .04).

Conclusion  The use of bevacizumab was significantly associated with an increased risk of developing venous thromboembolism in cancer patients receiving this drug.

Author Affiliations: Division of Medical Oncology, Department of Medicine, Stony Brook University, Stony Brook, New York (Drs Nalluri, Chu, Keresztes, and Wu); and Kidney Doctor PLLC, Port Jefferson Station, New York (Dr Zhu).

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