Risk of high-grade bleeding in patients with cancer treated with bevacizumab: a meta-analysis of randomized controlled trials.
OBJECTIVE
High-grade bleeding is a serious adverse event associated with bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor and widely used in the current cancer treatments. The aim of this study was to gain a better understanding of the overall incidence and risk of high-grade bleeding in cancer patients who receive bevacizumab therapy.


METHODS
We performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, Embase, and American Society of Clinical Oncology conferences. Overall relative risks (RRs), incidence rates, and 95% confidence intervals (CIs) were calculated using a random-effects model. The primary clinical endpoint was high-grade bleeding (grade 3 or above).


RESULTS
A total of 14,277 patients with a variety of solid tumors from 22 RCTs were included in the present analysis. The addition of bevacizumab to cancer chemotherapy significantly increased the risk of high-grade bleeding (RR 1.60, 95% CI 1.19-2.15), with RRs of high-grade bleeding among patients receiving bevacizumab at 2.5 and 5 mg/kg per week of 1.27 (95% CI 0.95-1.71) and 3.02 (95% CI 1.85-4.95), respectively. The overall incidence of high-grade bleeding among patients receiving bevacizumab was 2.8% (95% CI 2.1-3.8). Higher risks were observed in patients with non-small-cell lung cancer (RR 3.41, 95% CI 1.68-6.91), renal cell carcinoma (RR 6.37, 95% CI 1.43-28.33), and colorectal cancer (RR 9.11, 95% CI 1.70-48.79) who were receiving bevacizumab at 5 mg/kg per week.


CONCLUSIONS
Among the patients included in the trials analyzed in this meta-analysis, the addition of bevacizumab to cancer chemotherapy significantly increased the risk of high-grade bleeding. The risk may be dose-dependent and may vary with tumor type.
Department of Infectious diseases, Changzheng Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
Xiao Feng
XF
Hang
Wen Sheng
WS
Xu
Jun Xue
JX
Wang
Lei
L
Wang
Hai Guang
HG
Xin
Rui Qi
RQ
Zhang
Wu
W
Ni
D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab; D004305:Dose-Response Relationship, Drug; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
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