Safety of bevacizumab in patients with advanced cancer: a meta-analysis of randomized controlled trials.
OBJECTIVE
We performed a meta-analysis on adverse events seen with bevacizumab to combine the existing evidence about its safety in patients with advanced cancer.


METHODS
A systematic literature search was conducted to identify published, randomized controlled trials of bevacizumab in cancer patients with data on adverse events available. The primary endpoint was "severe adverse event," a composite of grade 3 and 4 adverse events. Secondary endpoints for the exploratory analysis were individual adverse events. We used random-effects meta-analysis to combine data.


RESULTS
Thirteen eligible publications were identified and eight trials reported the primary endpoint. Compared with the control group, the bevacizumab group had a slightly higher risk for any severe adverse event (pooled relative risk, 1.10; 95% confidence interval [95% CI], 1.01-1.19). The pooled risk difference was 7% (95% CI, 1%-13%), with a number needed to harm of 14 treated patients. Exploratory analyses showed a statistically significant higher risk for eight of the 15 evaluated secondary endpoints: bevacizumab was associated with a fourfold higher risk for hypertension, epistaxis, and gastrointestinal hemorrhage/perforation; a threefold higher risk for any bleeding events; and a lower, but elevated risk for proteinuria, leukopenia, diarrhea, and asthenia. No statistically significant differences were found for any thrombotic event (arterial or venous), hemoptysis, cardiac event, thrombocytopenia, neutropenia, impaired wound healing, or death related to an adverse event.


CONCLUSIONS
Treatment with bevacizumab was associated with a slightly higher risk for any severe (grade 3 or 4) adverse event in patients with cancer. The result may impact individual benefit-risk assessments and policy guidelines.
Ludwig Boltzmann Institute of Health Technology Assessment, Vienna, Austria. sabine.geiger-gritsch@umit.at
Sabine
S
Geiger-Gritsch
Bjoern
B
Stollenwerk
Rebecca
R
Miksad
Beate
B
Guba
Claudia
C
Wild
Uwe
U
Siebert
D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D018450:Disease Progression; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab