Twenty three studies were included in the review: four phase 3 randomised controlled trials (RCTs) (n=2,540); 17 phase 2 case series (n=1,352); and two expanded-access case series (n=4,102). Sample sizes ranged from 16 to 2,954. Studies were reported as being full-text, abstract or presentation slides; the method of reporting for each study was not provided.
Incidence: Incidence of all-grade bleeding events was 16.7% (95% CI 12.7 to 21.5; 17 studies). Incidence of high-grade events was 2.4% (95% CI 1.6 to 3.9; 18 studies). There was evidence of significant heterogeneity (I2>78%, p<0.0001 for both analyses). Subgroup analyses found a significantly higher incidence of all-grade bleeding events among sorafenib trials that included renal-cell cancer patients (20.6%, 95% CI 14.1 to 29.2) compared with non-renal-cell cancer patients (7.6% 95% CI 5.4 to 10.5, p=0.018). No other differences between subgroups were found.
Relative risk: Sunitinib and sorafenib were associated with a statistically significant increase in the risk of all-grade bleeding compared to placebo or interferon (RR 2.0, 95% CI 1.14 to 3.49, p=0.015; four RCTs). There was no statistically significant difference between the groups for high-grade bleeding events (four RCTs). There was evidence of significant heterogeneity (I2 =81.7%, p<0.0001) for all-grade events, but not for high-grade events. Subgroup analyses found no statistically significant differences.
There was no evidence of publication bias for any of the analyses.