Bleeding risk in cancer patients treated with sorafenib: A meta-analysis of randomized controlled trials

Objective: Sorafenib, an oral vascular endothelial growth factor receptor tyrosine-kinase inhibitor, has become a cornerstone in the treatment of various malignancies. However, concerns have arisen regarding the risk of hemorrhage with sorafenib use. Nevertheless, the contribution of sorafenib to hemorrhage and the underlying risk factors remains unclear. Materials and Methods: We performed a meta-analysis to determine the incidence and risk of hemorrhage associated with sorafenib treatment. Multiple databases were searched to identify relevant studies. The analysis included randomized controlled trials (RCTs) that directly compared cancer patients treated with or without sorafenib. Statistical analyses were conducted to determine the overall incidence, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effect models. Results: Ten RCTs involving 4720 patients were included in the analysis. Overall, the incidence rates of all- and high-grade hemorrhage in patients receiving sorafenib were 9.89% (95% CI: 8.73u11.18%) and 2.86% (95% CI: 2.25u3.63%), respectively. Sorafenib treatment increased the risk of all-grade hemorrhage in patients compared to control treatment (RR: 1.99; 95% CI: 1.59u2.49; P < 0.00001), but did not increase the incidence of high-grade hemorrhage (RR: 1.42; 95% CI: 0.95u2.12; P = 0.09). Subgroup analysis showed no significant increase in the risk of hemorrhage between patients with various malignancies or concurrent treatment. No evidence of publication bias was observed. Conclusion: In patients with malignancy, sorafenib treatment combined with standard treatment significantly increases the risk of low-grade hemorrhagic events.