Risk of Treatment-related Mortality with Sorafenib in Patients with Cancer

Abstract

<b>Background:</b> Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growthfactor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis todetermine the overall risk of FAEs associated with sorafenib. <br/><b>Methods</b>: Databases, including PubMed, Embaseand Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetingswere searched to identify relevant studies. Eligible studies included randomized controlled trials evaluatingsorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95%confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed accordingto tumor type and therapy regimen. <br/><b>Results</b>: 13 trials recruiting 5,546 patients were included in our analysis.The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenibhad a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen.A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99;P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs werehemorrhage (8.6%) and thrombus or embolism (4.9%). <br/><b>Conclusions</b>: It is important for health care practitionersto be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.