Results on efficacy and safety of cancer treatment with or without tumor necrosis factor-related apoptosis-inducing ligand-related agents: A meta-analysis

This meta-analysis aimed to evaluate the currently available evidence on the efficacy and safety of cancer treatment with or without tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-related agents. We conducted a systematic search through Medline, Cochrane Library and EMBASE electronic databases and manually searched the Journal of Clinical Oncology to identify randomized controlled trials (RCTs) conducted between 1995 and 2013 comparing the efficacy and safety results of cancer treatment with and without TRAIL-related agents. The methodological quality of the included RCTs was assessed by the Cochrane Risk of Bias assessment tool. The outcome measurements included objective response rate (ORR), clinical benefit rate (CBR)/disease control rate (DCR) and adverse events (AEs). The relevant data were analyzed using Review Manager 5.2 software. Grading of Recommendations Assessment Development and Evaluation was used to assess the quality of evidence and grade of recommendation. Four RCTs, including a total of 596 patients, were ultimately selected and analyzed. There were no statistically significant differences among the 4 RCTs regarding ORR [relative risk (RR)=0.92, 95% confidence interval (CI): 0.73-1.15, P=0.45], CBR/DCR (RR=0.92, 95% CI: 0.81-1.05, P=0.21), progression-free survival [hazard ratio (HR)=0.89, 95% CI: 0.75-1.05, P=0.16], overall survival (HR=0.90, 95% CI: 0.74-1.09, P=0.27), number of patients with any AEs (RR=0.99, 95% CI: 0.96-1.03, P=0.77), number of patients with any severe AEs (RR=0.95, 95% CI: 0.78-1.55, P=0.58), number of patients with ≥grade 3 AEs (RR=1.13, 95% CI: 0.93-1.38, P=0.22) and number of fatal AEs (RR=1.14, 95% CI: 0.71-1.81, P=0.59). The quality of evidence was considered to be moderate and the recommendation grades were weak. In conclusion, the benefits of TRAIL-related agents in the treatment of cancer patients remain uncertain and further clinical trials are required.