Four RCTs (reported in six publications) were included in the review (2,277 patients, range 189 to 903); three phase III trials and one phase II trial. Two trials scored a 5 and two trials scored a 3 on the Jadad scale. All trials were conducted in the USA. There were some discrepancies between text, tables and figures regarding which data were used in the analysis.
A significant effect on progression-free survival was found in favour of sorafenib or sunitinib when compared with interferon-α (HR 0.47, 95% CI 0.32 to 0.71; p<0.001; two RCTs) and sorafenib or pazopanib when compared with placebo or interferon-α (HR 0.45, 95% CI 0.04 to 0.86; Ι²=0%, three RCTs). No between group differences were found for sorafenib and sunitinib compared with interferon-α or placebo (three RCTs), or sorafenib and pazopanib compared with placebo (two RCTs). Trials were not pooled for overall survival as completed data were not available in all trials.
The results of the indirect comparison (with interferon-α as the comparator) found a significant effect on progression-free survival in favour of sunitinib versus sorafenib (HR 0.47, 95% CI 0.32 to 0.71; p<0.001). No significant difference was found between sorafenib versus pazopanib with placebo as the comparator.