Metastatic Renal Cell Cancer Treatments: An Indirect Comparison Meta-Analysis

Background:Treatment for metastatic renal cell cancer (mRCC) has advanced dramatically withunderstanding of the pathogenesis of the disease. New treatment options may provide improvedprogression-free survival (PFS). We aimed to determine the relative effectiveness of new therapiesin this field.Methods:We conducted comprehensive searches of 11 electronic databases from inception toApril 2008. We included randomized trials (RCTs) that evaluated bevacizumab, sorafenib, andsunitinib. Two reviewers independently extracted data, in duplicate. Our primary outcome wasinvestigator-assessed PFS. We performed random-effects meta-analysis with a mixed treatmentcomparison analysis.Results:We included 3 bevacizumab (2 of bevacizumab plus interferon-a [IFN-a]), 2 sorafenib, 1sunitinib, and 1 temsirolimus trials (total n = 3,957). All interventions offer advantages for PFS.Using indirect comparisons with interferon-α as the common comparator, we found that sunitinibwas superior to both sorafenib (HR 0.58, 95% CI, 0.38–0.86, P = < 0.001) and bevacizumab + IFNa(HR 0.75, 95% CI, 0.60–0.93, P = 0.001). Sorafenib was not statistically different from bevacizumab+IFN-a in this same indirect comparison analysis (HR 0.77, 95% CI, 0.52–1.13, P = 0.23). Usingplacebo as the similar comparator, we were unable to display a significant difference betweensorafenib and bevacizumab alone (HR 0.81, 95% CI, 0.58–1.12, P = 0.23). Temsirolimus providedsignificant PFS in patients with poor prognosis (HR 0.69, 95% CI, 0.57–0.85).Conclusion:New interventions for mRCC offer a favourable PFS for mRCC compared tointerferon-α and placebo.