Journal
ADVANCES IN THERAPY
Volume 37, Issue 2, Pages 730-744Publisher
SPRINGER
DOI: 10.1007/s12325-019-01167-2
Keywords
Adverse event; Metastatic renal cell carcinoma; Network meta-analysis; Progression-free survival; Randomised controlled trials; Tyrosine kinase inhibitors
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Introduction This network meta-analysis aims to deliver an up-to-date, comprehensive efficacy and toxicity comparison of the approved first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC) in order to provide support for evidence-based treatment decisions. Previous NMAs of first-line mRCC treatments either predate the approval of all the first-line TKIs currently available or do not include evaluation of safety data for all treatments. Methods We performed a systematic literature review and network meta-analysis of phase II/III randomised controlled trials (RCTs) assessing approved first-line TKI therapies for mRCC. A random effects model with a frequentist approach was computed for progression-free survival (PFS) data and for the proportion of patients experiencing a maximum of grade 3 or 4 adverse events (AEs). Results The network meta-analysis of PFS demonstrated no significant differences between cabozantinib and either sunitinib (50 mg 4/2), pazopanib or tivozanib. The network meta-analysis indicated that in terms of grade 3 and 4 AEs, tivozanib had the most favourable safety profile and was associated with significantly less risk of toxicity than the other TKIs. Conclusion These network meta-analysis data demonstrate that cabozantinib, sunitinib, pazopanib and tivozanib do not significantly differ in their efficacy, but tivozanib is associated with a more favourable safety profile in terms of grade 3 or 4 toxicities. Consequently, the relative toxicity of these first-line TKIs may play a more significant role than efficacy comparisons in treatment decisions and in planning future RCTs.
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