Efficacy and Safety of Approved First-Line Tyrosine Kinase Inhibitor Treatments in Metastatic Renal Cell Carcinoma: A Network Meta-Analysis

Manz, Kirsi M. ; Fenchel, Klaus; Eilers, Andreas; Morgan, Jonathan; Wittling, Kirsten and Dempke, Wolfram C. M. (14. December 2019): Efficacy and Safety of Approved First-Line Tyrosine Kinase Inhibitor Treatments in Metastatic Renal Cell Carcinoma: A Network Meta-Analysis. In: Advances in therapy, Vol. 37: pp. 730-744

Abstract

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.

• Item Type: Journal article
• Faculties: Medicine > Institute for Medical Information Processing, Biometry and Epidemiology
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0741-238X
• Language: English