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

• Published in: Advances in therapy Vol. 37; no. 2; pp. 730 - 744
• Main Authors: Manz, Kirsi M., Fenchel, Klaus, Eilers, Andreas, Morgan, Jonathan, Wittling, Kirsten, Dempke, Wolfram C. M.
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.02.2020
• Subjects: Adult; Aged; Aged, 80 and over; Anilides - therapeutic use; Antineoplastic Agents - therapeutic use; Carcinoma, Renal Cell - drug therapy; Cardiology; Endocrinology; Female; Humans; Internal Medicine; Kidney Neoplasms - drug therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Metastasis - drug therapy; Network Meta-Analysis; Oncology; Original Research; Pharmacology/Toxicology; Phenylurea Compounds - therapeutic use; Progression-Free Survival; Protein Kinase Inhibitors - therapeutic use; Pyridines - therapeutic use; Pyrimidines - therapeutic use; Quinolines - therapeutic use; Rheumatology; Sulfonamides - therapeutic use; Sunitinib - therapeutic use; Metastatic renal cell carcinoma; Adverse event; Network meta-analysis; Randomised controlled trials; Progression-free survival; Tyrosine kinase inhibitors
• ISSN: 0741-238X; 1865-8652
• DOI: 10.1007/s12325-019-01167-2

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.