Background Advanced renal cell carcinoma (RCC) presents multiple therapeutic alternatives. Recently, tivozanib has been authorised in this indication.
Purpose To perform a network meta-analysis (NMA) to provide a comprehensive treatment comparison of the efficacy of first-line antiangiogenic treatment in RCC.
Material and methods A review in the Pubmed database and the European Medicines Agency was done. Inclusion criteria: pivotal randomised clinical trials (CT), including antiangiogenic drugs (sunitinib, pazopanib, sorafenib, tivozanib, interferon and bevacizumab) in treatment-naive patients with RCC, with the most mature data of progression-free survival (PFS). Subgroups of CT with pre-treated and treatment-naive patients were assessed. Exclusion criteria: pivotal CT without a comparator common to the alternatives evaluated. The evaluated outcome was PFS. NMA combined direct and indirect evidence to calculate pooled hazard ratios (HR) by Bayesian methods. Fixed and random effects were evaluated. Models were compared using deviance information criteria (DIC) statistics. The consistency of NMA was assessed by node-splitting models to assess agreement of direct and indirect estimations.
Results Seven eligible CT were selected. Three CT included pre-treated patients and treatment-naive patients. No statistical interaction was found between pretreated and treatment-naive patients, so global results were used for the analysis. Inclusion criteria involved 0–1 (ECOG) performance status in all CT. Sorafenib studies included patients with life expectancy ≥3 months. The value of DIC was found more favourable for the fixed-effects model. NMA was consistent because node-splitting models detect no statistical differences between direct and indirect evidence. Regarding sunitinib (treatment with the greatest magnitude of effect), HR for PFS were: 0.39 (CI 95% 0.30 to 0.51) vs. placebo, 0.56 (0.47 to 0.66) vs. interferon, 0.74 (0.56 to 0.97) vs. sorafenib, 0.89 (0.70 to 1.1) vs. bevacizumab plus interferon, 0.92 (0.65 to 1.30) vs. tivozanib, and 0.93 (0.80 to 1.10) vs. pazopanib. CI 95% for HRs among bevacizumab plus interferon, pazopanib, sunitinib and tivozanib included a neutral value. Tivozanib (HR 0.74; 0.56 to 0.97) and sunitinib (0.80; 0.64 to 0.99) – but no other antiagiogenics – showed benefit over sorafenib. Statistically significant benefit was found between all drugs over interferon and placebo.
Conclusion The NMA provided a review of the relative efficacy of current antiangiogenic alternatives for RCC in terms of PFS. Bevacizumab plus interferon, pazopanib, sunitinib and tivozanib showed no differences. Sorafenib was inferior to sunitinib and tivozanib.
References and/or acknowledgements None.
No conflict of interest.
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