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First-line treatment in the management of advanced renal cell carcinoma: systematic review and network meta-analysis
Authors:James Larkin  Abby Paine  Grace Foley  Stephen Mitchell  Connie Chen
Institution:1. Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK;2. Zedediah Consulting, Wokingham, RG41 3AP, UK;3. Pfizer Ltd, Walton Oaks, Surrey, KT20 7NS, UK;4. Systematic Review Department, Abacus International, 6 Talisman Business Centre, Talisman Road, Bicester, Oxfordshire, OX26 6HR, UK;5. Pfizer Global Pharmaceuticals, 235 East 42nd Street, New York, NY 10015-5755, USA +1 212 733 2650;6. +1 646 441 4785;7. Connie.chen@Pfizer.com
Abstract:Objectives: To conduct a systematic review and network meta-analysis (NMA) to assess effectiveness of first-line treatments for advanced renal cell carcinoma (RCC).

Methods: Database searches were conducted to identify randomized controlled trials (RCTs) reporting results for eligible treatments. A fixed-effect Bayesian NMA was conducted to assess the relative effectiveness of treatments, with progression-free survival (PFS) reported as hazard ratios (HRs) and 95% credible intervals (CrIs).

Results: Eleven unique RCTs were suitable for inclusion in the NMA. In the base case, in terms of PFS, sunitinib was superior compared with bevacizumab + IFN-α (HR = 0.79, 95% CrI: 0.64 – 0.96), everolimus (HR = 0.70, 95% CrI: 0.56 – 0.87), sorafenib (HR = 0.56, 95% CrI: 0.40 – 0.77) and temsirolimus + bevacizumab (HR = 0.74, 95% CrI: 0.56 – 0.96). Although, the point values for the mean and median HRs were < 1.0, there was no significant difference in PFS between sunitinib and axitinib, pazopanib or tivozanib. Although sensitivity analyses impacted the results of the NMA, no treatment was significantly more efficacious than sunitinib.

Conclusion: Results from this analysis suggest that there is no treatment superior to the current benchmark treatment, sunitinib, in the management of advanced RCC in the first-line setting.

Keywords:meta-analysis  progression-free survival  renal cell carcinoma  systematic review
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