• Wallis Christopher J D CJD Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada., Zachary Klaassen, Bimal Bhindi, Xiang Y Ye, Thenappan Chandrasekar, Ann M Farrell, Hanan Goldberg, Stephen A Boorjian, Bradley Leibovich, Girish S Kulkarni, Prakesh S Shah, Georg A Bjarnason, Heng Daniel Y C DYC Department of Oncology, University of Calgary, Calgary, Alberta, Canada., Raj Satkunasivam, and Antonio Finelli.
• Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
• Eur. Urol. 2018 Sep 1; 74 (3): 309-321.

ContextIn the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents.ObjectiveTo indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC.Evidence AcquisitionMedline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes.Evidence SynthesisIn total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48% chance that nivolumab plus ipilimumab was the preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs.ConclusionsCabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials.Patient SummaryThere are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation.Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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