Clinical Outcomes and Adverse Events after First-Line Treatment in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis.

Four recent first-line clinical trials leveraging immune-oncology agents demonstrated an overall survival (OS) benefit relative to sunitinib. We aimed to provide formal comparisons among immune-oncology combinations in term of OS, progression-free survival (PFS), objective response rates (ORR) and treatment-related adverse events (AEs).

Pubmed database was searched for studies indexed from January 1, 2016 through March 6, 2021. Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included: CheckMate 214 (nivolumab plus ipilimumab [N+I]), KEYNOTE-426 (pembrolizumab plus axitinib [P+A]), CheckMate 9ER (nivolumab plus cabozantinib [N+C]) and KEYNOTE-581 (lenvatinib plus permbrolizumab [L+P]). OS represented the primary outcome. PFS, ORR and AEs represented secondary outcomes.

Overall, 3,320 patients were included. Regarding OS, N+C ranked first, followed by L+P, P+A and N+I. Regarding PFS and ORR, L+P ranked first, followed by N+C, P+A and N+I. Finally, N+I ranked first with respect to lowest grade 3+ AEs, followed by P+A, N+C and L+P. Differences in follow-up duration, risk grouping and nephrectomy rates distinguish the studies.

N+C may provide the most favorable OS, L+P the most favorable PFS and ORRs, while N+I the lowest toxicity. Population differences may potentially undermine the generalizability and the robustness of findings.

The Journal of urology. 2021 Sep 21 [Epub ahead of print]

Luigi Nocera, Pierre I Karakiewicz, Mike Wenzel, Zhe Tian, Shahrokh F Shariat, Fred Saad, Felix K H Chun, Alberto Briganti, Anil Kapoor, Aly-Khan Lalani

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany., Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada.

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