Kidney Cancer Research Network of Canada (KCRNC) consensus statement on the role of adjuvant therapy after nephrectomy for high-risk, non-metastatic renal cell carcinoma: A comprehensive analysis of the literature and meta-analysis of randomized controlled trials

Pierre I. Karakiewicz, Emanuele Zaffuto, Anil Kapoor, Naveen S. Basappa, Georg A. Bjarnason, Normand Blais, Rodney H. Breau, Christina Canil, Darrel Drachenberg, Sebastien J. Hotte, Claudio Jeldres, Michael A.S. Jewett, Wassim Kassouf, Christian Kollmannsberger, Luke T. Lavallée, Ranjena Maloni, Francois Patenaude, Frédéric Pouliot, M. Neil Reaume, Robert Sabbagh, Bobby Shayegan, Alan So, Denis Soulières, Simon Tanguay, Lori Wood, Marco Bandini

Abstract


Introduction: The Kidney Cancer Research Network of Canada (KCRNC) collaborated to prepare this consensus statement about the use of target agents as adjuvant therapy in patients with nonmetastatic renal cell carcinoma (nmRCC) after nephrectomy. We reviewed the published data and performed a meta-analysis of studies that focused on vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).

Methods: A systematic literature search identified seven trials on adjuvant target therapy in nmRCC. Three trials, the ASSURE, S-TRAC, and PROTECT, focused on VEGFR TKIs and represented the focus of the study, including a meta-analysis combining their data on disease-free survival (DFS) and overall survival (OS).

Results: The ASSURE trial showed no DFS or OS benefit of TKIs over placebo after one year of adjuvant sorafenib or sunitinib. In contrast, the S-TRAC trial showed improved DFS after one year of adjuvant sunitinib using central review process, but not using investigator review process. No OS benefit was recorded in either study. Recently, the PROTECT trial also showed no DFS or OS benefit when one year of adjuvant pazopanib was compared to placebo. Meta-analyses of the pooled DFS and OS estimates from all three trials resulted in DFS and OS hazard ratios of 0.87 (95% confidence interval [CI] 0.73‒1.04) and 1.04 (95% CI 0.89‒1.22), respectively.

Conclusions: Data from three available clinical trials of adjuvant VEGFR TKIs vs. placebo do not currently support the use of adjuvant TKI therapy as standard of care after nephrectomy for nmRCC. At this time, adjuvant TKI-based adjuvant therapy is not recommended for routine use after nephrectomy for high-risk nmRCC, but highly motivated patients may benefit from a discussion with their oncologist regarding the risks and benefits of adjuvant TKI.


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DOI: http://dx.doi.org/10.5489/cuaj.5187