Pierre I Karakiewicz1, Emanuele Zaffuto1,2, Anil Kapoor3, Naveen S Basappa4, Georg A Bjarnason5, Normand Blais6, Rodney H Breau7, Christina Canil8, Darrel Drachenberg9, Sebastien J Hotte10, Claudio Jeldres11, Michael A S Jewett12, Wassim Kassouf13, Christian Kollmannsberger14, Luke T Lavallée7, Ranjena Maloni12, Francois Patenaude15, Frédéric Pouliot16, M Neil Reaume8, Robert Sabbagh11, Bobby Shayegan3, Alan So17, Denis Soulières18, Simon Tanguay13, Lori Wood19, Marco Bandini1,2. 1. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, QC, Canada. 2. Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, and Vita-Salute San Raffaele University, Milan, Italy. 3. Division of Urology, McMaster University, Hamilton, ON, Canada. 4. Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB, Canada. 5. Division of Medical Oncology/Hematology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada. 6. Division of Medical Oncology/Hematology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada. 7. Clinical Epidemiology Program and Division of Urology, The Ottawa Hospital Research Institute and University of Ottawa Ottawa, ON, Canada. 8. Division of Medical Oncology, The Ottawa Hospital Cancer Centre and the University of Ottawa, Ottawa, ON, Canada. 9. Section of Urology, University of Manitoba, Winnipeg, MB, Canada. 10. Juravinski Cancer and McMaster University, Hamilton, ON, Canada. 11. Centre hospitalier de l'Université de Sherbrooke, Sherbrooke, QC, Canada. 12. Departments of Surgery (Urology) and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. 13. Division of Urology, McGill University, Montreal, QC, Canada. 14. Division of Medical Oncology, British Columbia Cancer Agency-Vancouver Cancer Centre, and the University of British Columbia, Vancouver, BC, Canada. 15. Department of Medicine, Hematology Service and Department of Oncology, Sir Mortimer B. Davis Jewish General Hospital and McGill University, Montreal, QC, Canada. 16. Division of Urology, Department of Surgery, Université Laval, Quebec, QC, Canada. 17. Department of Urologic Sciences, The University of British Columbia, Vancouver, BC, Canada. 18. Division of Medical Oncology/Hematology Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada. 19. Department of Medicine and Urology, Dalhousie University, Halifax, NS, Canada.
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 non-metastatic 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.
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 non-metastatic 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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