Arnaud Méjean1, Alain Ravaud1, Simon Thezenas1, Sandra Colas1, Jean-Baptiste Beauval1, Karim Bensalah1, Lionnel Geoffrois1, Antoine Thiery-Vuillemin1, Luc Cormier1, Hervé Lang1, Laurent Guy1, Gwenaelle Gravis1, Frederic Rolland1, Claude Linassier1, Eric Lechevallier1, Christian Beisland1, Michael Aitchison1, Stephane Oudard1, Jean-Jacques Patard1, Christine Theodore1, Christine Chevreau1, Brigitte Laguerre1, Jacques Hubert1, Marine Gross-Goupil1, Jean-Christophe Bernhard1, Laurence Albiges1, Marc-Olivier Timsit1, Thierry Lebret1, Bernard Escudier1. 1. From the Departments of Urology (A.M., M.-O.T.) and Medical Oncology (S.O.), Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Descartes, and Paris Descartes Necker-Cochin Clinical Research Unit, AP-HP (S.C.), Paris, the Department of Medical Oncology, Bordeaux University Hospital (A.R.), the Department of Medical Oncology, Hôpital Saint André, Centre Hospitalier Universitaire (CHU) de Bordeaux (M.G.-G.), and the Department of Urology, CHU de Bordeaux and Université de Bordeaux (J.-C.B.), Bordeaux, Biometrics Unit, Cancer Institute of Montpellier, University of Montpellier, Montpellier (S.T.), the Department of Urology, CHU Rangueil (J.-B.B.), and the Department of Medical Oncology, Institut Universitaire du Cancer Toulouse-Oncopole (C.C.), Toulouse, the Department of Urology, University of Rennes (K.B.), and the Department of Medical Oncology, Centre Eugene Marquis (B.L.), Rennes, the Department of Medical Oncology, Institut de Cancerologie de Lorraine, Vandoeuvre lès Nancy (L. Geoffrois), the Department of Medical Oncology, CHU Besançon, Oncologie, and Université de Franche-Comte, INSERM Unité Mixte de Recherche (UMR) 1098, Structure Fédérative de Recherche Ingénierie et Biologie Cellulaire et Tissulaire, Besançon (A.T.-V.), the Department of Urology, CHU François Mitterrand, Dijon (L.C.), the Department of Urology, CHU Strasbourg, Translational Medicine Federation Strasbourg, Strasbourg (H.L.), the Department of Urology, Gabriel Montpied Hospital, and Clermont Auvergne University, Clermont-Ferrand (L. Guy), the Department of Medical Oncology, Centre de Recherche en Cancerologie de Marseille, INSERM UMR 1068, Centre National de la Recherche Scientifique UMR 7258 and Institut Paoli-Calmettes (G.G.), and the Department of Urology, Hôpital la Conception (E.L.), Aix Marseille Université, Marseille, the Department of Medical Oncology, Institut de Cancerologie de l'Ouest, Nantes (F.R.), the Department of Medical Oncology, CHU Bretonneau, and the Department of Medicine, Université François Rabelais, Tours (C.L.), the Department of Urology, Mont de Marsan General Hospital, Mont de Marsan (J.-J.P.), the Departments of Medical Oncology (C.T.) and Urology (T.L.), Hôpital Foch, Suresnes, the Department of Urology, Imagerie Adaptative Diagnostique et Interventionnelle INSERM Unité 1254, CHU de Nancy, Brabois (J.H.), the Department of Medical Oncology, Institut Gustave Roussy and Université Paris-Saclay, Villejuif (L.A., B.E.), and Université Versailles, St.-Quentin-en-Yvelines (T.L.) - all in France; the Department of Urology, Haukeland University Hospital (C.B.), and the Department of Clinical Medicine, University of Bergen (C.B.), Bergen, Norway; and the Department of Urology, Royal Free Hospital, London (M.A.).
Abstract
BACKGROUND:Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with confirmed metastatic clear-cell renal-cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receivesunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival. RESULTS: A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow-up was 50.9 months, with 326 deaths observed. The results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority, ≤1.20). The median overall survival was 18.4 months in the sunitinib-alone group and 13.9 months in the nephrectomy-sunitinib group. No significant differences in response rate or progression-free survival were observed. Adverse events were as anticipated in each group. CONCLUSIONS:Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal-cell carcinoma who were classified as having intermediate-risk or poor-risk disease. (Funded by Assistance Publique-Hôpitaux de Paris and others; CARMENA ClinicalTrials.gov number, NCT00930033 .).
RCT Entities:
BACKGROUND: Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with confirmed metastatic clear-cell renal-cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receive sunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival. RESULTS: A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow-up was 50.9 months, with 326 deaths observed. The results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority, ≤1.20). The median overall survival was 18.4 months in the sunitinib-alone group and 13.9 months in the nephrectomy-sunitinib group. No significant differences in response rate or progression-free survival were observed. Adverse events were as anticipated in each group. CONCLUSIONS:Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal-cell carcinoma who were classified as having intermediate-risk or poor-risk disease. (Funded by Assistance Publique-Hôpitaux de Paris and others; CARMENA ClinicalTrials.gov number, NCT00930033 .).
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Authors: Giuseppe Rosiello; Sophie Knipper; Carlotta Palumbo; Cristina Dzyuba-Negrean; Angela Pecoraro; Elio Mazzone; Francesco A Mistretta; Zhe Tian; Umberto Capitanio; Francesco Montorsi; Shahrokh F Shariat; Fred Saad; Alberto Briganti; Pierre I Karakiewicz Journal: Int Urol Nephrol Date: 2019-08-29 Impact factor: 2.370