Journal Article

Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma

Bensalah, Karim, Gross-Goupil, Marine, Aitchison, Michael, Ravaud, Alain, Rolland, Frederic, Timsit, Marc-Olivier, Beauval, Jean-Baptiste, Hubert, Jacques, Guy, Laurent, Colas, Sandra, Laguerre, Brigitte, Geoffrois, Lionnel, Cormier, Luc, Gravis, Gwenaelle, Bernhard, Jean-Christophe, Lang, Hervé, Lechevallier, Eric, Theodore, Christine, Méjean, Arnaud, Lebret, Thierry, Linassier, Claude, Chevreau, Christine, Beisland, Christian, Escudier, Bernard, Thiery-Vuillemin, Antoine, Patard, Jean-Jacques, Thezenas, Simon, Oudard, Stephane, Albiges, Laurence

2018

Overview

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. 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. 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. 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 .).

• Publisher: Massachusetts Medical Society
• Subject: Adult / Aged / Aged, 80 and over / Antineoplastic Agents - adverse effects / Antineoplastic Agents - therapeutic use / Carcinoma, Renal Cell - drug therapy / Carcinoma, Renal Cell - mortality / Carcinoma, Renal Cell - secondary / Carcinoma, Renal Cell - surgery / Clear cell-type renal cell carcinoma / Clinical trials / Combined Modality Therapy / Design / Female / Follow-Up Studies / Hospitals / Humans / Indoles - adverse effects / Indoles - therapeutic use / Inhibitor drugs / Kidney cancer / Kidney Neoplasms - drug therapy / Kidney Neoplasms - mortality / Kidney Neoplasms - pathology / Kidney Neoplasms - surgery / Life Sciences / Male / Medical prognosis / Metastases / Metastasis / Middle Aged / Neoplasm Staging / Nephrectomy / Nephrectomy - adverse effects / Oncology / Patient Selection / Postoperative Complications / Prognosis / Pyrroles - adverse effects / Pyrroles - therapeutic use / Risk Assessment / Sunitinib / Survival Analysis / Targeted cancer therapy / Urology / Vascular endothelial growth factor