• Frede Donskov, Robert J Motzer, Eric Voog, Elizabeth Hovey, Carsten Grüllich, Louise M Nott, Katharine Cuff, Thierry Gil, Niels Viggo Jensen, Christine Chevreau, Sylvie Negrier, Reinhard Depenbusch, Lothar Bergmann, Izzy Cornelio, Anne Champsaur, Bernard Escudier, Sumanta Pal, Thomas Powles, and Toni K Choueiri.
• Aarhus University Hospital, Aarhus, Denmark. Electronic address: Frede.Donskov@auh.rm.dk.
• Eur. J. Cancer. 2020 Feb 1; 126: 1-10.

BackgroundCabozantinib improved progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) compared with everolimus in patients with advanced renal cell carcinoma (RCC) after prior antiangiogenic therapy in the phase III METEOR trial (NCT01865747). Limited data are available on the use of targeted therapies in older patients with advanced RCC.MethodsEfficacy and safety in METEOR were retrospectively analysed for three age subgroups: <65 (n = 394), 65-74 (n = 201) and ≥75 years (n = 63).ResultsPFS, OS and ORR were improved with cabozantinib compared with everolimus in all age subgroups. The PFS hazard ratios (HRs) were 0.53 (95% confidence interval [CI]: 0.41-0.68), 0.53 (95% CI: 0.37-0.77) and 0.38 (95% CI: 0.18-0.79) for <65, 65-74 and ≥75 years, respectively, and the OS HRs were 0.72 (95% CI: 0.54-0.95), 0.66 (95% CI: 0.44-0.99) and 0.57 (95% CI: 0.28-1.14). The ORR for cabozantinib versus everolimus was 15% vs 5%, 21% vs 2% and 19% vs 0%, respectively. No significant differences were observed in PFS or OS with age as a categorical or continuous variable. Grade III/IV adverse events (AEs) were generally consistent across subgroups, although fatigue, hypertension and hyponatraemia occurred more frequently in older patients treated with cabozantinib. Dose reductions to manage AEs were more frequent in patients receiving cabozantinib than in those receiving everolimus. Dose reductions and treatment discontinuation due to AEs were more frequent in older patients in both treatment groups.ConclusionsCabozantinib improved PFS, OS and ORR compared with everolimus in previously treated patients with advanced RCC, irrespective of age group, supporting use in all age categories. Proactive dose modification and supportive care may help to mitigate AEs in older patients while maintaining efficacy.Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

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