Outcomes based on age in the phase III METEOR trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma.

Abstract

BACKGROUND:

Cabozantinib 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.

METHODS:

Efficacy and safety in METEOR were retrospectively analysed for three age subgroups: <65 (n = 394), 65-74 (n = 201) and ≥75 years (n = 63).

RESULTS:

PFS, 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.

CONCLUSIONS:

Cabozantinib 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.

• Authors: 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, Toni K Choueiri
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 126 Pg. 1-10 (02 2020) ISSN: 1879-0852 [Electronic] England
• PMID: 31887537 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Anilides
• Antineoplastic Agents
• Protein Kinase Inhibitors
• Pyridines
• cabozantinib
• Everolimus

Topics

• Adult
• Age Factors
• Aged
• Anilides (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Carcinoma, Renal Cell (drug therapy)
• Diarrhea (chemically induced)
• Everolimus (adverse effects, therapeutic use)
• Fatigue (chemically induced)
• Female
• Humans
• Hypertension (chemically induced)
• Kaplan-Meier Estimate
• Kidney Neoplasms (drug therapy)
• Male
• Middle Aged
• Outcome Assessment, Health Care (methods, statistics & numerical data)
• Proportional Hazards Models
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Pyridines (adverse effects, therapeutic use)
• Retrospective Studies