ASCO 2017: Outcomes based on age in the phase 3 METEOR trial of cabozantinib (cabo) vs everolimus (eve) in patients with advanced renal cell carcinoma (RCC)

Chicago, IL ( There has been much excitement over the past several years with regards to new second line therapies for patients with metastatic renal cell carcinoma (mRCC) demonstrating a survival benefit. In 2015, the phase III METEOR trial showed a significant improvement in progression-free survival (PFS; HR 0.58, 95%CI 0.45–0.75), overall survival (OS; HR 0.67, 95%CI 0.51–0.89), and objective response rate (ORR; 17% vs 3%; P < 0.0001) for cabozantinib compared with everolimus in patients with advanced RCC previously treated with VEGFR TKIs [1]. Given that the highest incidence rate for RCC is at ~75 years of age, the aim of the current study presented at today’s genitourinary cancer poster session at the 2017 ASCO annual meeting was to provide a post-hoc analysis of the METEOR trial stratified by three age categories.

There were 658 patients in the trial randomized 1:1 to receive 60 mg daily cabozantinib or 10 mg daily everolimus. The randomization was stratified by MSKCC risk group and the number of prior VEGFR TIKs received. The primary endpoints for the trial were PFS, OS and ORR, and for the subgroup analysis presented today, the age categories were <65 (60%), 65-74 (31%), and ≥75 years of age (10%). The ORR per independent radiology review for cabozantinib vs everolimus was 15% vs 5% for < 65 years old, 21% vs 2% for 65-74 years old, and 19% vs 0% for ≥75 years old. The HRs for PFS also favored cabozantinib for all age groups (< 65: HR 0.53, 95%CI 0.41–0.68; 65-74: HR 0.53, 95%CI 0.37–0.77; ≥75: HR 0.38, 95%CI 0.18–0.79). Furthermore, the HRs for OS also favored cabozantinib (<65; HR 0.72, 95%CI 0.54–0.95; 65-74: HR 0.66, 95%CI 0.44–0.99; ≥75 HR 0.57, 95%CI 0.28–1.14), although this was not significant in the oldest age group. Older patients more frequently had dose reductions, particularly in patients ≥75 years of age (cabozantinip – 85% vs everolimus – 36%). Grade 3 or 4 adverse events were generally consistent with the safety profiles in the overall population.

In conclusion, this post-hoc analysis of the METEOR phase III clinical trial demonstrated improved survival outcomes for cabozantinib compared to everolimus, irrespective of age. However, tolerability of cabozantinib was poorer in the older population, although dose reduction likely overcomes this reported intolerance.
Clinical trial: NCT01865747

Presented By: Frede Donskov, Aarhus University Hospital, Aarhus, Denmark

Co-Authors: Robert J. Motzer, Eric Voog, Elizabeth J. Hovey, Carsten Grüllich, Louise M. Nott, Katharine Ellen Cuff, Thierry Gil, Niels Viggo Jensen, Christine Chevreau, Sylvie Negrier, Reinhard Depenbusch, Lothar Bergmann, Izzy Cornelio, Anne Champsaur, Bernard J. Escudier, Sumanta K. Pal, Thomas Powles, Toni K. Choueiri

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA

1. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015 Nov 5;373(19):1814-1823.