Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.

Abstract

BACKGROUND:

Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.

METHODS:

We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression-free survival. Secondary efficacy end points were overall survival and objective response rate.

RESULTS:

Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005) but did not cross the significance boundary for the interim analysis. Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus.

CONCLUSIONS:

Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.).

• Authors: Toni K Choueiri, Bernard Escudier, Thomas Powles, Paul N Mainwaring, Brian I Rini, Frede Donskov, Hans Hammers, Thomas E Hutson, Jae-Lyun Lee, Katriina Peltola, Bruce J Roth, Georg A Bjarnason, Lajos Géczi, Bhumsuk Keam, Pablo Maroto, Daniel Y C Heng, Manuela Schmidinger, Philip W Kantoff, Anne Borgman-Hagey, Colin Hessel, Christian Scheffold, Gisela M Schwab, Nizar M Tannir, Robert J Motzer, METEOR Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 373 Issue 19 Pg. 1814-23 (Nov 05 2015) ISSN: 1533-4406 [Electronic] United States
• PMID: 26406150 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anilides
• Antineoplastic Agents
• Pyridines
• cabozantinib
• Everolimus
• Sirolimus

Topics

• Adult
• Aged
• Aged, 80 and over
• Anilides (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Carcinoma, Renal Cell (drug therapy, mortality)
• Disease-Free Survival
• Everolimus
• Female
• Humans
• Kidney Neoplasms (drug therapy, mortality)
• Male
• Middle Aged
• Pyridines (adverse effects, therapeutic use)
• Quality of Life
• Sirolimus (adverse effects, analogs & derivatives, therapeutic use)
• Survival Analysis