Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors.

Abstract

BACKGROUND:

A phase 3 trial demonstrated superiority at interim analysis for everolimus over placebo in patients with metastatic renal cell carcinoma (mRCC) progressing on vascular endothelial growth factor receptor-tyrosine kinase inhibitors. Final results and analysis of prognostic factors are reported.

METHODS:

Patients with mRCC (N = 416) were randomized (2:1) to everolimus 10 mg/d (n = 277) or placebo (n = 139) plus best supportive care. Progression-free survival (PFS) and safety were assessed to the end of double-blind treatment. Mature overall survival (OS) data were analyzed, and prognostic factors for survival were investigated by multivariate analyses. A rank-preserving structural failure time model estimated the effect on OS, correcting for crossover from placebo to everolimus.

RESULTS:

The median PFS was 4.9 months (everolimus) versus 1.9 months (placebo) (hazard ratio [HR], 0.33; P < .001) by independent central review and 5.5 months (everolimus) versus 1.9 months (placebo) (HR, 0.32; P < .001) by investigators. Serious adverse events with everolimus, independent of causality, in ≥ 5% of patients included infections (all types, 10%), dyspnea (7%), and fatigue (5%). The median OS was 14.8 months (everolimus) versus 14.4 months (placebo) (HR, 0.87; P = .162), with 80% of patients in the placebo arm crossed over to everolimus. By the rank-preserving structural failure time model, the survival corrected for crossover was 1.9-fold longer (95% confidence interval, 0.5-8.5) with everolimus compared with placebo only. Independent prognostic factors for shorter OS in the study included low performance status, high corrected calcium, low hemoglobin, and prior sunitinib (P < .01).

CONCLUSIONS:

These results established the efficacy and safety of everolimus in patients with mRCC after progression on sunitinib and/or sorafenib.

• Authors: Robert J Motzer, Bernard Escudier, Stephane Oudard, Thomas E Hutson, Camillo Porta, Sergio Bracarda, Viktor Grünwald, John A Thompson, Robert A Figlin, Norbert Hollaender, Andrea Kay, Alain Ravaud, RECORD‐1 Study Group
• Journal: Cancer (Cancer) Vol. 116 Issue 18 Pg. 4256-65 (Sep 15 2010) ISSN: 0008-543X [Print] United States
• PMID: 20549832 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 American Cancer Society.

Chemical References

• Antineoplastic Agents
• Placebos
• Everolimus
• Sirolimus

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Renal Cell (drug therapy, mortality, pathology)
• Double-Blind Method
• Everolimus
• Humans
• Kidney Neoplasms (drug therapy, mortality, pathology)
• Middle Aged
• Neoplasm Metastasis
• Placebos
• Prognosis
• Retreatment
• Sirolimus (analogs & derivatives, therapeutic use)