Phase 3 trial of everolimus for metastatic renal cell carcinoma: Final results and analysis of prognostic factors Journal Article


Authors: Motzer, R. J.; Escudier, B.; Oudard, S.; Hutson, T. E.; Porta, C.; Bracarda, S.; Grünwald, V.; Thompson, J. A.; Figlin, R. A.; Hollaender, N.; Kay, A.; Ravaud, A.
Article Title: 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. © 2010 American Cancer Society.
Keywords: adult; controlled study; aged; aged, 80 and over; middle aged; major clinical study; overall survival; clinical trial; fatigue; sorafenib; sunitinib; diarrhea; drug safety; side effect; antineoplastic agents; anorexia; progression free survival; controlled clinical trial; infection; neutrophil count; nausea; randomized controlled trial; stomatitis; vomiting; creatinine blood level; hemoglobin blood level; kidney carcinoma; kidney neoplasms; alanine aminotransferase blood level; aspartate aminotransferase blood level; asthenia; coughing; dyspnea; fever; pneumonia; pruritus; rash; carcinoma, renal cell; prognostic factors; neoplasm metastasis; peripheral edema; thrombocyte count; glucose blood level; cholesterol blood level; triacylglycerol blood level; headache; phase 3 clinical trial; double blind procedure; double-blind method; dry skin; epistaxis; bilirubin blood level; everolimus; sirolimus; retreatment; lymphocyte count; placebos; dysgeusia; rad001; metastatic renal cell carcinoma; phase 3; phosphate blood level
Journal Title: Cancer
Volume: 116
Issue: 18
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2010-09-15
Start Page: 4256
End Page: 4265
Language: English
DOI: 10.1002/cncr.25219
PUBMED: 20549832
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 20" - "Export Date: 20 April 2011" - "CODEN: CANCA" - "Source: Scopus"
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  1. Robert Motzer
    769 Motzer