Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors.
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.
Motzer
Robert J
RJ
Department of Medicine, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. motzerr@mskcc.org
Escudier
Bernard
B
Oudard
Stephane
S
Hutson
Thomas E
TE
Porta
Camillo
C
Bracarda
Sergio
S
Grünwald
Viktor
V
Thompson
John A
JA
Figlin
Robert A
RA
Hollaender
Norbert
N
Kay
Andrea
A
Ravaud
Alain
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004311:Double-Blind Method; D000068338:Everolimus; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010919:Placebos; D011379:Prognosis; D019233:Retreatment; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D010919:Placebos; D000068338:Everolimus; D020123:Sirolimus