TY - JOUR
T1 - Efficacy of everolimus in advanced renal cell carcinoma
T2 - a double-blind, randomised, placebo-controlled phase III trial
AU - Motzer, Robert J.
AU - Escudier, Bernard
AU - Oudard, Stéphane
AU - Hutson, Thomas E.
AU - Porta, Camillo
AU - Bracarda, Sergio
AU - Grünwald, Viktor
AU - Thompson, John A.
AU - Figlin, Robert A.
AU - Hollaender, Norbert
AU - Urbanowitz, Gladys
AU - Berg, William J.
AU - Kay, Andrea
AU - Lebwohl, David
AU - Ravaud, Alain
PY - 2008
Y1 - 2008
N2 - Background: Everolimus (RAD001) is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), a therapeutic target for metastatic renal cell carcinoma. We did a phase III, randomised, double-blind, placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy. Methods: Patients with metastatic renal cell carcinoma which had progressed on sunitinib, sorafenib, or both, were randomly assigned in a two to one ratio to receive everolimus 10 mg once daily (n=272) or placebo (n=138), in conjunction with best supportive care. Randomisation was done centrally via an interactive voice response system using a validated computer system, and was stratified by Memorial Sloan-Kettering Cancer Center prognostic score and previous anticancer therapy, with a permuted block size of six. The primary endpoint was progression-free survival, assessed via a blinded, independent central review. The study was designed to be terminated after 290 events of progression. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00410124. Findings: All randomised patients were included in efficacy analyses. The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed (101 [37%] events in the everolimus group, 90 [65%] in the placebo group; hazard ratio 0·30, 95% CI 0·22-0·40, p
AB - Background: Everolimus (RAD001) is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), a therapeutic target for metastatic renal cell carcinoma. We did a phase III, randomised, double-blind, placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy. Methods: Patients with metastatic renal cell carcinoma which had progressed on sunitinib, sorafenib, or both, were randomly assigned in a two to one ratio to receive everolimus 10 mg once daily (n=272) or placebo (n=138), in conjunction with best supportive care. Randomisation was done centrally via an interactive voice response system using a validated computer system, and was stratified by Memorial Sloan-Kettering Cancer Center prognostic score and previous anticancer therapy, with a permuted block size of six. The primary endpoint was progression-free survival, assessed via a blinded, independent central review. The study was designed to be terminated after 290 events of progression. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00410124. Findings: All randomised patients were included in efficacy analyses. The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed (101 [37%] events in the everolimus group, 90 [65%] in the placebo group; hazard ratio 0·30, 95% CI 0·22-0·40, p
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U2 - 10.1016/S0140-6736(08)61039-9
DO - 10.1016/S0140-6736(08)61039-9
M3 - Article
C2 - 18653228
AN - SCOPUS:48649107474
VL - 372
SP - 449
EP - 456
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 9637
ER -