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.
RCT Entities:
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: José Baselga; Mario Campone; Martine Piccart; Howard A Burris; Hope S Rugo; Tarek Sahmoud; Shinzaburo Noguchi; Michael Gnant; Kathleen I Pritchard; Fabienne Lebrun; J Thaddeus Beck; Yoshinori Ito; Denise Yardley; Ines Deleu; Alejandra Perez; Thomas Bachelot; Luc Vittori; Zhiying Xu; Pabak Mukhopadhyay; David Lebwohl; Gabriel N Hortobagyi Journal: N Engl J Med Date: 2011-12-07 Impact factor: 91.245
Authors: Lucia B Jilaveanu; Joshua Sznol; Saadia A Aziz; Dylan Duchen; Harriet M Kluger; Robert L Camp Journal: Hum Pathol Date: 2012-03-07 Impact factor: 3.466
Authors: Mas Jewett; A Finelli; C Kollmannsberger; L Wood; L Legere; J Basiuk; C Canil; D Heng; N Reaume; S Tanguay; M Atkins; G Bjarnason; J Dancey; M Evans; N Fleshner; M Haider; A Kapoor; R Uzzo; D Maskens; D Soulieres; G Yousef; N Basappa; N Bendali; P Black; N Blais; I Cagiannos; M Care; R Chow; H Chung; P Czaykowski; D Derosa; K Durrant; S Ellard; G Farquharson; C Filion-Brulotte; J Gingerich; L Godbout; R Grant; W Hamilton; W Kassouf; G Kurban; K Lane; Jb Lattouf; D Lau; M Leveridge; J McCarthy; R Moore; S North; P O'brien; E Pituskin; P Racine; R Rendon; A So; S Sridhar; K Stubbs; Z Su; L Taylor; T Udall; P Venner; W Vogel; S Yap; P Yau; M Cooper; N Giroux; D Miron; D Mosher; K Ross; J Willacy Journal: Can Urol Assoc J Date: 2012-02 Impact factor: 1.862
Authors: Xin Gao; Opeyemi Jegede; Connor Gray; Paul J Catalano; Jesse Novak; David J Kwiatkowski; Rana R McKay; Daniel J George; Toni K Choueiri; David F McDermott; Sabina Signoretti; Rupal S Bhatt Journal: Clin Genitourin Cancer Date: 2018-04-25 Impact factor: 2.872