Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors
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, I Davis, H Gurney, K Pittman, D Goldstein, P Mainwaring, J Knox, S Ades, T Cheng, S Hotte, Y-J Ko, M MacKenzie, S North, B Escudier, S Oudard, A Ravaud, A Caty, F Rolland, C Chevreau, B Duclos, S Negrier, V Grunwald, J Gschwend, P Albers, L Bergmann, J Beck, C Porta, S Bracarda, P Conte, E Bajetta, R Passalacqua, C Sternberg, F Boccardo, G Carteni, H Akaza, H Uemura, N Shinohara, N Tsuchiya, H Fujimoto, M Niwakawa, H Kanayama, M Eto, Y Sumiyoshi, T Tsukamoto, M Usami, A Terai, Y Hamamoto, M Maruoka, S Osanto, C Van Herpen, F Van Den Eertwegh, G Groenewegen, C Szczylik, J Pikiel, A Pluzanska, R Zdrojowy, E Calvo, F del Muro, M Climent, D Castellano, P Maroto, R Motzer, T Hutson, J Thompson, R Figlin, N Gabrail, L Appleman, D George, J Hamm, A Hussain, J Hajdenberg, N Vogelzang, T Logan, J Beck, K Rathmell, P Lara, A Dudek, U Vaishampayan, M Gordon, T Anderson, M Danso, W Berry, R Gersh, G Guzley, D Loesch, D Schlossman, D Smith, C Alemany, 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, I Davis, H Gurney, K Pittman, D Goldstein, P Mainwaring, J Knox, S Ades, T Cheng, S Hotte, Y-J Ko, M MacKenzie, S North, B Escudier, S Oudard, A Ravaud, A Caty, F Rolland, C Chevreau, B Duclos, S Negrier, V Grunwald, J Gschwend, P Albers, L Bergmann, J Beck, C Porta, S Bracarda, P Conte, E Bajetta, R Passalacqua, C Sternberg, F Boccardo, G Carteni, H Akaza, H Uemura, N Shinohara, N Tsuchiya, H Fujimoto, M Niwakawa, H Kanayama, M Eto, Y Sumiyoshi, T Tsukamoto, M Usami, A Terai, Y Hamamoto, M Maruoka, S Osanto, C Van Herpen, F Van Den Eertwegh, G Groenewegen, C Szczylik, J Pikiel, A Pluzanska, R Zdrojowy, E Calvo, F del Muro, M Climent, D Castellano, P Maroto, R Motzer, T Hutson, J Thompson, R Figlin, N Gabrail, L Appleman, D George, J Hamm, A Hussain, J Hajdenberg, N Vogelzang, T Logan, J Beck, K Rathmell, P Lara, A Dudek, U Vaishampayan, M Gordon, T Anderson, M Danso, W Berry, R Gersh, G Guzley, D Loesch, D Schlossman, D Smith, C Alemany
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.
Source: PubMed