Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma
Toni K Choueiri, Bernard Escudier, Thomas Powles, Paul N Mainwaring, Brian I Rini, Frede Donskov, Hans Hammers, Thomas E Hutson, Jae-Lyun Lee, Katriina Peltola, Bruce J Roth, Georg A Bjarnason, Lajos Géczi, Bhumsuk Keam, Pablo Maroto, Daniel Y C Heng, Manuela Schmidinger, Philip W Kantoff, Anne Borgman-Hagey, Colin Hessel, Christian Scheffold, Gisela M Schwab, Nizar M Tannir, Robert J Motzer, METEOR Investigators, H Tan, E Hovey, P Mainwaring, C Steer, G Marx, P deSouza, I Davis, S Begbie, L Nott, D Pook, K Cuff, R Epstein, H Gurney, M Schmidinger, W Loidl, M De Santis, T Gil, W Wynendaele, W Demey, P Schöffski, J Knox, D Soulieres, P Czaykowski, N Basappa, C Kollmannsberger, G Bjarnason, L Wood, P Zalewski, S Hotte, D Heng, E Winquist, P Salman, O Aren Frontera, J Katolicka, B Melichar, N Jensen, P Geertsen, F Donskov, K Peltola, B Escudier, G Gravis, F Joly, C Chevreau, S Oudard, B Laguerre, F Rolland, E Voog, S Negrier, T Maurina, M Gross Goupil, M Staehler, D Pfister, M Rink, V Gruenwald, M Retz, M Wirth, W Schultze-Seemann, R Depenbusch, T Schnöller, L Bergmann, C Gruellich, T Csoszi, L Geczi, J McCaffrey, R McDermott, C Sternberg, P Passalacqua, U De Giorgi, R Sabbatini, F Boccardo, F Carrozza, F Roila, D Santini, S Bracarda, J van Thienen, M Aarts, S Osanto, P Tomczak, J Pikiel, M Wojtukiewicz, C Szczylik, N Sousa, J Passos Coelho, L Costa, S Cheporov, E Kopyltsov, D Nosov, I Mincik, J Mikulas, S Rha, B Keam, J Lee, S Park, E Grande, I Chirivella, X Garcia del Muro Solans, C Suarez, I Duran, D Castellano, J Garcia Donas, J Perez Gracia, A Martinez, M Saez Medina, P Maroto, E Esteban Gonzalez, U Harmenberg, M Thomasson, R Blom, C Lin, Y Chang, Y Ou, A Sevinc, F Dane, E Gokmen, R Yildiz, R Hawkins, S Hussain, J Larkin, P Nathan, E Porfiri, J Malik, A MacDonald, T Powles, S Chowdhury, H Glen, R Motzer, T Choueiri, D Geynisman, H Kluger, L Appleman, D Shaffer, M Fishman, J Hainsworth, G Sonpavde, H Drabkin, H Hammers, D George, J Merchan, A Hussain, A Koletsky, W Hanna, M Troner, U Vaishampayan, B Costello, T Olencki, D Vaena, B Redman, B Rini, W Stadler, B Roth, N Tannir, T Kuzel, J Wright, T Hutson, P Van Veldhuizen, S Richey, G Doshi, J Sarantopoulos, C Ryan, W Samlowski, S Tykodi, S Pal, N Agarwal, F Kabbinavar, R Figlin, T Ho, B Wong, P Singh, T Kolevska, J Randall, Toni K Choueiri, Bernard Escudier, Thomas Powles, Paul N Mainwaring, Brian I Rini, Frede Donskov, Hans Hammers, Thomas E Hutson, Jae-Lyun Lee, Katriina Peltola, Bruce J Roth, Georg A Bjarnason, Lajos Géczi, Bhumsuk Keam, Pablo Maroto, Daniel Y C Heng, Manuela Schmidinger, Philip W Kantoff, Anne Borgman-Hagey, Colin Hessel, Christian Scheffold, Gisela M Schwab, Nizar M Tannir, Robert J Motzer, METEOR Investigators, H Tan, E Hovey, P Mainwaring, C Steer, G Marx, P deSouza, I Davis, S Begbie, L Nott, D Pook, K Cuff, R Epstein, H Gurney, M Schmidinger, W Loidl, M De Santis, T Gil, W Wynendaele, W Demey, P Schöffski, J Knox, D Soulieres, P Czaykowski, N Basappa, C Kollmannsberger, G Bjarnason, L Wood, P Zalewski, S Hotte, D Heng, E Winquist, P Salman, O Aren Frontera, J Katolicka, B Melichar, N Jensen, P Geertsen, F Donskov, K Peltola, B Escudier, G Gravis, F Joly, C Chevreau, S Oudard, B Laguerre, F Rolland, E Voog, S Negrier, T Maurina, M Gross Goupil, M Staehler, D Pfister, M Rink, V Gruenwald, M Retz, M Wirth, W Schultze-Seemann, R Depenbusch, T Schnöller, L Bergmann, C Gruellich, T Csoszi, L Geczi, J McCaffrey, R McDermott, C Sternberg, P Passalacqua, U De Giorgi, R Sabbatini, F Boccardo, F Carrozza, F Roila, D Santini, S Bracarda, J van Thienen, M Aarts, S Osanto, P Tomczak, J Pikiel, M Wojtukiewicz, C Szczylik, N Sousa, J Passos Coelho, L Costa, S Cheporov, E Kopyltsov, D Nosov, I Mincik, J Mikulas, S Rha, B Keam, J Lee, S Park, E Grande, I Chirivella, X Garcia del Muro Solans, C Suarez, I Duran, D Castellano, J Garcia Donas, J Perez Gracia, A Martinez, M Saez Medina, P Maroto, E Esteban Gonzalez, U Harmenberg, M Thomasson, R Blom, C Lin, Y Chang, Y Ou, A Sevinc, F Dane, E Gokmen, R Yildiz, R Hawkins, S Hussain, J Larkin, P Nathan, E Porfiri, J Malik, A MacDonald, T Powles, S Chowdhury, H Glen, R Motzer, T Choueiri, D Geynisman, H Kluger, L Appleman, D Shaffer, M Fishman, J Hainsworth, G Sonpavde, H Drabkin, H Hammers, D George, J Merchan, A Hussain, A Koletsky, W Hanna, M Troner, U Vaishampayan, B Costello, T Olencki, D Vaena, B Redman, B Rini, W Stadler, B Roth, N Tannir, T Kuzel, J Wright, T Hutson, P Van Veldhuizen, S Richey, G Doshi, J Sarantopoulos, C Ryan, W Samlowski, S Tykodi, S Pal, N Agarwal, F Kabbinavar, R Figlin, T Ho, B Wong, P Singh, T Kolevska, J Randall
Abstract
Background: Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.
Methods: We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression-free survival. Secondary efficacy end points were overall survival and objective response rate.
Results: Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005) but did not cross the significance boundary for the interim analysis. Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus.
Conclusions: Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.).
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Source: PubMed