Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
Robert J Motzer, Bernard Escudier, David F McDermott, Saby George, Hans J Hammers, Sandhya Srinivas, Scott S Tykodi, Jeffrey A Sosman, Giuseppe Procopio, Elizabeth R Plimack, Daniel Castellano, Toni K Choueiri, Howard Gurney, Frede Donskov, Petri Bono, John Wagstaff, Thomas C Gauler, Takeshi Ueda, Yoshihiko Tomita, Fabio A Schutz, Christian Kollmannsberger, James Larkin, Alain Ravaud, Jason S Simon, Li-An Xu, Ian M Waxman, Padmanee Sharma, CheckMate 025 Investigators, E Korbenfeld, F S Palazzo, G Recondo, M Chacon, M E Richardet, M Susana, D Pook, G Toner, H Gurney, I Davis, K B Pittman, A Kavina, M Schmidinger, W Loidl, D Schallier, J-P Machiels, P Schoffski, S Rottey, C Dzik, F Schutz, F A Franke, C K Kollmannsberger, D Heng, J Knox, L Wood, N Basappa, P Zalewski, S Ghedira, W Miller, B Melichar, E Kubala, J Prausova, F Donskov, N V Jensen, P Geertsen, P Bono, A Ravaud, B Escudier, C Chevreau, F Rolland, G Gravis, J-M Tourani, L Geoffrois, S Oudard, A Heidenreich, F Imkamp, J Bedke, J Meiler, M Retz, P Goebell, S Pahernik, A Bamias, K Papazsis, J A McCaffrey, R McDermott, A Neumann, R Berger, V Neiman, A Santoro, C Sternberg, F Roila, G Procopio, M Maio, S Bracarda, U De Giorgi, F Hongo, G Kimura, H Kanayama, H Kitamura, H Kume, H Uemura, J Yonese, K Tanabe, K Tatsugami, M Eto, M Oya, M Saito, M Uemura, M Yao, N Shinohara, R Yamaguchi, S Fukasawa, T Kato, T Sugiyama, W Obara, D Heinrich, O Straume, C Szcylik, G Slomian, J Wojcik-Tomaszewska, P Tomczak, R Zdrojowy, C Volovat, D Lungulescu, I Sinescu, E Poddubskaya, P Karlov, V Matveev, C Suarez, D Castellano, J Puente, J A Arranz, J L Perez Gracia, X Garcia Del Muro, A Jellvert, U Harmenberg, J Wagstaff, M Gore, P Nathan, T Eisen, A Alva, A Amin, B Carthon, D McDermott, D Quinn, D Vaena, E Lam, E Plimack, F Millard, F Quddus, H Beltran, H Drabkin, H-J Hammers, J Brugarolas, J Clark, J Hainsworth, J Sarantopoulos, J Sosman, J T Beck, L Fong, M Fishman, M Harrison, N Dawson, P Sharma, R Figlin, R Motzer, S George, S Srinivas, S Tykodi, T Kuzel, T Logan, T Olencki, U Vaishampayan, W Voelzke, Robert J Motzer, Bernard Escudier, David F McDermott, Saby George, Hans J Hammers, Sandhya Srinivas, Scott S Tykodi, Jeffrey A Sosman, Giuseppe Procopio, Elizabeth R Plimack, Daniel Castellano, Toni K Choueiri, Howard Gurney, Frede Donskov, Petri Bono, John Wagstaff, Thomas C Gauler, Takeshi Ueda, Yoshihiko Tomita, Fabio A Schutz, Christian Kollmannsberger, James Larkin, Alain Ravaud, Jason S Simon, Li-An Xu, Ian M Waxman, Padmanee Sharma, CheckMate 025 Investigators, E Korbenfeld, F S Palazzo, G Recondo, M Chacon, M E Richardet, M Susana, D Pook, G Toner, H Gurney, I Davis, K B Pittman, A Kavina, M Schmidinger, W Loidl, D Schallier, J-P Machiels, P Schoffski, S Rottey, C Dzik, F Schutz, F A Franke, C K Kollmannsberger, D Heng, J Knox, L Wood, N Basappa, P Zalewski, S Ghedira, W Miller, B Melichar, E Kubala, J Prausova, F Donskov, N V Jensen, P Geertsen, P Bono, A Ravaud, B Escudier, C Chevreau, F Rolland, G Gravis, J-M Tourani, L Geoffrois, S Oudard, A Heidenreich, F Imkamp, J Bedke, J Meiler, M Retz, P Goebell, S Pahernik, A Bamias, K Papazsis, J A McCaffrey, R McDermott, A Neumann, R Berger, V Neiman, A Santoro, C Sternberg, F Roila, G Procopio, M Maio, S Bracarda, U De Giorgi, F Hongo, G Kimura, H Kanayama, H Kitamura, H Kume, H Uemura, J Yonese, K Tanabe, K Tatsugami, M Eto, M Oya, M Saito, M Uemura, M Yao, N Shinohara, R Yamaguchi, S Fukasawa, T Kato, T Sugiyama, W Obara, D Heinrich, O Straume, C Szcylik, G Slomian, J Wojcik-Tomaszewska, P Tomczak, R Zdrojowy, C Volovat, D Lungulescu, I Sinescu, E Poddubskaya, P Karlov, V Matveev, C Suarez, D Castellano, J Puente, J A Arranz, J L Perez Gracia, X Garcia Del Muro, A Jellvert, U Harmenberg, J Wagstaff, M Gore, P Nathan, T Eisen, A Alva, A Amin, B Carthon, D McDermott, D Quinn, D Vaena, E Lam, E Plimack, F Millard, F Quddus, H Beltran, H Drabkin, H-J Hammers, J Brugarolas, J Clark, J Hainsworth, J Sarantopoulos, J Sosman, J T Beck, L Fong, M Fishman, M Harrison, N Dawson, P Sharma, R Figlin, R Motzer, S George, S Srinivas, S Tykodi, T Kuzel, T Logan, T Olencki, U Vaishampayan, W Voelzke
Abstract
Background: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment.
Methods: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety.
Results: The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P≤0.0148). The objective response rate was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 [95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus; the most common event with nivolumab was fatigue (in 2% of the patients), and the most common event with everolimus was anemia (in 8%).
Conclusions: Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).
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Source: PubMed