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Motzer RJ , Escudier B , George S , Hammers HJ , Srinivas S , Tykodi SS , Sosman JA , Plimack ER , Procopio G , McDermott DF , Castellano D , Choueiri TK , Donskov F , Gurney H , Oudard S , Richardet M , Peltola K , Alva AS , Carducci M , Wagstaff J , Chevreau C , Fukasawa S , Tomita Y , Gauler TC , Kollmannsberger CK , Schutz FA , Larkin J , Cella D , McHenry MB , Saggi SS , Tannir NM
Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial
Cancer. 2020 Jul 16;126(18) :4156-4167
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Abstract
BACKGROUND: CheckMate 025 has shown superior efficacy for nivolumab over everolimus in patients with advanced renal cell carcinoma (aRCC) along with improved safety and tolerability. This analysis assesses the long-term clinical benefits of nivolumab versus everolimus. METHODS: The randomized, open-label, phase 3 CheckMate 025 trial (NCT01668784) included patients with clear cell aRCC previously treated with 1 or 2 antiangiogenic regimens. Patients were randomized to nivolumab (3 mg/kg every 2 weeks) or everolimus (10 mg once a day) until progression or unacceptable toxicity. The primary endpoint was overall survival (OS). The secondary endpoints were the confirmed objective response rate (ORR), progression-free survival (PFS), safety, and health-related quality of life (HRQOL). RESULTS: Eight hundred twenty-one patients were randomized to nivolumab (n = 410) or everolimus (n = 411); 803 patients were treated (406 with nivolumab and 397 with everolimus). With a minimum follow-up of 64 months (median, 72 months), nivolumab maintained an OS benefit in comparison with everolimus (median, 25.8 months [95% CI, 22.2-29.8 months] vs 19.7 months [95% CI, 17.6-22.1 months]; hazard ratio [HR], 0.73; 95% CI, 0.62-0.85) with 5-year OS probabilities of 26% and 18%, respectively. ORR was higher with nivolumab (94 of 410 [23%] vs 17 of 411 [4%]; P < .001). PFS also favored nivolumab (HR, 0.84; 95% CI, 0.72-0.99; P = .0331). The most common treatment-related adverse events of any grade were fatigue (34.7%) and pruritus (15.5%) with nivolumab and fatigue (34.5%) and stomatitis (29.5%) with everolimus. HRQOL improved from baseline with nivolumab but remained the same or deteriorated with everolimus. CONCLUSIONS: The superior efficacy of nivolumab over everolimus is maintained after extended follow-up with no new safety signals, and this supports the long-term benefits of nivolumab monotherapy in patients with previously treated aRCC. LAY SUMMARY: CheckMate 025 compared the effects of nivolumab (a novel immunotherapy) with those of everolimus (an older standard-of-care therapy) for the treatment of advanced kidney cancer in patients who had progressed on antiangiogenic therapy. After 5 years of study, nivolumab continues to be better than everolimus in extending the lives of patients, providing a long-lasting response to treatment, and improving quality of life with a manageable safety profile. The results demonstrate that the clinical benefits of nivolumab versus everolimus in previously treated patients with advanced kidney cancer continue in the long term.
Notes
1097-0142 Motzer, Robert J Orcid: 0000-0001-6925-2327 Escudier, Bernard George, Saby Hammers, Hans J Srinivas, Sandhya Tykodi, Scott S Sosman, Jeffrey A Plimack, Elizabeth R Procopio, Giuseppe Orcid: 0000-0002-2498-402x McDermott, David F Castellano, Daniel Choueiri, Toni K Orcid: 0000-0002-9201-3217 Donskov, Frede Gurney, Howard Oudard, Stéphane Richardet, Martin Peltola, Katriina Alva, Ajjai S Carducci, Michael Wagstaff, John Orcid: 0000-0002-1140-5981 Chevreau, Christine Orcid: 0000-0001-9866-913x Fukasawa, Satoshi Tomita, Yoshihiko Gauler, Thomas C Kollmannsberger, Christian K Schutz, Fabio A Larkin, James Cella, David McHenry, M Brent Saggi, Shruti Shally Tannir, Nizar M Bristol-Myers Squibb and ONO Pharmaceutical Company Ltd/ P30 CA016672/NH/NIH HHS/United States Journal Article United States Cancer. 2020 Jul 16. doi: 10.1002/cncr.33033.