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

Robert J. Motzer, Bernard Escudier, Saby George, Hans J. Hammers, Sandhya Srinivas, Scott S. Tykodi, Jeffrey A. Sosman, Elizabeth R. Plimack, Giuseppe Procopio, David F. McDermott, Daniel Castellano, Toni K. Choueiri, Frede Donskov, Howard Gurney, Stéphane Oudard, Martin Richardet, Katriina Peltola, Ajjai S. Alva, Michael Carducci, John WagstaffChristine Chevreau, Satoshi Fukasawa, Yoshihiko Tomita, Thomas C. Gauler, Christian K. Kollmannsberger, Fabio A. Schutz, James Larkin, David Cella, M. Brent McHenry, Shruti Shally Saggi, Nizar M. Tannir

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4156-4167
Number of pages12
JournalCancer
Volume126
Issue number18
DOIs
StatePublished - Sep 15 2020

Keywords

  • CheckMate 025
  • advanced renal cell carcinoma (aRCC)
  • everolimus
  • immune checkpoint inhibitor
  • nivolumab
  • previously treated

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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