Robert J Motzer1, Bernard Escudier2, Saby George3, Hans J Hammers4, Sandhya Srinivas5, Scott S Tykodi6, Jeffrey A Sosman7, Elizabeth R Plimack8, Giuseppe Procopio9, David F McDermott10, Daniel Castellano11, Toni K Choueiri12, Frede Donskov13, Howard Gurney14, Stéphane Oudard15, Martin Richardet16, Katriina Peltola17, Ajjai S Alva18, Michael Carducci19, John Wagstaff20, Christine Chevreau21, Satoshi Fukasawa22, Yoshihiko Tomita23, Thomas C Gauler24, Christian K Kollmannsberger25, Fabio A Schutz26, James Larkin27, David Cella28, M Brent McHenry29, Shruti Shally Saggi30, Nizar M Tannir31. 1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 2. Department of Medical Oncology, Gustave Roussy, Villejuif, France. 3. Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York. 4. Division of Hematology and Oncology, UT Southwestern Kidney Cancer Program, Dallas, Texas. 5. Stanford Cancer Institute, Stanford University Medical Center, Stanford, California. 6. Department of Medicine, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington. 7. Department of Hematology/Oncology, Northwestern University Medical Center, Chicago, Illinois. 8. Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 9. Fondazione Istituto Nazionale Tumori, Milan, Italy. 10. Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts. 11. Oncologia Medica, Hospital Universitario 12 De Octubre, Madrid, Spain. 12. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 13. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 14. Department of Medical Oncology, Westmead Hospital and Macquarie University, Westmead, New South Wales, Australia. 15. Service de Cancérologie Médicale, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France. 16. Fundacion Richardet Longo, Instituto Oncologico de Cordoba, Cordoba, Argentina. 17. Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland. 18. Division of Hematology and Oncology, University of Michigan, Ann Arbor, Michigan. 19. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, Maryland. 20. South West Wales Cancer Institute and Swansea University College of Medicine, Swansea, United Kingdom. 21. Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France. 22. Prostate Center and Division of Urology, Chiba Cancer Center, Chiba, Japan. 23. Department of Urology, Department of Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 24. Department of Medicine, University Hospital Essen, University of Duisburg-Essen, Duisburg, Germany. 25. Division of Medical Oncology, BC Cancer-Vancouver Cancer Centre, Vancouver, British Columbia, Canada. 26. Beneficencia Portuguesa de São Paulo, São Paulo, Brazil. 27. Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom. 28. Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 29. Department of Biostatistics, Bristol Myers Squibb, Princeton, New Jersey. 30. Department of Clinical Trials, Bristol Myers Squibb, Princeton, New Jersey. 31. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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.
RCT Entities:
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.
Authors: Bérengère Salomé; John P Sfakianos; Daniel Ranti; Jorge Daza; Christine Bieber; Andrew Charap; Christian Hammer; Romain Banchereau; Adam M Farkas; Dan Fu Ruan; Sudeh Izadmehr; Daniel Geanon; Geoffrey Kelly; Ronaldo M de Real; Brian Lee; Kristin G Beaumont; Sanjana Shroff; Yuanshuo A Wang; Ying-Chih Wang; Tin Htwe Thin; Monica Garcia-Barros; Everardo Hegewisch-Solloa; Emily M Mace; Li Wang; Timothy O'Donnell; Diego Chowell; Ruben Fernandez-Rodriguez; Mihaela Skobe; Nicole Taylor; Seunghee Kim-Schulze; Robert P Sebra; Doug Palmer; Eleanor Clancy-Thompson; Scott Hammond; Alice O Kamphorst; Karl-Johan Malmberg; Emanuela Marcenaro; Pedro Romero; Rachel Brody; Mathias Viard; Yuko Yuki; Maureen Martin; Mary Carrington; Reza Mehrazin; Peter Wiklund; Ira Mellman; Sanjeev Mariathasan; Jun Zhu; Matthew D Galsky; Nina Bhardwaj; Amir Horowitz Journal: Cancer Cell Date: 2022-09-12 Impact factor: 38.585
Authors: Nizar M Tannir; Kyriakos P Papadopoulos; Deborah J Wong; Raid Aljumaily; Annie Hung; Manuel Afable; Jong Seok Kim; David Ferry; Alexandra Drakaki; Johanna Bendell; Aung Naing Journal: Int J Cancer Date: 2021-03-24 Impact factor: 7.396
Authors: Daniel M Geynisman; Jodi K Maranchie; Mark W Ball; Gennady Bratslavsky; Eric A Singer Journal: Urol Oncol Date: 2021-06-04 Impact factor: 2.954
Authors: Sara Elena Rebuzzi; Alessio Signori; Giuseppe Luigi Banna; Marco Maruzzo; Ugo De Giorgi; Paolo Pedrazzoli; Andrea Sbrana; Paolo Andrea Zucali; Cristina Masini; Emanuele Naglieri; Giuseppe Procopio; Sara Merler; Laura Tomasello; Lucia Fratino; Cinzia Baldessari; Riccardo Ricotta; Stefano Panni; Veronica Mollica; Maria Sorarù; Matteo Santoni; Alessio Cortellini; Veronica Prati; Hector Josè Soto Parra; Marco Stellato; Francesco Atzori; Sandro Pignata; Carlo Messina; Marco Messina; Franco Morelli; Giuseppe Prati; Franco Nolè; Francesca Vignani; Alessia Cavo; Giandomenico Roviello; Francesco Pierantoni; Chiara Casadei; Melissa Bersanelli; Silvia Chiellino; Federico Paolieri; Matteo Perrino; Matteo Brunelli; Roberto Iacovelli; Camillo Porta; Sebastiano Buti; Giuseppe Fornarini Journal: Ther Adv Med Oncol Date: 2021-05-18 Impact factor: 8.168