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 language | English (US) |
---|---|
Pages (from-to) | 4156-4167 |
Number of pages | 12 |
Journal | Cancer |
Volume | 126 |
Issue number | 18 |
DOIs | |
State | Published - 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
MD Anderson CCSG core facilities
- Clinical Trials Office
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In: Cancer, Vol. 126, No. 18, 15.09.2020, p. 4156-4167.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Nivolumab versus everolimus in patients with advanced renal cell carcinoma
T2 - Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial
AU - Motzer, Robert J.
AU - Escudier, Bernard
AU - George, Saby
AU - Hammers, Hans J.
AU - Srinivas, Sandhya
AU - Tykodi, Scott S.
AU - Sosman, Jeffrey A.
AU - Plimack, Elizabeth R.
AU - Procopio, Giuseppe
AU - McDermott, David F.
AU - Castellano, Daniel
AU - Choueiri, Toni K.
AU - Donskov, Frede
AU - Gurney, Howard
AU - Oudard, Stéphane
AU - Richardet, Martin
AU - Peltola, Katriina
AU - Alva, Ajjai S.
AU - Carducci, Michael
AU - Wagstaff, John
AU - Chevreau, Christine
AU - Fukasawa, Satoshi
AU - Tomita, Yoshihiko
AU - Gauler, Thomas C.
AU - Kollmannsberger, Christian K.
AU - Schutz, Fabio A.
AU - Larkin, James
AU - Cella, David
AU - McHenry, M. Brent
AU - Saggi, Shruti Shally
AU - Tannir, Nizar M.
N1 - Funding Information: This study was funded by Bristol‐Myers Squibb Company (BMS) and ONO Pharmaceutical Company, Ltd. The funders contributed to the study design, data analysis, and data interpretation in collaboration with the authors. The funders had no role in data collection. Financial support for editorial and writing assistance was provided by the funders. A data confidentiality agreement was in place between BMS and the investigators. All authors vouch for the completeness and accuracy of the data and analyses and for the adherence of the trial to the protocol. All authors had full access to all of the data included in the study, and all authors contributed to drafting the manuscript and provided final approval to submit the manuscript. The corresponding author had full access to all of the data and the final responsibility to submit the manuscript for publication. Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by the Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). The University of Texas MD Anderson Cancer Center is supported by the National Institutes of Health (grant P30 CA016672). Funding Information: We thank the patients and their families as well as the investigators and participating clinical study teams for making this study possible. We also thank Elmer Berghorn for his contributions to the study; Dako (an Agilent Technologies, Inc, company) for collaborative development of the PD‐L1 IHC 28‐8 pharmDx assay; and Bristol‐Myers Squibb Company (Princeton, New Jersey) and ONO Pharmaceutical Company, Ltd (Osaka, Japan). Professional medical writing and editorial assistance was provided by Jenny Reinhold, PharmD (Parexel), and was funded by Bristol‐Myers Squibb Company. Funding Information: Robert J. Motzer reports consulting or advisory roles with Eisai, Exelixis, Genentech/Roche, Lilly Oncology, Merck, Novartis, and Pfizer and research funding from Bristol‐Myers Squibb Company (BMS), Eisai, Exelixis, Novartis, and Pfizer, and travel/accomodations/expenses from BMS. Bernard Escudier reports honoraria from BMS, Ipsen, EUSA Pharma, Novartis, Pfizer, and Roche/Genentech. Saby George reports consulting or advisory roles with BMS, Novartis, Bayer, Pfizer, Exelixis, AstraZeneca, Janssen Oncology, Corvus Pharmaceuticals, Eisai, Genentech/Roche, EMD Serono, Seattle Genetics/Astellas, and Sanofi and research funding from Pfizer (institution), Acceleron Pharma (institution), Corvus Pharmaceuticals (institution), Merck (institution), Agensys (institution), Immunomedics (institution), Calithera Biosciences (institution), Novartis (institution), BMS (institution), Eisai (institution), Seattle Genetics/Astellas (institution), and Bayer (institution). Hans J. Hammers reports consulting or advisory roles with Corvus Pharmaceuticals, Merck, Surface Oncology, Armo Biosciences, Novartis, BMS, Pfizer, and Exelixis; and research funding from BMS and Merck. Sandhya Srinivas reports research funding from BMS. Scott S. Tykodi reports consulting or advisory roles with BMS, Calithera Biosciences, and Prometheus Laboratories and research funding from BMS (institution), Calithera Biosciences (institution), Merck (institution), Nektar Therapeutics (institution), Peloton Therapeutics (institution), Jounce Therapeutics (institution), Pfizer (institution), Genentech (institution), Prometheus Laboratories (institution), Argos Therapeutics (institution), Clinigen (institution), and Exelixis (institution); in addition, Tykodi has a provisional patent application pending. Jeffrey A. Sosman reports honoraria from Array, Genentech, Merck, and Novartis; personal fees from BMS, Merck, and Incyte; consulting or advisory roles with Array, Genentech, Merck, and Novartis; and research funding from BMS. Elizabeth R. Plimack reports consulting or advisory roles with BMS, AstraZeneca, Genentech/Roche, Merck, Novartis, Pfizer, Eli Lilly, Inovio, Clovis, Horizon Pharma, Exelixis, Incyte, McKesson, Janssen, Flatiron Health, Infinity Pharma, and Seattle Genetics; fees for the development of educational presentations from BMS, Merck, Roche, and Novartis; research funding from Acceleron (institution), Astellas (institution), AstraZeneca (institution), BMS (institution), GlaxoSmithKline (institution), Eli Lilly (institution), Merck (institution), Peloton Therapeutics (institution), and Pfizer (institution); a US patent pending (14/588,503 [filed January 2, 2015]); and honoraria for continuing medical education certified presentations from the American Urological Association, Clinical Care Options, Fox Chase Cancer Center, Georgetown, the American Society of Clinical Oncology, Medscape, Mt Sinai Icahn School of Medicine, the National Comprehensive Cancer Network, Omniprex, OncLive, PER, prIME Oncology, Research to Practice, Spire Learning, the University of Pennsylvania, Thomas Jefferson University, and the University of Michigan. Giuseppe Procopio reports consulting or advisory roles with AstraZeneca, Astellas, BMS, Ipsen, Janssen, MSD, Novartis, and Pfizer. David F. McDermott reports consulting or advisory roles with Alkermes, Array BioPharma, BMS, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Merck, Novartis, and Pfizer; research funding from Prometheus Laboratories (institution); and grants from BMS, Pfizer, Genentech, Merck, Alkermes, Exelixis, and X4 Pharma. Daniel Castellano reports consulting or advisory roles with Pfizer, Janssen, Astellas, Roche, Lilly, Ipsen, MSD, AstraZeneca, Bayer, BMS, and Pierre Fabre. Toni K. Choueiri reports research funding (institutional and personal) from AstraZeneca, Alexion, Bayer, BMS/ER Squibb and Sons LLC, Cerulean, Eisai, EMD Serono, Foundation Medicine, Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, F. Hoffmann–La Roche, GlaxoSmithKline, Lilly, Merck, Novartis, Peloton Therapeutics, Pfizer, Prometheus Laboratories, Corvus Pharmaceuticals, Calithera Biosciences, Analysis Group, Sanofi‐Aventis, and Takeda; honoraria from AstraZeneca, Alexion, Sanofi‐Aventis, Bayer, BMS/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine, Exelixis, Genentech, Roche, Roche Products Limited, F. Hoffmann–La Roche, GlaxoSmithKline, Merck, Novartis, Peloton Therapeutics, Pfizer, EMD Serono, Prometheus Laboratories, Corvus Pharmaceuticals, Ipsen, UpToDate, Analysis Group, the National Comprehensive Cancer Network, Michael J. Hennessy Associates (a Healthcare Communications Company with several brands such as OncLive, PeerView, and PER), L‐Path, , Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, the American Society of Medical Oncology, , , Heron Therapeutics, and Lilly; consulting or advisory roles with AstraZeneca, Alexion, Sanofi‐Aventis, Bayer, BMS/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine, Exelixis, Genentech, Heron Therapeutics, Lilly, Roche, GlaxoSmithKline, Merck, Novartis, Peloton Therapeutics, Pfizer, EMD Serono, Prometheus Laboratories, Corvus Pharmaceuticals, Ipsen, UpToDate, the National Comprehensive Cancer Network, and Analysis Group; and international patent applications (PCT/US2018/12209 [filed January 3, 2018] and PCT/US2018/058430 [filed October 31, 2018]). In addition, Dr. Choueiri reports stock ownership in Pionyr and Tempest and travel/accommodations/expenses in relation to consulting, advisory roles, and clinical trials; medical writing and editorial assistance support may have been funded by communication companies funded by pharmaceutical companies; Choueiri's institution (the Dana‐Farber Cancer Institute) may have received additional independent funding from drug companies or/and royalties potentially involved in research around the subject matter; and Choueiri sits on the National Comprehensive Cancer Network's kidney panel. Frede Donskov reports research funding from Ipsen (institution), Pfizer (institution), and BMS (institution). Howard Gurney reports consulting or advisory roles with Astellas, BMS, Ipsen, Novartis, Pfizer, Roche, MSD, and AstraZeneca. Stéphane Oudard reports honoraria from BMS, Pfizer, Novartis, Bayer, Merck, and Ipsen. Katriina Peltola reports advisory roles with BMS, Pfizer, MSD, Ipsen, Varian Medical, and Orion Pharma; lecture fees from BMS and Roche; and stock ownership in Faron Pharmaceuticals. Ajjai S. Alva reports research funding from BMS (institution), Merck (institution), AstraZeneca (institution), Arcus Biosciences (institution), Prometheus Laboratories (institution), Celgene (institution), Janssen (institution), Astellas/Seattle Genetics (institution), the American Society of Clinical Oncology (institution), and the National Cancer Institute/Experimental Therapeutics Clinical Trials Network (institution). Michael Carducci reports consulting or advisory roles with AstraZeneca, Merck, Astellas, and Medivation. John Wagstaff reports honoraria from Roche, BMS, Pfizer, Novartis, and MSD; consulting or advisory roles with Roche, BMS, Pfizer, Novartis, and MSD; involvement in speaker bureaus for Roche, BMS, Pfizer, Novartis, and MSD; personal fees from Roche, BMS, Pfizer, Novartis, and MSD; and travel/accommodations/expenses from BMS and MSD. Christine Chevreau reports consulting or advisory roles with BMS, Pfizer, Novartis, and Ipsen. Yoshihiko Tomita reports grants and personal fees from ONO Pharmaceutical Company, Ltd, and Astellas; personal fees from BMS and Pfizer; and grants from Takeda. Thomas C. Gauler reports stock or other ownership in Bayer; personal fees from Pfizer, AstraZeneca, and Sanofi‐Aventis; honoraria from BMS, Eisai, Ipsen, Merck Serono, MSD, Novartis, and Roche; consulting or advisory roles with BMS, Eisai, Ipsen, Merck Serono, MSD, and Novartis; and travel/accommodations/expenses from BMS, Ipsen, Merck Serono, MSD, and Novartis. Christian K. Kollmannsberger reports advisory board and lecture fees from Pfizer, Ipsen, Eisai, and BMS; and advisory board fees from Janssen, Astellas, Roche, and Merck. Fabio A. Schutz reports personal fees from BMS, MerckSharpeDohme, Janssen, Astellas, Roche, and Bayer. James Larkin reports honoraria from BMS, MSD, Pfizer, Novartis, Eisai, GlaxoSmithKline, Roche, Kymab, Secarna, Pierre Fabre, and EUSA Pharma; consulting or advisory roles with Achilles Therapeutics, AstraZeneca, Boston Biomedical, BMS, Ipsen, Imugene, MSD, Pfizer, Novartis, Eisai, GlaxoSmithKline, Roche, Incyte, Merck Serono, iOnctura, Kymab, Nektar, Secarna, Pierre Fabre, Vitaccess, Covance, Immunocore, and EUSA Pharma; and research funding from Achilles Therapeutics, Aveo, Pharmacyclics, BMS, MSD, Nektar, Pfizer, Roche/Genentech, Immunocore, and Novartis. David Cella reports grants and personal fees from BMS, AbbVie, Astellas, Novartis, and Pfizer; and grants from Bayer, Clovis, and GSK. M. Brent McHenry reports employment by BMS and stock or other ownership in BMS. Shruti Shally Saggi reports employment by BMS. Nizar M. Tannir reports grants from BMS, Nektar Therapeutics, Calithera Bioscience, Takeda, Arrowhead Pharmaceuticals, and Epizyme; grants and personal fees from Exelixis and Nektar Therapeutics; and personal fees from BMS, Pfizer, Lilly Oncology, Neolukin Therapeutics, Eisai, Novartis, Oncorena, ONO Pharmaceutical Company Ltd., Surface Oncology, and Ipsen. The other authors made no disclosures. Kidney Cancer Journal New England Journal of Medicine Lancet Oncology Publisher Copyright: © 2020 American Cancer Society
PY - 2020/9/15
Y1 - 2020/9/15
N2 - 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.
AB - 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.
KW - CheckMate 025
KW - advanced renal cell carcinoma (aRCC)
KW - everolimus
KW - immune checkpoint inhibitor
KW - nivolumab
KW - previously treated
UR - http://www.scopus.com/inward/record.url?scp=85088021619&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088021619&partnerID=8YFLogxK
U2 - 10.1002/cncr.33033
DO - 10.1002/cncr.33033
M3 - Article
C2 - 32673417
AN - SCOPUS:85088021619
SN - 0008-543X
VL - 126
SP - 4156
EP - 4167
JO - Cancer
JF - Cancer
IS - 18
ER -