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.
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 - advanced renal cell carcinoma (aRCC)
KW - CheckMate 025
KW - everolimus
KW - immune checkpoint inhibitor
KW - nivolumab
KW - previously treated
UR - http://www.scopus.com/inward/record.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 -