CheckMate 025 randomized phase 3 study: Outcomes by key baseline factors and prior therapy for nivolumab versus everolimus in advanced renal cell carcinoma Journal Article


Authors: Escudier, B.; Sharma, P.; McDermott, D. F.; George, S.; Hammers, H. J.; Srinivas, S.; Tykodi, S. S.; Sosman, J. A.; Procopio, G.; Plimack, E. R.; Castellano, D.; Gurney, H.; Donskov, F.; Peltola, K.; Wagstaff, J.; Gauler, T. C.; Ueda, T.; Zhao, H.; Waxman, I. M.; Motzer, R. J.; on behalf of the CheckMate 025 investigators
Article Title: CheckMate 025 randomized phase 3 study: Outcomes by key baseline factors and prior therapy for nivolumab versus everolimus in advanced renal cell carcinoma
Abstract: Background The randomized, phase 3 CheckMate 025 study of nivolumab (n = 410) versus everolimus (n = 411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). Objective To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. Design, setting, and participants Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. Intervention Nivolumab 3 mg/kg every 2 wk or everolimus 10 mg once daily. Results and limitations The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age <65 and ≥65 yr; one and two or more sites of metastases; bone, liver, and lung metastases; number of prior therapies; duration of prior therapy; and prior sunitinib, pazopanib, or interleukin-2 therapy. The benefit with nivolumab versus everolimus was noteworthy for patients with poor MSKCC risk (hazard ratio 0.48, 95% confidence interval 0.32–0.70). The mortality rate at 12 mo for all subgroups was lower with nivolumab compared with everolimus. ORR also favored nivolumab. The incidence of grade 3 or 4 treatment-related adverse events across subgroups was lower with nivolumab. Limitations include the post hoc analysis and differing sample sizes between groups. Conclusion The trend for OS and ORR benefit with nivolumab for multiple subgroups, without notable safety concerns, may help to guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. Patient summary We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784. Consistent with the benefit demonstrated in previously treated patients with advanced renal cell carcinoma from CheckMate 025, an overall survival and objective response rate benefit with nivolumab versus everolimus was observed for multiple subgroups, including prognostic risk categories, age, number and sites of metastases, and prior therapies. © 2017 European Association of Urology
Keywords: adult; cancer survival; controlled study; treatment response; aged; major clinical study; overall survival; sunitinib; advanced cancer; drug safety; bone metastasis; follow up; demography; interleukin 2; randomized controlled trial; incidence; renal cell carcinoma; liver metastasis; lung metastasis; disease severity; pazopanib; open study; phase 3 clinical trial; high risk population; everolimus; clinical outcome; septic shock; phase 3; mortality rate; immune checkpoint inhibitor; nivolumab; human; male; female; priority journal; article; intestine ischemia
Journal Title: European Urology
Volume: 72
Issue: 6
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2017-12-01
Start Page: 962
End Page: 971
Language: English
DOI: 10.1016/j.eururo.2017.02.010
PROVIDER: scopus
PUBMED: 28262413
DOI/URL:
Notes: Erratum issued, see DOI: 10.1016/j.eururo.2017.12.016 -- Article -- Export Date: 2 January 2018 -- Source: Scopus
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  1. Robert Motzer
    950 Motzer