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Eur Urol. 2017 Dec;72(6):962-971. doi: 10.1016/j.eururo.2017.02.010. Epub 2017 Mar 3.

CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma.

Author information

1
Gustave Roussy, Villejuif, France. Electronic address: escudier@gustaveroussy.fr.
2
MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
3
Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA, USA.
4
Roswell Park Cancer Institute, Buffalo, NY, USA.
5
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
6
Stanford Cancer Institute, Stanford, CA, USA.
7
University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
8
Vanderbilt University Medical Center, Nashville, TN, USA.
9
Fondazione Istituto Nazionale Tumori, Milan, Italy.
10
Fox Chase Cancer Center, Philadelphia, PA, USA.
11
Hospital Universitario 12 De Octubre, Madrid, Spain.
12
Westmead Hospital, Westmead, NSW, Australia.
13
Aarhus University Hospital, Aarhus, Denmark.
14
Comprehensive Cancer Center, Helsinki University Central Hospital Cancer Center, Helsinki, Finland.
15
South West Wales Cancer Institute and Swansea University College of Medicine, Swansea, UK.
16
University Hospital Essen of University of Duisburg-Essen, Essen, Germany.
17
Chiba Cancer Center, Chiba, Japan.
18
Bristol-Myers Squibb, Princeton, NJ, USA.
19
Memorial Sloan Kettering Cancer Center, New York, NY, USA.

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 3mg/kg every 2 wk or everolimus 10mg 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.

KEYWORDS:

Everolimus; Immune checkpoint inhibitor; Nivolumab; Phase 3; Renal cell carcinoma

PMID:
28262413
DOI:
10.1016/j.eururo.2017.02.010
[Indexed for MEDLINE]

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