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: 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).
  
  
  
  To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus.
  
  
  
  Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model.
  
  
  
  Nivolumab 3mg/kg every 2 wk or everolimus 10mg once daily.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Gustave Roussy, Villejuif, France. Electronic address: escudier@gustaveroussy.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.affiliation: MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
authors.forename: Padmanee
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Saby
authors.initials: S
authors.lastname: George
authors.affiliation: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Hammers
authors.affiliation: Stanford Cancer Institute, Stanford, CA, USA.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Srinivas
authors.affiliation: University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Tykodi
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.affiliation: Fondazione Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procopio
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Plimack
authors.affiliation: Hospital Universitario 12 De Octubre, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.affiliation: Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Howard
authors.initials: H
authors.lastname: Gurney
authors.affiliation: Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
authors.affiliation: Comprehensive Cancer Center, Helsinki University Central Hospital Cancer Center, Helsinki, Finland.
authors.forename: Katriina
authors.initials: K
authors.lastname: Peltola
authors.affiliation: South West Wales Cancer Institute and Swansea University College of Medicine, Swansea, UK.
authors.forename: John
authors.initials: J
authors.lastname: Wagstaff
authors.affiliation: University Hospital Essen of University of Duisburg-Essen, Essen, Germany.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Gauler
authors.affiliation: Chiba Cancer Center, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Waxman
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000077594:Nivolumab; D016016:Proportional Hazards Models; D019233:Retreatment; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000074322:Antineoplastic Agents, Immunological; D000077594:Nivolumab; D000068338:Everolimus
keywords: Everolimus; Immune checkpoint inhibitor; Nivolumab; Phase 3; Renal cell carcinoma