title: Circulating biomarkers and outcome from a randomised phase II trial of sunitinib vs everolimus for patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  RECORD-3 assessed non-inferiority of progression-free survival (PFS) with everolimus vs sunitinib in previously untreated patients with metastatic renal cell carcinoma. Baseline plasma sample collection and randomised design enabled correlation of circulating biomarkers with efficacy.
  
  
  METHODS
  Samples were analysed for 121 cancer-related biomarkers. Analyses of biomarkers categorised patients as high or low (vs median) to assess association with first-line PFS (PFS1L) for each treatment arm. A composite biomarker score (CBS) incorporated biomarkers potentially predictive of PFS1L with everolimus.
  
  
  RESULTS
  Plasma samples from 442 of the 471 randomised patients were analysed. Biomarkers were associated with PFS1L for everolimus alone (29), sunitinib alone (9) or both (12). Everolimus-specific biomarkers (CSF1, ICAM1, IL-18BP, KIM1, TNFRII) with hazard ratio ⩾ 1.8 were integrated into a CBS (range 0-5). For CBS low (0-3, n = 291) vs high (4-5, n = 151), PFS1L differed significantly for everolimus but not for sunitinib. There was no significant difference in PFS1L between everolimus and sunitinib in the high CBS patient cohort.
  
  
  CONCLUSIONS
  Baseline levels of multiple soluble biomarkers correlated with benefit from everolimus and/or sunitinib, independent of clinical risk factors. A similar PFS1L was observed for both treatments among patients with high CBS score.
authors.affiliation: Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Voss
authors.affiliation: Novartis Oncology, One Health Plaza, East Hanover, NJ 07936-1080, USA.
authors.forename: David
authors.initials: D
authors.lastname: Chen
authors.affiliation: Novartis Oncology, One Health Plaza, East Hanover, NJ 07936-1080, USA.
authors.forename: Mahtab
authors.initials: M
authors.lastname: Marker
authors.affiliation: Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA.
authors.forename: A Ari
authors.initials: AA
authors.lastname: Hakimi
authors.affiliation: Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA.
authors.forename: Chung-Han
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hsieh
authors.affiliation: Princess Margaret Cancer Center, University of Toronto, 5-210, 610 University Avenue, Toronto, Ontario M5G-2M9, Canada.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Novartis Oncology, One Health Plaza, East Hanover, NJ 07936-1080, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Voi
authors.affiliation: Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood; D000068338:Everolimus / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000097:blood* / Q000188:drug therapy*; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016207:Cytokines; D007211:Indoles; D011758:Pyrroles; D000068338:Everolimus; D000077210:Sunitinib