title: Statins and survival outcomes in patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  A growing body of evidence has demonstrated the anti-neoplastic activity of statins. The objective of this study was to investigate the effect of statin use on survival in patients with metastatic renal cell carcinoma (mRCC) treated in the modern therapy era.
  
  
  METHODS
  We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Statistical analyses were performed using Cox regression and the Kaplan-Meier method.
  
  
  RESULTS
  We identified 4736 patients treated with sunitinib (n=1059), sorafenib (n=772), axitinib (n=896), temsirolimus (n=457), temsirolimus+interferon (IFN)-α (n=208), bevacizumab+temsirolimus (n=393), bevacizumab+IFN-α (n=391) or IFN-α (n=560), of whom 511 were statin users. Overall, statin users demonstrated an improved overall survival (OS) compared to non-users (25.6 versus 18.9 months, adjusted hazard ratio [aHR] 0.801, 95% confidence interval [CI] 0.659-0.972, p=0.025). When stratified by therapy type, a benefit in OS was demonstrated in statin users compared to non-users in individuals receiving therapy targeting vascular endothelial growth factor (28.4 versus 22.2 months, aHR 0.749, 95% CI 0.584-0.961, p=0.023) or mammalian target of rapamycin (18.6 versus 14.0 months, aHR 0.657, 95% CI 0.445-0.972, p=0.035) but not in those receiving IFN-α (15.6 versus 14.8 months, aHR 1.292, 95% CI 0.703-2.275, p=0.410). Adverse events were similar between users and non-users.
  
  
  CONCLUSIONS
  We demonstrate that statin use may be associated with improved survival in patients with mRCC treated in the targeted therapy era. Statins could represent an adjunct therapy for patients with mRCC; however, this is hypothesis generating and requires prospective evaluation.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA. Electronic address: rmckay5@partners.org.
authors.forename: Rana R
authors.initials: RR
authors.lastname: McKay
authors.affiliation: Pfizer Oncology, Pfizer Inc., 235 East 42nd Street, New York, NY, 10017 USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
authors.forename: Andre P
authors.initials: AP
authors.lastname: Fay
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
authors.forename: Marina D
authors.initials: MD
authors.lastname: Kaymakcalan
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Mickey
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
authors.forename: Paiman P
authors.initials: PP
authors.lastname: Ghoroghchian
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA.
authors.forename: Rupal S
authors.initials: RS
authors.lastname: Bhatt
authors.affiliation: Department of Urology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065, USA.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Kaffenberger
authors.affiliation: Pfizer Oncology, Pfizer Inc., 235 East 42nd Street, New York, NY, 10017 USA.
authors.forename: Ronit
authors.initials: R
authors.lastname: Simantov
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Center, 1331 29 Street Northwest, Calgary, AB T2N 4N2, Canada.
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D016016:Proportional Hazards Models; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: HMG-CoA reductase inhibitors; Prognosis; Renal cell carcinoma; Statins; Targeted therapy