title: Real-world outcomes in metastatic renal cell carcinoma: insights from a Joint Community-Academic Registry.
abstract: BACKGROUND
  As new therapeutics for metastatic renal cell carcinoma (mRCC) are quickly introduced to market, comparative randomized trial evidence guiding treatment decisions is lacking, especially in the second treatment exposure and beyond. As a demonstration case, we studied mRCC in real-world clinical settings by creating a joint community-academic retrospective mRCC registry to assess outcomes.
  
  
  METHODS
  For this overall survival (OS) analysis, the analytic cohort included all patients in the registry diagnosed between January 1, 2007, to May 31, 2011 (N = 384). Patients were grouped by up to three treatment exposures according to each drug's mechanism of action: vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI), mammalian target of rapamycin inhibitor (mTOR), or no systemic treatment (NSTx, which could include radiation or surgery). OS by exposure sequence was evaluated using Kaplan-Meier, pairwise comparison, and Cox regression analyses.
  
  
  RESULTS
  Median OS was 17.2 months. OS (months) for one exposure was: mTOR 5.4, TKI 18.2, NSTx 18.4; for two exposures: mTOR/TKI 9.3, TKI/mTOR 13.9, TKI/TKI 35.2; and for three exposures: TKI/mTOR/TKI 20.9, TKI/TKI/mTOR 33.1. By pairwise comparison, OS for TKI, mTOR/TKI, TKI/mTOR, TKI/TKI, TKI/mTOR/TKI and TKI/TKI/mTOR sequences was greater than mTOR (all P < .04); demographics confirmed that individuals treated with early mTOR inhibition more commonly had adverse prognostic features. In Cox regression analysis, compared with the referent (TKI), TKI/TKI (hazard ratio = 0.53; P = .03) had a lower risk of death, and mTOR (hazard ratio = 2.16; P = .002) had a higher risk of death.
  
  
  CONCLUSIONS
  mRCC survival outcomes are different by pattern, with general findings consistent with trial-based expectations in similar patient populations. Real-world data can provide context around patterns of care and impact when experimental trial data are lacking.
authors.affiliation: Duke University Medical Center; Center for Learning Health Care, Duke Clinical Research Institute, Durham, NC; ACORN Research; Memphis, TN; and Pfizer, New York, NY.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Harrison
authors.forename: Bradford R
authors.initials: BR
authors.lastname: Hirsch
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Mark S
authors.initials: MS
authors.lastname: Walker
authors.forename: Connie
authors.initials: C
authors.lastname: Chen
authors.forename: Beata
authors.initials: B
authors.lastname: Korytowsky
authors.forename: Edward
authors.initials: E
authors.lastname: Stepanski
authors.forename: Amy P
authors.initials: AP
authors.lastname: Abernethy
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009657:North Carolina; D017063:Outcome Assessment, Health Care; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012042:Registries; D016019:Survival Analysis; D013714:Tennessee
chemical_list: D047428:Protein Kinase Inhibitors