title: Carbonic anhydrase IX as a potential biomarker of efficacy in metastatic clear-cell renal cell carcinoma patients receiving sorafenib or placebo: analysis from the treatment approaches in renal cancer global evaluation trial (TARGET).
abstract: OBJECTIVE
  Retrospective data analyses have suggested that carbonic anhydrase IX (CAIX) may have a predictive role in patients with metastatic clear cell renal cell carcinoma (ccRCC) receiving high dose interleukin-2 or sorafenib. We examined the predictive value of CAIX in estimating treatment outcome in patients receiving sorafenib vs. placebo as part of the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study.
  
  
  METHODS
  Paraffin embedded tumor tissues were collected from 133 patients from the TARGET study (n = 903). The percentage of CAIX-positive cells was assessed by a single pathologist. The impact of CAIX expression on progression-free survival (PFS, primary endpoint) and tumor shrinkage (TS, secondary endpoint) was analyzed.
  
  
  RESULTS
  Clinical characteristics were similarly distributed between patients with low vs. high CAIX staining, as well as patients with available CAIX data vs. not. Median PFS for patients with high CAIX vs. low CAIX expression was 5.5 and 5.4 months, respectively, on the sorafenib arm (P = 0.97), and 1.5 and 1.7 months on the placebo arm (P = 0.76). Median TS for patients with high CAIX status was -14.9% vs. -12.6% in patients with low CAIX status (P = 0.63) on the sorafenib arm, and +1.3% (high CAIX) vs. +4.8% (low CAIX) in patients on the placebo arm (P = 0.60).
  
  
  CONCLUSIONS
  Despite suggestive retrospective evidence, data from the TARGET study did not find CAIX expression status to be either predictive of clinical benefit for treatment with sorafenib or of prognostic value in patients with metastatic ccRCC following cytokine therapy.
authors.affiliation: Kidney Cancer Program, Dana-Farber/Harvard Cancer Center, Boston, MA 02215, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA; Brigham and Women's Hospital, Boston, MA 02215, USA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Suchun
authors.initials: S
authors.lastname: Cheng
authors.forename: Angela Q
authors.initials: AQ
authors.lastname: Qu
authors.forename: Jaromir
authors.initials: J
authors.lastname: Pastorek
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D007376:Interleukin-2; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: Biomarker; Carbonic anhydrase IX; Prognostic marker; Renal cell carcinoma (RCC); Sorafenib; Vascular endothelial growth factor