title: Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  Response remains an important endpoint in clinical cancer trials. However, the prognostic utility of best tumor response in metastatic renal cell carcinoma (mRCC) remains vague.
  
  
  OBJECTIVE
  To define the prognostic relevance of the depth of remission in mRCC.
  
  
  METHODS
  Pooled data from the Pfizer database for 2749 patients from phase 2 and 3 clinical trials in mRCC were analyzed. Tumor shrinkage was categorized according to the best percentage change in the sum of the largest diameter of target lesions. Outcome was computed using Kaplan-Meier curves and correlation was assessed via Cox regression, including a 6-mo landmark.
  
  
  METHODS
  Sunitinib, sorafenib, axitinib, temsirolimus, or temsirolimus and interferon-α.
  
  
  METHODS
  Categorized tumor shrinkage, overall survival (OS), progression free survival (PFS).
  
  
  CONCLUSIONS
  Major tumor shrinkage of 60% or more occurred in approximately 10% of patients and was associated with median OS of 54.5 mo. OS expectations steadily decreased with depth of remission (26.4, 16.6, 10.4, and 7.3 mo). The association was maintained when stratified by type of therapy, line of therapy, and performance status. Cox proportional regression analyses for the 6-mo landmark confirmed the prognostic relevance of major tumor shrinkage (hazard ratio 0.29, 95% confidence interval 0.22-0.39; p<0.001). The major limitation of our study is the variability of imaging intervals among studies.
  
  
  CONCLUSIONS
  This is the first and largest analysis of best tumor response in mRCC. We demonstrate that depth of remission is an independent prognostic factor in mRCC.
  
  
  RESULTS
  It remains unknown whether tumor shrinkage during therapy is needed to achieve clinical activity in metastatic renal cell carcinoma. Our analysis shows that the magnitude of tumor shrinkage correlates with better survival in patients. This observation may be used as a clinical research tool in future trials.
  
  
  BACKGROUND
  NCT00054886, NCT00077974, NCT00267748, NCT00338884, NCT00137423, NCT00083889, NCT00065468, NCT00678392.
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Rana R
authors.initials: RR
authors.lastname: McKay
authors.affiliation: Department of Imaging, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Krajewski
authors.affiliation: Pfizer Oncology, Pfizer Inc., La Jolla, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kalanovic
authors.affiliation: Pfizer Oncology, Pfizer Inc., La Jolla, CA, USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Lin
authors.affiliation: Pfizer Oncology, Pfizer Inc., La Jolla, CA, USA.
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Perkins
authors.affiliation: Pfizer Oncology, Pfizer Inc., La Jolla, CA, USA.
authors.forename: Ronit
authors.initials: R
authors.lastname: Simantov
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: toni_choueiri@dfci.harvard.edu.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012074:Remission Induction / Q000379:methods; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Imaging Prognosis; Renal cell carcinoma; Targeted therapy; Tumor response; Tumor shrinkage